Target	Base URL extension

Homepage	fbcv

Term request tracker	fbcv/tracker

Pre-reasoned OBO version	fbcv/dpo-simple.obo

Full OWL version	fbcv/dpo-non-classified.owl

Full details of all available versions	fbcv/downloads

Individual term details for FBcv_0000423	FBcv_0000423


Assay	Coefficient of variation

Intra-assay (%)	Inter-assay (%)

OPG	3.53	5.78

sRANKL	9.38	12.00

sRAGE	4.00	7.15

esRAGE	5.20	8.50

Assay	Coefficient of variation

Intra-assay (%)

OPG	3.53

sRANKL	9.38

sRAGE	4.00

esRAGE	5.20

Coefficient of variation

Inter-assay (%)

5.78

12.00

7.15

8.50


		Before pregnancy	1st trimester	2nd trimester	3rd trimester	6 months post-partum

Mean sexual frequency for all respondents		1.8	1.2	1.4	1.35	1.36

Circumcised females	Yes	1.8*	1.1*	1.3	1.3	1.2*

No	2.1	1.4	1.5	1.4	1.6

Episiotomy performed at delivery	Yes	—	—	—	—	1.3

No	—	—	—	—	1.2

Mode of delivery	Vaginal	—	—	—	—	1.2**

Caesarean section	—	—	—	—	2.3

Partners said to be engaged in extramarital affairs	Yes	1.5	1.1	1.0*	0.9*	1.2

No	1.9	1.2	1.5	1.4	1.4

		Before pregnancy	1st trimester	2nd trimester	3rd trimester	6 months post-partum

Mean sexual frequency for all respondents		1.8	1.2	1.4	1.35	1.36

Circumcised females	Yes	1.8*	1.1*	1.3	1.3	1.2*

No	2.1	1.4	1.5	1.4	1.6

Episiotomy p	Yes	—	—	—	—	1.3

No		—		—	1.2

erformed at delivery		—		—

Mode of delivery	Vaginal	—	—	—	—	1.2**

Caesarean section	—	—	—	—	2.3

Partners said to be engaged in extramarital affairs	Yes	1.5	1.1	1.0*	0.9*	1.2

No	1.9	1.2	1.5	1.4	1.4


	Control Group

N=51

Study period	6 m (i)	6 m (f)

Length of time (mean [SD], days)	180.2[41.8]	190.5[6.4]

Appointments

Total cost (US$) /day	8.65	6.49

Individual mean [SD] (US$)	0.17[0.08]	0.13[0.09]

Laboratory tests

Total cost (US$) /day	38.07	25.35

Individual mean [SD] (US$)	0.75[0.74]	0.50[0.46]

Procedures

Total cost (US$) /day	3.75	4.81

Individual mean [SD] (US$)	0.07[0.22]	0.09[0.21]

Hospitalization

Total cost (US$) /day	2.62	2.53

Individual mean [SD] (US$)	0.05[0.30]	0.05[0.18]

Pharmacist

Total cost (US$) /day	0.0	0.0

Individual mean [SD] (US$)	NA	NA

Total

Final cost/day (US$)	53.09	39.18

Individual mean [SD] (US$)	1.04[0.99]	0.77[0.70]

Total excluding procedures

Final cost/day (US$)	49.34	34.36

Individual mean [SD] (US$)	0.97[0.94]	0.67[0.63]


Variables	Results

Demographic variables:

 Age, years	53.3 (8.7) (28–68)

 Gender, F/M	34 (82.9)/ 7 (17)

Cardiovascular risk factors:

 Family history of CVD	20 (48.8)

 Current/Ex-smokers	23 (56.1)

 Hypertension	17 (41.5)

 Diabetes	3 (7.3)

 CKD3a (eGFR 45–59 ml/min/1.73 m2)	2 (4.9)

 AI abnormal	11 (26.8)

 BMI > 30 kg/m2	5 (12.2)

 Physical inactivity	23 (56.1)

RA related variables

 Disease duration, years	19.2 (9.2) (8–45)

 Erosions (X-ray of hands/feet)	35 (85.4)

 Extra-articular symptoms	28 (68.3)

 Positive RF-IgM	33 (80.5)

 Positive anti-CCP2	30 (73.2)

 ESR, mm/h	19.2 (16.0) (2–64)

 CRP, mg/l	14.35 (37.5) (0.1–228.5)

 Average CRP (6 years), mg/l	11.02 (9.9) (0.9–37.3)

 Low RA activity (DAS28 ≤ 3.2)	23 (56.1)

 Current glucocorticoid use	18 (43.9)

 Current conventional synthetic DMARD	39 (95.1)

 Current biological DMARD	32 (78.1)

Variables

Demographic variables:

Age, years

Gender, F/M

Cardiovascular risk factors:

Family history of CVD

Current/Ex-smokers

Hypertension

Diabetes

CKD3a (eGFR 45–59 ml/min/1.73 m2)

AI abnormal

BMI > 30 kg/m2

Physical inactivity

RA related variables

Disease duration, years

Erosions (X-ray of hands/feet)

Extra-articular symptoms

Positive RF-IgM

Positive anti-CCP2

ESR, mm/h

CRP, mg/l

Average CRP (6 years), mg/l

Low RA activity (DAS28 ≤ 3.2)

Current glucocorticoid use

Current conventional synthetic DMARD

Current biological DMARD


Source	F statistic	p	Estimated means (standard error)

Talker variability	0.505	0.481	0 4.351 (0.101) single-talker

			4.289 (0.089) multiple-talker

Talker Variability × Modality of Presentation	0.000	0.988	4.282 (0.143) audio only single-talker

			4.221 (0.125) audio only multiple-talkers

			4.420 (0.143) audio-visual single-talker

			4.357 (0.125) audio-visual multiple-talkers

Modality of presentation	0.653	0.423	4.252 (0.120) audio-only

			4.389 (0.120) audio-visual

Source	F statistic	p

Talker variability	0.505	0.481

Talker Variability × Modality of Presentation	0.000	0.988

Modality of presentation	0.653	0.423

Estimated means (standard error)

0 4.351 (0.101) single-talker

4.289 (0.089) multiple-talker

4.282 (0.143) audio only single-talker

4.221 (0.125) audio only multiple-talkers

4.420 (0.143) audio-visual single-talker

4.357 (0.125) audio-visual multiple-talkers

4.252 (0.120) audio-only

4.389 (0.120) audio-visual


Parameter

W/H

BMI

TG

Chol

LDL-C

HDL-C

VLDL-C

ApoB

ApoA1

TG/HDL-C

LDL-C/HDL-C

LDL size


	FNA

Suspected hepatic metastasis

Specific diagnosis	56%	(70/124)

∗Diagnosis malignant versus benign	93%	(115/124)

Suspected primary neoplasms

Specific diagnosis	70.5%	(43/61)

Total	85.4%	(158/185)


Patients (n = 458)

Baseline characteristics	 	% or mean	(n or SD)

Men%	 	24.9	(114)

Women%	 	74.7	(342)

Age mean years (SD)	 	54.0	(7.4)

Weight mean kg (SD)	 	96.4	(18.3)

Starting BMI mean kg/m2 (SD)	 	36.0	(5.9)

Starting BMI kg/m2%	<30	9.8	(45)

 	30-34	43.9	(201)

 	35-39	23.8	(109)

 	≥40	21.2	(97)

 	not recorded	1.3	(6)

Smoking status%	smoker	14.4	(66)

 	not recorded	18.8	(86)

Diabetes Status%	diabetic	11.6	(53)

 	not recorded	15.7	(72)

Patients (n = 458)

Baseline characteristics		% or mean	(n or SD)

Men%		24.9	(114)

Women%		74.7	(342)

Age mean years (SD)		54.0	(7.4)

Weight mean kg (SD)		96.4	(18.3)

Starting BMI mean kg/m2 (SD)		36.0	(5.9)

Starting BMI kg/m2%	<30	9.8	(45)

	30-34	43.9	(201)

	35-39	23.8	(109)

	≥40	21.2	(97)

	not recorded	1.3	(6)

Smoking status%	smoker	14.4	(66)

	not recorded	18.8	(86)

Diabetes St	diabeti	11	(


		Photographic ICDAS score UR6 occlusal

		0	2	3	4	5	6	F	S

Clinical ICDAS Score UR6 Occlusal	0	506	8	0	0	0	0	2	5

	2	252	327	26	4	2	0	7	7

	3	2	66	48	3	1	0	1	1

	4	2	25	15	25	4	0	1	1


Mean value of MI	Standard deviation of MI	Num of positive values	Num of negative values	Num of values ofdifferent sign	Min value	Max value


Complication	EN group(n = 8)	EN+PN group(n = 9)

Surgery related complications

 Pancreatic leakage (minor leakage)	0	1

 Anastomotic leakage (minor leakage)	1	0

 Ileus	1	0

 Ulcer at anastomotic portion	0	1

 Wound infection	3	1

General complications

 Pulmonary	1	0

Total number of patients with complications	5	4

Mortality	1	0

No significant differences noted.

Complication	EN group(n = 8)	EN+PN group(n = 9)

Surgery related complications

Pancreatic leakage (minor leakage)	0	1

Anastomotic leakage (minor leakage)	1	0

Ileus	1	0

Ulcer at anastomotic portion	0	1

Wound infection	3	1

General complications

Pulmonary	1	0

Total number o	5	4

f patients with complications

Mortality	1	0

No significant differences noted.


Food outlets	Accessibility/availability measures	All cases	Type 1 diabetes	Type 2 diabetes

Mean (SD)	Range	Mean (SD)	Range	Mean (SD)	Range

 food	ile buffer	1.2 (2.7)	.0	.2 (2.7)	17.0	4 (2.7)	.0

Density (number per sq. mile)	1.7 (2.0)	0.0, 9.8	1.7 (2.0)	0.0, 9.2	1.8 (2.1)	0.0, 9.8


Category	Age (years)	Hb (g/dL)	Parasite density (% of parasitized RBCs)

Complicated cases	2.384 (±1.239)	9.579 (±0.900)	10.542 (±2.704)

Uncomplicated controls	2.796 (±1.315)	12.338 (±1.278)	7.596 (±2.040)

P value	0.007	<0.0001	<0.0001


Patients/reference group	Mean	SD	Comment Original publication

MS	35.4	12.1	Present data

Stroke	42.1	12.7	Present data

Male, age 40–49	64.2	16.3	German Health Survey 1998 (20) (N = 6964 participants, age 18–80)

Male, age 50–59	61.5	18.1	German Health Survey 1998 (20)

Female, age 40–49	57.4	18.8	German Health Survey 1998 (20)

Female, age 50–59	57.7	18.8	German Health Survey 1998 (20)

Patients/reference group	Mean	SD	Comment Original publication

Female, age 40–49	57.4	18.8	German Health Survey 1998 (20)

Female, age 50–59	57.7	18.8	German Health Survey 1998 (20)


Parameter	Leaf oil 	Bark oil

Specific gravity (20°C) 	1.030–1.050 	1.010–1.030

Optical rotation (°) (20°C) 	1°96′–0°40′	Slightly laevorotatory

Refractive index (20°C) 	1.529–1.537 	1.573–1.591

Aldehyde content 	4% 	65–76%

Eugenol content 	77.3–90.5% 	4–10%

Solubility characteristics 	Soluble in 1.5 volumes of 70% alcohol 	Soluble in 2.0–3.0 volumes of 70% alcohol

Parameter	Leaf oil	Bark oil

Solubility characteristics	Soluble in 1.5 volumes of 70% alcohol	Soluble in 2.0–3.0 volumes of 70% alcohol


Degree of comfort	Attending to patients with mental illness	Dealing with mentally sick people

	Frequency	Percent	Frequency	Percent

Extremely uncomfortable	22	19.8	28	25.2

Uncomfortable	54	48.6	41	36.9

Comfortable	31	27.9	37	33.3

Extremely comfortable	4	3.6	5	4.5

TOTAL	111	100.0	111	100.0


Wafers or Bars per Day

NumTrey

Wafer

17

20

27

40

53

79

106

131

200 kcal/kg/day


	ATIC mRNA expression△	p value

Variable	Low (117)	high (117)	(chi-square)

Gender

 Male	83	81	0.8865

 Female	34	36

Diagnosis Age

≤ 50	23	30	0.3488

> 50	94	87

AFP (ng/mL)

≤ 200	97	74	0.0011*

> 200	20	43

Hepatitis status

 Negative	61	44	0.0352*

 Positive	56	73

Vascular Invasion

 No	85	69	0.0384*

 Yes	32	48

Histologic Grade

 G1	17	9	0.0006*

 G2	64	43

 G3-G4	36	65

TNM stage

 I	78	56	0.0086*

 II	24	31

 III-IV	15	30

Variable

Gender

Male

Female

Diagnosis Age

≤ 50

> 50

AFP (ng/mL)

≤ 200

> 200

Hepatitis status

Negative

Positive

Vascular Invasion

No

Yes

Histologic Grade

G1

G2

G3-G4

TNM stage

I

II

III-IV


Subset	Reference range	Probands	Goodness of fit	Spouses	Goodness of fit

	% subset sum	% below	% within	% above	p-value*	% below	% within	% above	p-value


Residue	pKa	Buried (%)	Desolvation effects	Hydrogen bond	Coulombic interaction	Atoms cofactor

			Regular	RE	Side chain	Backbone

Tyr345 G	11.99	56 %	0.90 438	0.00 0	0.21 Asp315 G		–0.02 Arg3180.90 Asp315

	2.6	97	3.82 55	1.17 0	–1.60 His313 G–0.85 Lys319 G	–0.	–0.10 Arg318–0.32 His316–1.13 	=>N3


Component	Changes in SLE T cells	Reference

TCRζ

	Decreased TCRζ expression/phosphorylation	Grammatikos et al. (26), Kyttaris et al. (27), Pang et al. (29), and Takeuchi et al. (28)

	3′ UTR variants leading to instable versions of TCRζ	Chowdhury et al. (30), Gorman et al. (31), and Tsuzaka et al. (32)

Syk

	Replaces canonical ZAP-70	Krishnan et al. (33) and Tanaka et al. (34)

	More potent signal transduction	Tanaka et al. (34)

	Increased expression: inability of CREMα to repress transcription	Ghosh et al. (35)

Calcium signaling

	Increased recruitment of NFATc2 into the nucleus	Kyttaris et al. (36)

→ Elevated expression of CD154

	Enhanced nuclear import of CAMK IV	Juang et al. (37)

→ Elevated expression of CREMα

Other signaling components

	LAT displaced from lipid rafts	Abdoel et al. (38)

	Aberrant phosphorylation of Erk	Cedeno et al. (39) and Yi et al. (40)

Genes identified by GWAS

	UBASH3A	Diaz-Gallo et al. (41)

PP2AC	Katsiari et al. (42), and Tan et al. (43)

	TNFAIP3	Graham et al. (44)

SLAM	Morel et al. (45)

Component

TCRζ

Syk

Calcium signaling

Other signaling components

Genes identified by GWAS


Variable	Mean (SD)	Range

Age (years)	65.6 (9.5)	49 – 80

Duration of disease (years)	14.3 (5.7)	5 – 23


	Antibiotic class

Strains	Carb-apenem	Cephalo-sporin	Aminogly-coside	Fluoro-quinolone

Antibiotics*	IPM	CFP	CAZ	GM	CIP

ATCC 27853	29	30	33	21	34

1	29	22	28	21	28

3	12	25	28	21	24

6	34	28	33	23	32

11	30	28	30	21	32

19	28	0	0	0	0

2			0	9


		No. of patients (%)

Variable	Total	KLK5- negative KLK5- positive	p value

> 5 cm	4	3 (75.0)	1 (25.0)

ER status

Negative	16	7 (43.8)	9 (56.3)	0.028b

Positive	51	39 (76.5)	12 (23.5)

PR status

Negative	24	15 (62.5)	9 (37.5)	0.42b

Positive	43	31 (72.1)	12 (27.9)


Days	Scenario 1	Scenario 2	Scenario 3	Scenario 4	Scenario 5	Scenario 6	Scenario 7

1	●	●	●	●	●	●	●

2	●	●	●	●	●	●	●

3	●	● (± α h)	○	●	●1	●	●

4	●1	●1	●	●1	●1	○	● (+ 4 h)1

5	●1	●1	●	● (± β h)1	●1	●1	●1

6	●1	●1	●1	●1	○1	●1	●1

n	24	24	24	24	24	24	72

t (h)	24	24	24	24	24	24	72 (-4)

ni (X-ray)	70	52	24	60	69 (+24)	48	65

CTT (h)	70	52	24	60	93	48	61.4

Days	Scenario 1	Scenario 2	Scenario 3	Scenario 4	Scenario 5	Scenario 6

1	●	●	●	●	●	●

2	●	●	●	●	●	●

3	●	● (± α h)	○	●	●1	●

4	●1	●1	●	●1	●1	○

5	●1	●1	●	● (± β h)1	●1	●1

6	●1	●1	●1	●1	○1	●1

n	24	24	24	24	24	24

t (h)	24	24	24	24	24	24

ni (X-ray)	70	52	24	60	69 (+24)	48

CTT (h)	70	52	24	60	93	48


Feature	Wheeled Vehicle	Tracked Vehicle	Low-Altitude Helicopter

Car	Truck	SUV	Van

Weight (kg)	1,425	6,800	1,635	1,713	40,200	3,850

Number of Cylinders	4	6	4	5	10	8

Engine Capacity	78	170	110	140	3,240	1,468

Feature	Car	Truck	SUV	Van	Tracked Vehicle	Low-Altitude Helicopter

Weight (kg)	1,425	6,800	1,635	1,713	40,200	3,850

Number of Cylinders	4	6	4	5	10	8

Engine Capacity	78	170	110	140	3,240	1,468


 	Recognition rates (%)

Method	No. of training samples	Average recognition rates (%)

 	3	4

GWT	79.65	82.5	81.1

KDCV	69.5	75	72.25

GWT-LDA	82.76	85.33	84.1

GWT-KDCV (RBF)	81	82.50	81.75

GWT-KDCV (Cosine)	83	85	84.5

GWT-KDCV (RBF, low-energized)	88.5	91.5	90

GWT-KDCV (Cosine, low-energized)	92.5	95.75	94.1

	Recognition rates (%)

Method	No. of training samples

	3	4

GWT	79.65	82.5

KDCV	69.5	75

GWT-LDA	82.76	85.33

GWT-KDCV (RBF)	81	82.50

GWT-KDCV (Cosine)	83	85

GWT-KDCV (RBF, low-energized)	88.5	91.5

GWT-KDCV (Cosine, low-energized)	92.5	95.75


Technique	Description	Metrics	Evidence of changes in trauma	Population

Time domain	Estimation of variability using statistics and measures of central tendency [3]	HRVi	↓ predicts mortality, ICH, adrenal insufficiency [11, 15, 19–22, 36]	ICU

Uncoupling	↑ reflects acidosis, coagulopathy, MOSF, AI, severe TBI, ↑ ICP, predicts mortality [6, 9, 12, 22]	ICU

SDNN	↓ predicts TBI, mortality, acidosis, LSI [16, 23]	PrehospitalERICU

RMSSD	↓ reflects TBI, hemorrhage, mortality [23, 28, 47]	ERICU

Frequency domain	Calculation of power (amplitude) of contributing frequencies to an underlying signal [18]	TP	↓ reflects ↑ICP, TBI, prolonged neurologic recovery, need for LSI, mortality, brain death [10, 28, 43]	ICUOutpatient

LF	↓ reflects ↑ICP, TBI, hemorrhage, need for LSI, mortality, brain; ↑ reflects ↑CI, HR, MAP death [4, 10, 27, 28, 37, 43, 48, 49].	ERICU

HF	↓ reflects trauma, ↑ICP, need for LSI, hemorrhage, brain death, and mortality [10, 37, 43, 47, 50, 51]	Prehospital

LF/HF	↑ reflects ↑ICP, ↓CPP; ↓ reflects brain death, mortality, hemorrhage, ↓GCS, poor neurologic outcome [5, 7, 10, 27, 48, 51]	PrehospitalICU

Entropy	Measurement of overall disorder, randomness, or irregularity of a physiologic signal [18]	MSE	↓ predicts mortality [13, 35, 36, 45]	ICU

ApEn	↓ reflects trauma, burn, hemorrhage, brain death, and ↑ICP, MOSF, predicts mortality; ↑ reflects resuscitation [8, 14, 25, 29, 34, 37, 52]	Prehospital

SampEn	↓ reflects trauma, mortality, burn, and hemorrhage;↑ reflects resuscitation; predicts LSI [8, 25, 43]	Prehospital

FDCL	↓ reflects hemorrhage; ↑ reflects resuscitation;↓ predicts LSI [17]	Prehospital

FDDA	↓ reflects need for LSI, hemorrhage, mortality [8, 25, 43]	Prehospital

DFA	↓ reflects mortality; predicts LSI [8, 25, 43]	Prehospital

SOD	↑ reflects need for LSI, mortality [8, 25, 43]	Prehospital

StatAv	↓ reflects mortality [25]	Prehospital

Technique	Description	Metrics	Evidence of changes in trauma	Population

Time domain	Estimation of variability using statistics and measures of central tendency [3]	SDNN	↓ predicts TBI, mortality, acidosis, LSI [16, 23]	PrehospitalERICU

RMSSD	↓ reflects TBI, hemorrhage, mortality [23, 28, 47]	ERICU

Frequency domain	Calculation of power (amplitude) of contributing frequencies to an underlying signal [18]	TP	↓ reflects ↑ICP, TBI, prolonged neurologic recovery, need for LSI, mortality, brain death [10, 28, 43]	ICUOutpatient

LF	↓ reflects ↑ICP, TBI, hemorrhage, need for LSI, mortality, brain; ↑ reflects ↑CI, HR, MAP death [4, 10, 27, 28, 37, 43, 48, 49].	ERICU

HF	↓ reflects trauma, ↑ICP, need for LSI, hemorrhage, brain death, and mortality [10, 37, 43, 47, 50, 51]	Prehospital

LF/HF	↑ reflects ↑ICP, ↓CPP; ↓ reflects brain death, mortality, hemorrhage, ↓GCS, poor neurologic outcome [5, 7, 10, 27, 48, 51]	PrehospitalICU

Entropy	Measurement of overall disorder, randomness, or irregularity of a physiologic signal [18]	MSE	↓ predicts mortality [13, 35, 36, 45]	ICU

ApEn	↓ reflects trauma, burn, hemorrhage, brain death, and ↑ICP, MOSF, predicts mortality; ↑ reflects resuscitation [8, 14, 25, 29, 34, 37, 52]	Prehospital

SampEn	↓ reflects trauma, mortality, burn, and hemorrhage;↑ reflects resuscitation; predicts LSI [8, 25, 43]	Prehospital

FDCL	↓ reflects hemorrhage; ↑ reflects resuscitation;↓ predicts LSI [17]	Prehospital

FDDA	↓ reflects need for LSI, hemorrhage, mortality [8, 25, 43]	Prehospital

DFA	↓ reflects mortality; predicts LSI [8, 25, 43]	Prehospital

SOD	↑ reflects need for LSI, mortality [8, 25, 43]	Prehospital

StatAv	↓ reflects mortality [25]	Prehospital


Probe Name	Gene	Log Rank P-value for 2 groups (median split)

merck_NM_001216_at_CA9	CA9	0.03*

merck2_DQ892208_at_CA9	CA9	0.04*

merck_NM_001218_s_at_CA12	CA12	<0.01*

merck_AK096845_a_at_CA12	CA12	<0.0001*

merck2_BC087838_at_CA12	CA12	<0.01*

merck_NM_001017978_s_at_CXorf61	CXorf61	<0.01*

merck_BX538327_at_DSG3	DSG3	0.53

merck_NM_001944_a_at_DSG3	DSG3	0.33

merck2_M76482_at_DSG3	DSG3	0.48

merck_NM_001447_at_FAT2	FAT2	0.78

merck_NM_023915_s_at_GPR87	GPR87	0.15

merck_NM_032551_s_at_KISS1R	KISS1R	0.94

merck_NM_014400_at_LYPD3	LYPD3	0.03*

merck_NM_014331_at_SLC7A11	SLC7A11	<0.01*

merck_AI924527_a_at_TMPRSS4	TMPRSS4	0.75

merck2_NM_001083947_at_TMPRSS4	TMPRSS4	0.41

merck2_NM_183247_a_at_TMPRSS4	TMPRSS4	0.93


	Weeks postinfection

	4	7	10

	Control rats	Infected rats	Control rats	Infected rats	Control rats	Infected rats

TAS mol/g tissue	110.6 ± 6.5	93.5 ± 7.3a	108.2 ± 6.9	91.4 ± 7.5a	112.5 ± 6.1	98.8 ± 7.7a

	Weeks postinfection

	4	7

	Control rats	Infected rats	Control rats

TAS mol/g tissue	110.6 ± 6.5	93.5 ± 7.3a	108.2 ± 6.9

Weeks postinfection

7	10

Infected rats	Control rats	Infected rats

91.4 ± 7.5a	112.5 ± 6.1	98.8 ± 7.7a


KEGG category	Distinct ECs	ECs found in the data (% abundance)	N° of matches

Energy metabolism	173	92 (53.5%)	3,857

Carbon fixation	25	21 (84%)	986

Methane metabolism	33	12 (36.4%)	202

Nitrogen metabolism	58	30 (51.7%)	739

Oxidative phosphorylation	17	09 (52.9%)	972

Photosynthesis	03	01 (33%)	168

Redutive carboxylate cycle (CO2 fixation)	13	13 (100%)	531

Sulfur metabolism	30	12 (40%)	267

Biodegradation of Xenobiotics	217	66 (30.4%)	2,495

DDT degradation	10	03 (30%)	74

1,2-Dichloroethane degradation	05	04 (80%)	85

1,4-Dichlorobenzene degradation	22	06 (27.3%)	74

2,4-Dichlorobenzoate degradation	29	03 (10.3%)	18

3-Chloroacrylic acid degradation	04	04 (100%)	185

Atrazine degradation	12	04 (33.3%)	24

Benzoate degradation via CoA ligation	45	23 (51%)	994

Benzoate degradation via hydroxylation	50	18 (36%)	158

Biphenyl degradation	13	03 (23.1%)	71

Caprolactam degradation	22	10 (45.5%)	131

Carbazole degradation	11	01 (9.1%)	03

Ethylbenzene degradation	09	03 (33.3%)	207

Fluorene degradation	13	03(23.1%)	64

Naphthalene and anthracene degradation	21	03 (14.3%)	188

Styrene degradation	21	09 (42.9%)	73

Tetrachloroethene degradation	07	01 (14.3%)	57

Toluene and xylene degradation	22	07 (31.8%)	32

γ-Hecachlorocyclohexane degradation	24	07 (29.2%)	57

Carbohydrate metabolism	576	284 (49.3%)	9,901

Aminosugars metabolism	41	25 (61%)	589

Ascorbate and aldarate metabolism	43	18 (41.9%)	367

Butanoate metabolism	53	34 (64.2%)	1,802

C5-Branched dibasic acid metabolism Fructose	17	03 (17.6%)	126

and mannose metabolism	66	28 (42.4%)	591

Galactose metabolism	37	19 (51.4%)	529

Glycolysis/Gluconeogenesis	42	29 (69%)	858

Glyoxylate and dicarboxylate metabolism	58	30 (51.7%)	676

Inositol metabolism	09	07 (77.8%)	90

Inositol phosphate metabolism	30	05 (16.4%)	34

Nucleotide sugars metabolism	34	18 (52.9%)	517

Pentose and glucuronate interconversions	56	27(48.2%)	229

Pentose phosphate pathway	39	31 (79.5%)	846

Propanoate metabolism	49	34 (69.4%)	1032

Pyruvate metabolism	65	39 (60%)	1,117

Starch and sucrose metabolism	73	33 (45.2%)	498


Name	Descriptions	Reference

Bacterial strains

E. coli BL21 (DE3)	F-, dcm, ompT, gal, lon, hsdSB (rB−, mB−), λ (DE3[lacI, lacUV5-T7 gene 1, ind1, sam7,nin5])	Lab stock

J3	E. coli BL21 (DE3) harboring rbcLS-pET30a + (M259T)	[15]

JB	E. coli BL21 (DE3) harboring both PBAD-his6-prkA-pACYC184 and rbcLS-pET30a + (M259T)	[15]

MZ	E. coli BL21 (DE3) Δzwf	[16]

MZL	MZ, Δldh	This study

MZLF	MZL, Δfrd	This study

MZLF1	MZLF harboring PBAD-his6-prkA-pACYC184	This study

MZLF3	MZLF harboring rbcLS-pET30a + (M259T)	This study

MZLFB	MZLF harboring both PBAD-his6-prkA-pACYC184 and rbcLS-pET30a + (M259T)	This study

Plasmids

pKD46	araC, bla, oriR101, repA101 (Ts), araC-ParaB-γ-β-exo (encode λ Red recombinases), temperature-conditional replicon	[30]

pkD13	bla, FRT-kan-FRT	[30]

pCP20	FLP+, λ cI857+,λ PR Pepts, bla, catF	[31]

PBAD-his6-prkA-pA CYC184	Recombinant plasmid carries prkA gene (derived from Synechococcus PCC7492) for the overexpresion of phosphoribulokinase (PrkA) under the control of PBAD	[13]

rbcLS-pET30a + (M259T)	Recombinant plasmid carries engineered rbcLS gene (originated from Synechococcus PCC6301) for the overexpresion of engineered Rubisco (M259T) under the control of PT7	[13]

rbcLS-pET30a + (M259T, K198G)	Recombinant plasmid carries engineered rbcLS gene (originated from Synechococcus PCC6301) for the overexpresion of engineered Rubisco (M259T and K198G) under the control of PT7	This study

rbcLS-pET30a + (M259T, K198G, D200G, E201G)	Recombinant plasmid carries engineered rbcLS gene (originated from Synechococcus PCC6301) for the overexpresion of engineered Rubisco (M259T, K198G, D200G, and E201G) under the control of PT7	This study

rbcLS-pET30a + (M259T, K198G, K172G)	Recombinant plasmid carries engineered rbcLS gene (originated from Synechococcus PCC6301) for the overexpresion of engineered Rubisco (M259T, K198G, and K172G) under the control of PT7	This study

rbcLS-pET30a + (M259T, K198G, K331G)	Recombinant plasmid carries engineered rbcLS gene (originated from Synechococcus PCC6301) for the overexpresion of engineered Rubisco (M259T, K198G, and K331G) under the control of PT7	This study


	GPA score	SIR score	BSBM score

	0	0.5	1	0	1	2	0	1

Age	≥60	51-59	≤50	≥60	51-59	≤50	NA

KPS	<70	70-80	90-100	≤50	60-70	>70	50-70	80-100

Control of primary cancer	NA	PD	PR-SD	CR-NED	No	Yes

Volume of the largest BM (cc)	NA	>13	5-13	<5	NA

No. of BM	>3	2-3	1	≥3	2	1	NA

EC metastasis	(+)		(−)	NA	(+)	(−)

	GPA score	SIR score	BSBM score

	0	0.5	1	0	1	2	0	1

KPS	<70	70-80	90-100	≤50	60-70	>70	50-70	80-100

Control of primary cancer	NA	PD	PR-SD	CR-NED	No	Yes

Volume of the largest BM (cc)	NA	>13	5-13	<5	NA

No. of BM	>3	2-3	1	≥3	2	1	NA

EC metastasis	(+)		(−)	NA	(+)	(−)


Screening tool	Positive result	Sensitivity	Specificity	Study Populations

 	 	(95% CI)	(95% CI)

AUDIT-C	≥ 4 (men)	86 (80-92) men	89 (85-93) men	Primary care [24]

(3 items)*	≥ 3 (women)	73 (66-79) women	91 (89-93) women

Quantity-Frequency	Exceeding recommended	88 (83-94) men	84 (80-89) men	Primary care [24]

(3 items)*	drinking limits	68 (61-75) women	91 (89-93) women

Heavy-drinking day	Any heavy days (≥ 4 drinks women, ≥ 5 drinks men)	83 (71-90) men	72 (61-81) men	Primary care [27]

past year (1 item)	 	81 (64-91) women	84 (76-89) women

Screening tool	Positive result	Sensitivity	Specificity	Study Populations

		(95% CI)	(95% CI)

(3 items)*	≥ 3 (women)	73 (66-79) women	91 (89-93) women	Primary care [24]

Quantity-Frequency	Exceeding recommended	88 (83-94) men	84 (80-89) men	Primary care [24]

(3 items)*	drinking limits	68 (61-75) women	91 (89-93) women

Heavy-drinking day	Any heavy days (≥ 4 drinks women, ≥ 5 drinks men)	83 (71-90) men	72 (61-81) men	Primary care [27]

past year (1 item)		81 (64-91) women	84 (76-89) women


Treatment	ctb	csb	del	r	cf	ra	Total aberrationsa

Solvent control : Tween-80 (1%)	-	1	-	6	6	-	13 ± 0.58

Methyl methansulfonate (MMS)	-	16	-	17	12	-	44 ± 3.06

TOF enriched extract	-	3	-	3	3	-	9 ± 1.53

Aqueous extract	-	4	-	4	2	-	10 ± 0.62

Methanolic extract	-	-	-	3	11	-	14 ± 0,58

Solvent control : Tween-80 (5%)	-	-	-	10	7	-	17 ± 1.15

Ethyl acetate extract	-	2	-	12	5	-	19 ± 1.53


Ingredient	Control Cream	Test Cream

Xyliance	4%	4%

Kendi oil	0.5%	0.5%

Phenoxyethanol	0.5%	0.5%

Aqua	QS	QS

Rhodosorus marinus extract/Dexamethasone		1% or 3%/0.2%

Ingredient	Control Cream	Test Cream

Xyliance	4%	4%

Kendi oil	0.5%	0.5%

Phenoxyethan	0.5	0.5

Ingredient	Control Cream	Test Cream

ol	%	%

Aqua	QS	QS

Rhodosorus marinus extract/Dexamethasone		1% or 3%/0.2%


Parameters	Respondents	Mbarali district (%)	Momba district (%)	p value

Age of household head (years)

 15-30	120	1.7	11.7	0.013

 31-45	120	52.5	45

 46-60	120	35	29.2

 >60	120	10.8	14.2

Experience of keeping cattle (years)

 <5	120	1.7	11.7	0.005

 5-10	120	35	37.5

 >10	120	63.3	50.8

Level of education of the household head

 No formal education	120	0.8	25	<0.0001

 Primary education	120	80	65

 Secondary education	120	19.2	9.2

 College education	120	0	0.8

Land owned by the household

 <5 acres	120	3.3	15.8	0.01

 5-10 acres	120	36.7	34.2

 11-50 acres	120	57.5	46.7

 >50 acres	120	2.5	3.3

Number of cattle raised by the household

 <10 cattle	120	3.3	34.2	<0.0001

 10-50 cattle	120	68.3	59.2

 >50 cattle	120	28.3	6.7

Parameters	Respondents	Mbarali district (%)	Momba district (%)	p value

Level of education of the household head

No formal education	120	0.8	25	<0.0001

Primary education	120	80	65

Secondary education	120	19.2	9.2

College education	120	0	0.8

Land owned by the household

<5 acres	120	3.3	15.8	0.01

5-10 acres	120	36.7	34.2

11-50 acres	120	57.5	46.7

>50 acres	120	2.5	3.3

Number of cattle raised by the household

<10 cattle	120	3.3	34.2	<0.0001

10-50 cattle	120	68.3	59.2

>50 cattle	120	28.3	6.7


	Delusions of guilt	Delusions of grandiosity	Persecutory delusions	Somatic delusions	None of these delusional types

Schizophrenia	2 (1.7%)	7 (6.0%)	33 (28.4%)	7 (6.0%)	76 (75.5%)

Delusional disorder	0	1 (2.4%)	21 (50.0%)	3 (7.1%)	19 (45.2%)

Schizoaffective disorder, manic type	0	2 (22.2)	1 (11.1%)	0	6 (66.7%)

Schizoaffective disorder, mixed type	0	0	1 (14.3%)	1 (14.3%)	5 (71.4%)

Schizoaffective disorder, depressive type	2 (8.3%)	0	4 (16.7%)	0	18 (75.0%)

Bipolar I disorder, current episode manic	0	16 (21.6)	7 (9.5%)	1 (1.4%)	54 (73.0%)

Bipolar I disorder, current episode mixed	1 (9.1%)	1 (9.1%)	3 (27.3%)	1 (9.1%)	7 (63.6%)

Bipolar disorder, current episode depressed with psychotic features	6 (42.9%)	0	6 (42.9%)	4 (28.6%)	3 (21.4%)

Major depressive disorder with psychotic features	24 (47.1%)	0	3 (5.9%)	6 (11.8%)	22 (43.1%)

Between-group differences	MDD > all other groups except BD and BM (p < 0.001)BD > all other groups except BM and SAD (p < 0.01)	M > MDD and SC (p < 0.001)SAMA > MDD (p < 0.05)	SC (p < 0.05), DD (p < 0.01), and BD (p < 0.05) > MDDDD (p < 0.01) and BD (p < 0.05) > M	BD > M (p < 0.01)

	Delusions of guilt	Delusions of grandiosity	Persecutory delusions	Somatic delusions	None of these delusional types

Major depressive disorder with psychotic features	24 (47.1%)	0	3 (5.9%)	6 (11.8%)	22 (43.1%)

Between-group differences	MDD > all other groups except BD and BM (p < 0.001)BD > all other groups except BM and SAD (p < 0.01)	M > MDD and SC (p < 0.001)SAMA > MDD (p < 0.05)	SC (p < 0.05), DD (p < 0.01), and BD (p < 0.05) > MDDDD (p < 0.01) and BD (p < 0.05) > M	BD > M (p < 0.01)


Item	Common themes	Groups	Quotes

Description and causes of fatigue.	Overwhelming physical tiredness with consequences on difficulties to move	Common in all groups: RA, AxSpA and fibromyalgia	I feel that my body is broken and every movement is as if I was moving a mountain

The need to rest more	RA and fibromyalgia	In the morning when I see my kids, I already feel tired and I even feel that I did not want to wake up

A sense of freezing of the body	AxSpA	When I have fatigue, my body is wooden and I move with difficulty

A toxin in the body	RA and AxSpA	It is toxic in my body, everything becomes difficult

Fatigue and pain	Close association between fatigue and pain	Common in all groups: RA, AxSpA and fibromyalgia

Daily patterns of fatigue	Fatigue is more in the morning	AxSpA	When I get up I feel that I am very tired and I wait for one hour to be able to move

Fatigue is more in the evening	RA, AxSpA	At the end of the day when I have finished my tasks I feel that my body is broken

No special daily patterns	Fibromyalgia

Consequences of fatigue	Fatigue affected physical activity to the extent that participants did their work only minimally	Common in all groups: RA, AxSpA and fibromyalgia	I do important things only

Social activities became limited to the close family and to very important occasions.	RA and fibromyalgia (female only)	I go to weddings and condolence gatherings only, because of my fatigue

Fatigue affected leisure activities markedly	RA and fibromyalgia	I forget what leisure means

	A difficulty in reaching the place of work	Common in all groups: RA, AxSpA and fibromyalgia	I can hardly walk to my work though it is only about 30 min

	Women told their husbands to marry again	RA and fibromyalgia	I asked my husband to marry again, he needs a healthy woman and I am too tired

	A decrease in male sexual activity	AxSpA	I get fatigued easily and this is a problem for my sexual life

Coping strategies	Dividing big tasks into smaller multiple tasks	Common in all groups: RA, AxSpA and fibromyalgia

	Getting help from family members	RA	My mother and sisters help me to complete my daily tasks

Item	Common themes	Groups

Description and causes of fatigue.	Overwhelming physical tiredness with consequences on difficulties to move	Common in all groups: RA, AxSpA and fibromyalgia

The need to rest more	RA and fibromyalgia

A sense of freezing of the body	AxSpA

A toxin in the body	RA and AxSpA

Fatigue and pain	Close association between fatigue and pain	Common in all groups: RA, AxSpA and fibromyalgia

Daily patterns of fatigue	Fatigue is more in the morning	AxSpA

Fatigue is more in the evening	RA, AxSpA

No special daily patterns	Fibromyalgia

Consequences of fatigue	Fatigue affected physical activity to the extent that participants did their work only minimally	Common in all groups: RA, AxSpA and fibromyalgia

Social activities became limited to the close family and to very important occasions.	RA and fibromyalgia (female only)

Fatigue affected leisure activities markedly	RA and fibromyalgia

	A difficulty in reaching the place of work	Common in all groups: RA, AxSpA and fibromyalgia

	Women told their husbands to marry again	RA and fibromyalgia

	A decrease in male sexual activity	AxSpA

Coping strategies	Dividing big tasks into smaller multiple tasks	Common in all groups: RA, AxSpA and fibromyalgia

	Getting help from family members	RA

Quotes

I feel that my body is broken and every movement is as if I was moving a mountain

In the morning when I see my kids, I already feel tired and I even feel that I did not want to wake up

When I have fatigue, my body is wooden and I move with difficulty

It is toxic in my body, everything becomes difficult

When I get up I feel that I am very tired and I wait for one hour to be able to move

At the end of the day when I have finished my tasks I feel that my body is broken

I do important things only

I go to weddings and condolence gatherings only, because of my fatigue

I forget what leisure means

I can hardly walk to my work though it is only about 30 min

I asked my husband to marry again, he needs a healthy woman and I am too tired

I get fatigued easily and this is a problem for my sexual life

My mother and sisters help me to complete my daily tasks


Cluster	TRANSFAC Annotations

A	V$POU3F2_02

	V$ISRE_01: interferon-stimulated response element

	V$DEAF1_01

	V$E2F1_Q3_01

	V$MAZR_01: MAZ related factor

	V$KROX_Q6

	V$E2F1DP1_01: E2F-1:DP-1 heterodimer

	V$HNF1_Q6

	V$E2F_Q3_01

	V$E2F1_Q6: E2F-1

Cluster	Common GO Parent Node	Gene Ontology	GO Level	GO Name

B	signal transduction [4] GO:0007165	GO:0007264	6	small GTPase mediated signal transduction

		GO:0007165	4	signal transduction

		GO:0007242	5	intracellular signaling cascade

C	programmed cell death [5] GO:0012501	GO:0006917	8	induction of apoptosis

		GO:0012502	7	induction of programmed cell death

		GO:0043068	6	positive regulation of programmed cell death

		GO:0043065	7	positive regulation of apoptosis

		GO:0050794	3*	regulation of cellular process

		GO:0016265	3*	death

		GO:0008219	4*	cell death

		GO:0012501	5	programmed cell death

		GO:0006915	6	apoptosis

		GO:0043067	5	regulation of programmed cell death

		GO:0042981	6	regulation of apoptosis

D	response to stress [4] GO:0006950	GO:0006950	4	response to stress

E	macromolecule metabolic process [4] GO:0043170	GO:0006493	9	O-linked glycosylation

		GO:0043170	4	macromolecule metabolism

		GO:0044260	5	cellular macromolecule metabolism

		GO:0019222	4*	regulation of metabolism

F	transcription [6] GO:0006350	GO:0006350	6	transcription

		GO:0045449	6	regulation of transcription

		GO:0019219	5*	regulation of nucleo-base, -side, -tide and nucleic acid metabolism

		GO:0006355	7	regulation of transcription, DNA-dependent

		GO:0006351	7	transcription, DNA-dependent

G	cell cycle process [6] GO:0022402	GO:0000082	7	G1/S transition of mitotic cell cycle

		GO:0000132	11	mitotic spindle orientation

H	mevalonate transport [8] GO:0015728	GO:0015728	8	mevalonate transport


Age in years (Mean ± SD)	30.4 ± 7.7

Gender# (%)	Female2,144 (44.5%)	Male2,675 (55.5%)

Residency Year# of residents	R1 = 1,638	R2 = 1,578	R3 = 1,152


Neonate causes	Level 1	Level 2A	Level 2B

Birth asphyxia	461	0	0

Congenital malformation	250	0	0

Meningitis (serious infection)	6	0	0

Pneumonia (serious infection)	84	5	0

Preterm delivery (<33 weeks gestational age [GA]) without respiratory distress syndrome (RDS)	353	0	0

Preterm delivery (with or without RDS) and sepsis	75	1	0

Preterm delivery (without RDS) and birth asphyxia	89	0	0

Preterm delivery (without RDS) and sepsis and birth asphyxia	34	0	0

Respiratory distress syndrome (33-36 weeks GA)	13	0	0

Respiratory distress syndrome (<33 weeks GA)	97	0	0

Sepsis (serious infection)	127	1	0

Sepsis with local bacterial infection	32	1	0

Stillbirth	1,001	1	0

Tetanus	4	0	0

Neonate causes	Level 1	Level 2A	Level 2B

Sepsis with local bacterial infection	32	1	0

Stillbirth	1,001	1	0

Tetanus	4	0	0


Clinical group	Age at diagnosis(mean and range)	Preexisting cardiovascular disease/hypertension	Preexisting type II diabetes	Smoker/exsmoker 	Mean follow-up time posttreatment (years)	Mean time to onset of Grade 3 proctitis (range)

Control	69 (60–77)	8/20	3/20	8/20	6	N/A

Radiosensitive	73 (68–76)	6/10	1/10	4/10	7	21 months(9–41 months)


Group	Protein length (aa)	Exon number	Exon length (nt)

Mean	Median	K	Mean	Median	K	Mean	Median	K

Alveolata	535	364	e	3.6	2	i	449	161	h

Amoebozoa	463	351	f	3.1	2	j	448	192	f

Chlorophyta	490	369	e	5.4	3	g	270	139	j

Choanoflagellida	648	459	b	8.2	6	b	237	113	m

Cryptophyta	435	316	h	6.5	5	c	199	82	n

Excavata	471	334	g	1.1	1	m	1330	935	a

Fungi	462	381	d	3.3	2	k	421	195	e

Haptophyta	367	294	i	3.7	3	h	295	164	g

Ichthyosporea	637	494	a	4.8	4	d	398	152	i

Metazoa	595	439	c	10.1	7	a	176	126	l

Nucleariida	690	499	a	4.8	4	e	429	216	c

Rhodophyta	411	334	g	1.9	1	n	665	330	b

Stramenopila	467	356	f	3.5	2	l	399	196	d

Streptophyta	436	363	f	5.7	4	f	230	128	k


Model	Bayes factor

40° Head orientation

Body orientation + hemifield	1

All other models	>100

20° Head orientation

Body orientation + hemifield	1

Body orientation * hemifield	22

All other models	>100

Model	Bayes factor

40° Head orientation

Model	Bayes factor

Body orientation + hemifield	1

All other models	>100

20° Head orientation

Body orientation + hemifield	1

Body orientation * hemifield	22

All other models	>100


 	UEBMI	URBMI

 	Insured	Uninsured	Insured	Uninsured

Dependent variable

 Outpatient visit rate (%)	13.02	7.69	12.74	7.93

 Inpatient visit rate (%)	6.11	5.52	4.68	2.99

Need variables

 Female	47.3	50.5	58.5	58.5

 45-59	34.1	36.7	23.5	23.0

 60+	16.8	15.0	16.4	16.5

 Health status	79.2	80.2	81.5	81.9

 Illness	12.9	12.8	12.3	10.2

 Chronic disease	16.6	17.0	18.7	16.0

Control variables

 Annual personal expenditure	7192	7322	6840	7026

 Married	82.6	81.9	63.5	61.5

 Other married status	8.5	8.3	10.8	11.6

 Commercial health insurance	5.1	4.3	4.7	4.0

 Household population	3.5	3.6	3.5	3.5

 Distance to the nearest health institution	10.0	8.8	9.8	9.5

	UEBMI	URBMI

	Insured	Uninsured	Insured	Uninsured

Dependent variable

Outpatient visit rate (%)	13.02	7.69	12.74	7.93

Inpatient visit rat	6		4.68

	UEBMI	URBMI

	Insured	Uninsured	Insured	Uninsured

e (%)	.11	5.52		2.99

Need variables

Female	47.3	50.5	58.5	58.5

45-59	34.1	36.7	23.5	23.0

60+	16.8	15.0	16.4	16.5

Health status	79.2	80.2	81.5	81.9

Illness	12.9	12.8	12.3	10.2

Chronic disease	16.6	17.0	18.7	16.0

Control variables

Annual personal expenditure	7192	7322	6840	7026

Married	82.6	81.9	63.5	61.5

Other married status	8.5	8.3	10.8	11.6

Commercial health insurance	5.1	4.3	4.7	4.0

Household population	3.5	3.6	3.5	3.5

Distance to the nearest health institution	10.0	8.8	9.8	9.5


Classification	 	BMI (kg/m2)

Underweight (A)	Thinness class III	< 16.00

 	Thinness class II	16.00-16.99

 	Thinness class I	17.00-18.49

Normal (B)	Eutrophia	18.50-22.99

 	 	23.00-24.99

Overweight (C)	Pre-obesity	25.00-27.49

 	 	27.50-29.99

Obesity (D)	Obesity class I	30.00-32.49

 	 	32.50-34.99

 	Obesity class II	35.00-37.49

 	 	38.00-39.99

 	Obesity class III	≥ 40.00

Classification		BMI (kg/m2)

	Obesity class II	35.00-37.49

		38.00-39.99

	Obesity class III	≥ 40.00


	Principal Components

	PC1	PC2	PC3	PC4	PC5

BMI	0,80	0,20	−0,23	0,20	−0,28

Waist circumference	0,75	0,23	−0,39	0,18	−0,15

Systolic blood pressure	0,72	−0,21	0,03	0,39	0,38

Diastolic blood pressure	0,56	−0,38	0,03	0,35	0,54

Fasting plasma glucose	0,19	−0,15	−0,31	−0,59	0,36


CATEGORY	ISSUES	EXAMPLES

Human resources	Teachers	“Some people hate school because teachers are terrible, they are not teaching and do not know how to teach.”

Managers	“Managers do not care about our quality of life.”

Moral abuse	Residents and teachers	“There are arrogant teachers.”

Demandings	Personal, familiar, institutional, and social	“The least I can do is to push myself as much as I can do.”

“Pressure in the medical program is big.”

Eating habits	Inadequate eating habits	“I learned from a resident to put lots of sugar in my coffee to curb the hunger.”

Financial resources	Financial dependence	“You cannot work during the program; I feel bad for being dependent on my parents.”

Lack of care with own health	Students adopt unhealthy life	“You see many medical students getting sick, being down, neglecting one's own body, unable to reflect on these things.”

Sleep	Sleep privacy	“I want, I need to sleep. I cannot do more shifts and study.”

Time	Demands of the program	“I think excessive workload decreases quality of life. You have class every day and then you have to study but you also have many other things in your life.”

 	 	“In the program there’s a lack of quality of life. Lack of time to lose, to think about life, plans, dreams.”

Demandings	Personal, familiar, institutional, and social	“Pressure in the medical program is big.”

Eating habits	Inadequate eating habits	“I learned from a resident to put lots of sugar in my coffee to curb the hunger.”

Financial resources	Financial dependence	“You cannot work during the program; I feel bad for being dependent on my parents.”

Lack of care with own health	Students adopt unhealthy life	“You see many medical students getting sick, being down, neglecting one's own body, unable to reflect on these things.”

Sleep	Sleep privacy	“I want, I need to sleep. I cannot do more shifts and study.”

Time	Demands of the program	“I think excessive workload decreases quality of life. You have class every day and then you have to study but you also have many other things in your life.”

		“In the program there’s a lack of quality of life. Lack of time to lose, to think about life, plans, dreams.”


De Qi Characteristics	Acupuncture		Mock laser

C 1	C2	De Qi Characteristics	C 1	C 2

Dull pain	.857		Heaviness	.914

Sharp pain	.823		Aching	.887

Throbbing	.770		Deep pressure	.857

Cold	.761		Soreness	.836

Tingling	.728		Fullness/ Distension	.766

Warmth	.697		Warmth	.727

Aching	.575		Tingling	.668

Fullness/ Distension		−.912	Sharp pain	.614

Soreness		−.899	Numbness	.511

Deep pressure		−.847	Throbbing		.889

Heaviness		−.781	Cold		.847

Numbness		−.664	Dull pain		.598

De Qi Characteristics	C 1	C2	De Qi Characteristics	C 1	C 2

Dull pain	.857		Heaviness	.914

Sharp pain	.823		Aching	.887

Throbbing	.770		Deep pressure	.857

Cold	.761		Soreness	.836

Tingling	.728		Fullness/ Distension	.766

Warmth	.697		Warmth	.727

Aching	.575		Tingling	.668

Fullness/ Distension		−.912	Sharp pain	.614

Soreness		−.899	Numbness	.511

Deep pressure		−.847	Throbbing		.889

Heaviness		−.781	Cold		.847

Numbness		−.664	Dull pain		.598


	Body weight	BMI	WC	VFA	SFA	FPG	2-h PG	HOMA-IR	OGIS	HOMA-β	II

Essential AAs

 Histidine	—	—	—	—	—	—	—	—	—	—	—

 Isoleucine	0.413	0.305	0.345	0.332	—	—	—	—	—	—	—

 Leucine	0.488	0.300	0.361	0.413	—	—	—	—	—	—	—

 Lysine	0.307	—	0.290	—	—	0.236	—	—	−0.257	—	—

 Methionine	—	—	—	—	—	—	—	—	—	—	—

 Phenylalanine	0.276	—	—	—	—	—	—	—	—	—	—

 Threonine	—	—	—	—	—	—	—	—	—	—	—

 Tryptophan	—	—	—	0.289	—	—	—	—	—	—	—

 Valine	0.539	0.387	0.482	0.397	—	0.254	—	0.219	−0.297	—	—

Nonessential AAs										—

 Alanine	—	—	—	—	—	—	—	—	—	—	—

 Arginine	—	—	—	—	—	—	—	—	—	—	—

 Asparagine	—	—	—	—	—	—	—	—	—	—	—

 α-ABA	—	—	—	—	—	—	—	—	—	—	—

 Citrulline	—	—	−0.242	—	−0.395	—	—	−0.291	—	−0.375	—

 Cystine	0.276	—	0.285	—	—	0.236	—	—	—	—	—

 Glutamate	0.548	0.443	0.528	0.568	—	0.439	0.302	0.292	−0.458	—	—

 Glutamine	−0.241	−0.289	−0.326	−0.272	−0.396	—	−0.220	−0.398	—	−0.311	—

 Glycine	−0.333	−0.418	−0.426	−0.426	−0.294	—	−0.247	−0.317	0.303	−0.231	—

 Ornithine	—	—	—	—	—	—	—	—	—	—	—

 Proline	—	—	—	—	—	—	—	—	—	—	—

 Serine	−0.368	−0.273	−0.351	−0.379	—	—	—	—	0.258	—	—

 Taurine	—	—	—	—	—	−0.240	—	—	—	—	—

 Tyrosine	0.335	—	0.314	0.252	—	0.269	—	—	−0.327	—	—

Essential AAs

Histidine

Isoleucine

Leucine

Lysine

Methionine

Phenylalanine

Threonine

Tryptophan

Valine

Nonessential AAs

Alanine

Arginine

Asparagine

α-ABA

Citrulline

Cystine

Glutamate

Glutamine

Glycine

Ornithine

Proline

Serine

Taurine

Tyrosine


	LD blocka	SNP	Genotype	n	Hazard ratio	95% confidence interval	P for trend

IRS		rs1	GG	99


Characteristics	2005-2006	2006-2007	2007-2008	2008-2009

No. of programs enrolledin ILC	23	63	80	87

No. of ILC registrants	5596	6920	6136	10,327

Total no. of participantscompleting CKD module	560	1322	1435	1686

Population included in currentstudy*

No. of programs	23	61	76	87

No. of participants (%)	509	1233	1351	1609

PGY-1	161 (32)	466 (36)	503 (37)	698 (43)

PGY-2	176 (34)	399 (32)	483 (36)	482 (30)

PGY-3	172 (34)	388 (32)	365 (27)	429 (27)

Programs affiliated with renalfellowship, n (%)	11 (48)	27 (43)	33 (43)	38 (44)

Programs by regional ESKDrate, n (%)

Located in region withhighest ESKD rate	6 (26)	26 (43)	26 (34)	27 (31)

Located in region withlowest ESKD rate	1 (4)	6 (10)	4 (5)	9 (10)

Mean pre-test score,% (SD)	45.1 (18.2)	49.3 (19.3)	57.0 (20.2)	55.2 (19.8)

Characteristics	2005-2006	2006-2007

No. of programs enrolledin ILC	23	63

No. of ILC registrants	5596	6920

Total no. of participantscompleting CKD module	560	1322

Population included in currentstudy*

No. of programs	23	61

No. of participants (%)	509	1233

PGY-1	161 (32)	466 (36)

PGY-2	176 (34)	399 (32)

PGY-3	172 (34)	388 (32)

Programs affiliated with renalfellowship, n (%)	11 (48)	27 (43)

Programs by regional ESKDrate, n (%)

Located in region withhighest ESKD rate	6 (26)	26 (43)

Located in region withlowest ESKD rate	1 (4)	6 (10)

Mean pre-test score,% (SD)	45.1 (18.2)	49.3 (19.3)


Gene (species)	Sequence 5′→3′

CCL-2 (Homo sapiens) (NM 002982.3)	Fw: TCA GCC AGA TGC AAT CAA TG

Rev: ACA CTT GCT GCT GGT GAT TCT

IL-1β (Homo sapiens) (NM 000576.2)	Fw: AGC CAA TCT TCA TTG CTC AAG T

Rev: AGT CAT CCT CAT TGC CAC TGT

IL-6 (Homo sapiens) (NM 000600.3)	Fw: CAG CCC TGA GAA AGG AGA CAT

Rev: AGC CAT CTT TGG AAG GTT CA

IFN-γ (Homo sapiens) (NM 000619.2)	Fw: TGG AAA GAG GAG AGT GAC AGA A

Rev: TTG GAT GCT CTG GTC ATC TTT A

TNF-α (Homo sapiens) (NM 000594.3)	Fw: CTC TCT CCC CTG GAA AGG AC

Rev: ATC ACT CCA AAG TGC AGC AG

IL- 10 (Homo sapiens) (NM 000572.2)	Fw: TGTCATCGATTTCTTCCCTGT

Rev: TGC CTT TCT CTT GGA GCT TAT T

RPL-27(Homo sapiens) (NM 000988.3)	Fw: CCG AAA TGG GCA AGT TCA T

Rev: CCA TCA TCA ATG TTC TTC ACG A

IL-8 (Homo sapiens) (NM 000584.3)	Fw: AGC TCT GTG TGA AGG TGA T

Rev: TTT GGG GTG GAA AGG TTT G

ZAG (Homo sapiens) (NM 001185.3)	Fw: CCA GGA GAA CCA AGA TGG TC

Rev: CTG CTT CCA ATC CTC CAT TC

PIF (Homo sapiens) (NM 005268627.1)	Fw: AGG AAG CAG AGA TCC AGC CT

Rev: GGC TCC TTT ACC CAC GCT TT

HPRT1(Homo sapiens) (NM 000194.2)	Fw: TGG CGT CGT GAT TAG TGA TG

Rev: CTT GAG CAC ACA GAG GGC TA

Gene (species)

CCL-2 (Homo sapiens) (NM 002982.3)

IL-1β (Homo sapiens) (NM 000576.2)

IL-6 (Homo sapiens) (NM 000600.3)

IFN-γ (Homo sapiens) (NM 000619.2)

TNF-α (Homo sapiens) (NM 000594.3)

IL- 10 (Homo sapiens) (NM 000572.2)

RPL-27(Homo sapiens) (NM 000988.3)

IL-8 (Homo sapiens) (NM 000584.3)

ZAG (Homo sapiens) (NM 001185.3)

PIF (Homo sapiens) (NM 005268627.1)

HPRT1(Homo sapiens) (NM 000194.2)

Sequence 5′→3′

Fw: TCA GCC AGA TGC AAT CAA TG

Rev: ACA CTT GCT GCT GGT GAT TCT

Fw: AGC CAA TCT TCA TTG CTC AAG T

Rev: AGT CAT CCT CAT TGC CAC TGT

Fw: CAG CCC TGA GAA AGG AGA CAT

Rev: AGC CAT CTT TGG AAG GTT CA

Fw: TGG AAA GAG GAG AGT GAC AGA A

Rev: TTG GAT GCT CTG GTC ATC TTT A

Fw: CTC TCT CCC CTG GAA AGG AC

Rev: ATC ACT CCA AAG TGC AGC AG

Fw: TGTCATCGATTTCTTCCCTGT

Rev: TGC CTT TCT CTT GGA GCT TAT T

Fw: CCG AAA TGG GCA AGT TCA T

Rev: CCA TCA TCA ATG TTC TTC ACG A

Fw: AGC TCT GTG TGA AGG TGA T

Rev: TTT GGG GTG GAA AGG TTT G

Fw: CCA GGA GAA CCA AGA TGG TC

Rev: CTG CTT CCA ATC CTC CAT TC

Fw: AGG AAG CAG AGA TCC AGC CT

Rev: GGC TCC TTT ACC CAC GCT TT

Fw: TGG CGT CGT GAT TAG TGA TG

Rev: CTT GAG CAC ACA GAG GGC TA


Tool	URL	References

BLAST	http://blast.ncbi.nlm.nih.gov/Blast.cgi	(18)

MAFFT MSA	http://www.ebi.ac.uk/Tools/msa/mafft/	(19)

NetMHCpan	http://www.cbs.dtu.dk/services/NetMHCpan/	(20)

NetMHCIIpan	http://www.cbs.dtu.dk/services/NetMHCIIpan/	(21)

Search tool for HPV antigens	http://cvc.dfci.harvard.edu/hpv/HTML/search.php

Search tool for T cell epitope/HLA ligand	http://cvc.dfci.harvard.edu/hpv/HTML/searchT.php

Blast HPVdb	http://cvc.dfci.harvard.edu/hpv/HTML/blast.php

MSA of HPV sequences	http://cvc.dfci.harvard.edu/hpv/HTML/alignment.php

Sequence variability analysis tool	http://cvc.dfci.harvard.edu/hpv/HTML/varability.php	(14)

T cell epitope/HLA ligand visualization tool	http://cvc.dfci.harvard.edu/hpv/HTML/viewEpitope.php

Classification of the viruses based on cancer risk	http://cvc.dfci.harvard.edu/hpv/HTML/classification.php

HLA binding prediction tool	Embedded in each antigen entry table

T cell epitope/HLA ligand conservation analysis tool	Embedded in each experimentally validated T cell epitope/HLA entry table; also embedded in each HLA binding prediction result page.

Tool	URL	References

BLAST	http://blast.ncbi.nlm.nih.gov/Blast.cgi	(18)

MAFFT MSA	http://www.ebi.ac.uk/Tools/msa/mafft/	(19)

NetMHCpan	http://www.cbs.dtu.dk/services/NetMHCpan/	(20)

NetMHCIIpan	http://www.cbs.dtu.dk/services/NetMHCIIpan/	(21)

Search tool for HPV antigens	http://cvc.dfci.harvard.edu/hpv/HTML/search.php

Search tool for T cell epitope/HLA ligand	http://cvc.dfci.harvard.edu/hpv/HTML/searchT.php

Blast HPVdb	http://cvc.dfci.harvard.edu/hpv/HTML/blast.php

MSA of HPV sequences	http://cvc.dfci.harvard.edu/hpv/HTML/alignment.php

Sequence variability analysis tool	http://cvc.dfci.harvard.edu/hpv/HTML/varability.php	(14)

T cell epitope/HLA ligand visualization tool	http://cvc.dfci.harvard.edu/hpv/HTML/viewEpitope.php

Classification of the viruses based on cancer risk	http://cvc.dfci.harvard.edu/hpv/HTML/classification.php

HLA binding prediction t	Emb

Tool	URL	References

ool	edded in each antigen entry table

T cell epitope/HLA ligand conservation analysis tool	Embedded in each experimentally validated T cell epitope/HLA entry table; also embedded in each HLA binding prediction result page.


Gene	Low n-3 LC-PUFA HL/LL	High n-3 LC-PUFA HH/LH

 	Microarray	RT-qPCR	Microarray	RT-qPCR

LC-PUFA biosynthesis

Δ5fad	 	−1.03	 	1.35

Δ6fad	 	1.04	 	−1.32

elovl2	−1.28 to −1.41	−1.51	−1.82 to −1.97	−1.62

Cholesterol biosynthesis

ipi	 	−3.95	 	1.31

mev	 	−1.40	 	1.14

7dchr	 	−1.01	 	1.09

srebp2	 	−2.09	 	1.29

Lipid transport and lipoprotein metabolism

lrp1	 	−1.82	 	−1.08

apoA4a	 	−1.37	 	−0.95

apoA4b	 	−2.43	 	−1.80

lpl	 	−1.18	 	−1.05

Immune response

cfh	−1.33 to −1.56	−1.24	−1.56 to −1.69	−1.31

trim25	−5.64	−2.09	−4.34	−2.33

lect2	3.16	1.23	4.86	4.84

Gene	Low n-3 LC-PUFA HL/LL	High n-3 LC-PUFA HH/LH

	Microarray	RT-qPCR	Microarray	RT-qPCR

LC-PUFA biosynthesis

Δ5fad		−1.03		1.35

Δ6fad		1.04		−1.32

el		−	−1.8	−1.

Gene	Low n-3 LC-PUFA HL/LL	High n-3 LC-PUFA HH/LH

	Microarray	RT-qPCR	Microarray	RT-qPCR

ovl2	−1.28 to −1.41	1.51	2 to −1.97	62

Cholesterol biosynthesis

ipi		−3.95		1.31

mev		−1.40		1.14

7dchr		−1.01		1.09

srebp2		−2.09		1.29

Lipid transport and lipoprotein metabolism

lrp1		−1.82		−1.08

apoA4a		−1.37		−0.95

apoA4b		−2.43		−1.80

lpl		−1.18		−1.05

Immune response

cfh	−1.33 to −1.56	−1.24	−1.56 to −1.69	−1.31

trim25	−5.64	−2.09	−4.34	−2.33

lect2	3.16	1.23	4.86	4.84


Characteristics	Healthcare worker (%) n = 114	Other (%)an = 41

Country

Mozambique	35 (31%)	36 (88%)

India	20 (18%)	0 (0%)

Nigeria	19 (17%)	5 (12%)

South Africa	40 (35%)	0 (0%)

Facility level

Community	40 (35%)	NA

Primary health centre	34 (30%)	NA

Hospital	40 (35%)	NA

Age (years)

15–20	1 (1%)	6 (15%)

21–30	36 (32%)	16 (39%)

31–40	37 (32%)	15 (37%)


Position 1	NY-3356 Genome	IC Plasmids	Amino Acid Change	Location

1285	T	C	Silent	E

3840	T	C	Silent	NS2A

70292	G	A	Silent	NS4B

7826	T	C	V➔A	NS5

8067	G	A	Silent	NS5

9123	C	T	Silent	NS5

10613	C	T	Silent	3’ UTR

10783	C	T	Silent	3’ UTR


Bioprosthesis type	Manufacturer	Valve diameters (mm)

Trifecta	St. Jude Medical, Minneapolis, USA	19 to 29

Mitroflow	Sorin Group, Saluggia, Italy	19 to 29

Carpentier-Edwards Magna Ease	Edwards Lifesciences, Irvine, USA	19 to 29


Process Modes	Position (cm)	Velocity (cm/s)	Attitude (°)

North	East	Down	North	East	Down	Roll	Pitch	Heading

IC-PPP	6.6	8.9	6.6	6.7	7.2	8.3	-	-	-

IC-PPP/INS	3.2	4.8	5.5	1.0	1.1	0.8	0.021	0.026	0.092

LC-PPP/INS	4.2	6.5	6.1	1.2	1.1	0.9	0.022	0.027	0.095


Underlying medical condition	All	<5 years	5 - 59 years	60+ years	Pregnant or postpartum

N = 183	n = 29	n = 134	n = 20	n = 27

Cases	%	Cases	%	Cases	%	Cases	%	Cases	%

Obesity	27	15 %	0	0 %	23	17 %	4	21 %	2	7 %

Diabetes Mellitus	23	13 %	0	0 %	16	12 %	7	37 %	2	7 %

Asthma	20	11 %	2	7 %	15	11 %	3	16 %	5	18 %

Other chronic metabolic disease	15	8 %	1	3 %	9	7 %	5	26 %	0	0 %

Immunosuppression	15	8 %	2	7 %	10	7 %	3	16 %	1	4 %

Chronic lung disease	10	5 %	0	0 %	8	6 %	2	11 %	2	7 %

Chronic seizures	11	6 %	3	10 %	8	6 %	0	0 %	0	0 %

Chronic cardiac disease	7	4 %	1	3 %	5	4 %	1	5 %	3	11 %

Cerebral palsy	7	4 %	1	3 %	6	4 %	0	0 %	0	0 %

At least one chronic condition	112	61 %	11	38 %	82	61 %	19	100 %	14	50 %


	All gabor	Papillary gabor	Reticular gabor	All FFT	Papillary FFT	Reticular FFT

95% CI	−0.999 to −0.209	−0.999 to 0.284	−0.999 to −0.276	−0.370 to 0.999	−0.574 to 0.997	−0.171 to 0.999


Follow-up	Targeted group	Nontargeted group	Medium alone


 	Korea	Japan

Expenditures on health by type of funding (%)

GG/SS/POP/PI	11/46/37/6	9/73/15/2

Share of hospital inpatient expenditures for MSD (%)	9	6

Health care system

Out-of-pocket healthcare expenditures as a share of total household consumption (%)	4.6	2.2

Sickness leave	No	66.7% of average daily basic wage up to 18 months

Share of WMSD in workers’ compensation (%)

WMSD/total compensated diseases	71.5	66.6

WMSD/total compensated injury and diseases	5.8	4.3

Expenditures on health by type of funding (%)

GG/SS/POP/PI

Share of hospital inpatient expenditures for MSD (%)

Health care system

Out-of-pocket healthcare expenditures as a share of total household consumption (%)

Sickness leave

Share of WMSD in workers’ compensation (%)

WMSD/total compensated diseases

WMSD/total compensated injury and diseases


Parameter	Cirrhosis	Controls

Bilirubin (total, mg/dL)	1.44 ± 0.95	0.89 ± 0.24

Albumin (gm/dL)	4.0 ± 0.5	3.7 ± 0.9

PT (secs)	14.4 ± 1.8	11.4 ± 0.8

Ascites	2/26	0/13

Enceplalopathy	0/26	0/13


Symbol	Chr	UCSC annotated features	CpG island	Δ β-value	Bootstrap 95% CI

OBFC2B	12	Promoter associated	Shore	0.386	(0.227, 0.551)

GPR75; LOC100302652	2	5′UTR; 1st Exon; Enhancer	Island	0.349	(0.184, 0.515)

AIRE	21	Within 100 bp of TSS	Island	0.267	(0.094, 0.444)

MIMT1; PEG3;ZIM2	19	Within 500 bp of TSS; 5′UTR; 5′UTR	Island	0.207	(0.088, 0.332)

CIRBP; C19orf24	19	Body; Within 1000 bp of TSS	Island	0.176	(0.097, 0.256)

SMG6; SRR	17	Within 500 bp of TSS; 5′UTR	Shore	0.125	(0.039, 0.214)

GPR12	13	5′UTR	Island	-0.095	(-0.161, -0.030)

Symbol	Chr	UCSC annotated features	CpG island	Δ β-value	Bootstrap 95% CI

OBFC2B	12	Promoter associated	Shore	0.386	(0.227, 0.551)

GPR75; LOC100302652	2	5′UTR; 1st Exon; Enhancer	Island	0.349	(0.184, 0.515)

A	21	Within 100 b	Is	0	(0.094, 0.44

Symbol	Chr	UCSC annotated features	CpG island	Δ β-value	Bootstrap 95% CI

IRE		p of TSS	land	.267	4)

MIMT1; PEG3;ZIM2	19	Within 500 bp of TSS; 5′UTR; 5′UTR	Island	0.207	(0.088, 0.332)

CIRBP; C19orf24	19	Body; Within 1000 bp of TSS	Island	0.176	(0.097, 0.256)

SMG6; SRR	17	Within 500 bp of TSS; 5′UTR	Shore	0.125	(0.039, 0.214)

GPR12	13	5′UTR	Island	-0.095	(-0.161, -0.030)


Rab	Determination on WPBs	Method	siRNA effect on VWF release	Comment	Reference

Rab27a	Endogenous expression and overexpression	Western blot, RT-PCR, and IF	Increase or decrease	–	26,34,47,50

Rab27b	Overexpression	RT-PCR	Decrease	Level of expression very low	47

Rab3A	Overexpression	RT-PCR	Decrease	–	47

Rab3B	Endogenous expression and overexpression	Western blot, RT-PCR, and IF	No effect	–	47,50

Rab3D	Endogenous expression and overexpression	Western blot, RT-PCR, and IF	Decrease or no effect	Endogenous Rab3D weakly detectable in 5% of cells	47,50,52

Rab15	Overexpression	RT-PCR	Decrease	–	47

Rab33a	Overexpression	RT-PCR	No effect	–	47

Rab37	Overexpression	RT-PCR	No effect	Low expression (cycle time 39.74)	47

Rab

Rab27a

Rab27b

Rab3A

Rab3B

Rab3D

Rab15

Rab33a

Rab37

Determination on WPBs	Method	siRNA effect on VWF release	Comment	Reference

Endogenous expression and overexpression	Western blot, RT-PCR, and IF	Increase or decrease	–	26,34,47,50

Overexpression	RT-PCR	Decrease	Level of expression very low	47

Overexpression	RT-PCR	Decrease	–	47

Endogenous expression and overexpression	Western blot, RT-PCR, and IF	No effect	–	47,50

Endogenous expression and overexpression	Western blot, RT-PCR, and IF	Decrease or no effect	Endogenous Rab3D weakly detectable in 5% of cells	47,50,52

Overexpression	RT-PCR	Decrease	–	47

Overexpression	RT-PCR	No effect	–	47

Overexpression	RT-PCR	No effect	Low expression (cycle time 39.74)	47


	Region	Number	Mean ± SD	Min–max	Median	Lower quartile	Upper quartile

NP (ng g−1 d	Bornholm Deep	13	14.04 ± 21.50	ND–71.92	3.21	1.64	22.88

S-W Gotland Deep	13	68.67 ± 95.50	0.43–239.88	8.09	1.51	170.08

Gdansk D		27.39 ± 30.6	0.7	5	2.07	57.3


	Odds ratio	95 % C.I. for odds ratio	P value

		Lower	Upper

External environment

Area of residence

Rural	1

Urban	1.364	1.081	1.721	0.009

Education

Non	1

Primary	1.666	1.297	2.141	0.001

Secondary +	1.929	1.380	2.697	0.001

Adult education	1.191	.688	2.063	0.533

Wealth index

Wealth index(score)	2.293	1.988	2.644	0.001

Parity

Parity >2	1

Parity 1-2	2.222	1.786	2.765	0.001

Enabling factors

Ante natal care

No	1

Yes	3.342	2.306	4.844	0.001

Need factors

Complications during pregnancy

No/Non-serious complication	1

Serious complication	1.606	1.319	1.957	0.001

	Odds ratio

External environment

Area of residence

Rural	1

Urban	1.364

Education

Non	1

Primary	1.666

Secondary +	1.929

Adult education	1.191

Wealth index

Wealth index(score)	2.293

Parity

Parity >2	1

Parity 1-2	2.222

Enabling factors

Ante natal care

No	1

Yes	3.342

Need factors

Complications during pregnancy

No/Non-serious complication	1

Serious complication	1.606


Gene	Sequence

GK	forward 5′-TTGAGACCCGTTTCGTGTCA – 3′

	reverse 5′-AGGGTCGAAGCCCCAGAGT -3′

L-PK	forward 5′-TGATGATTGGACGCTGCAA – 3′

	reverse 5′-GAGTTGGTCGAGCCTTAGTGATC – 3′

HK2	forward 5′-AACCGAACAAGCTGGTGTAC-3′

	reverse 5′-TGCACACATCTATAGGTGGC-3′

ACC	forward 5′-CAACGCCTTCACACCACCTT -3′

	reverse 5′-AGCCCATTACTTCATCAAAGATCCT -3′

FAS	forward 5′-TGCTCCCAGCTGCAG -3′

	reverse 5′-GCCCGGTAGCTCTGGGTGTA -3′

ACOX1	forward 5′-AAGAAATCCCCACTGAACAAAACA -3′

	reverse 5′-CCCAGGGAAACTTCAAAGCTT -3′

CPT1a	forward 5′-ATATCAAGGACAGCAGGCACAT -3′

	reverse 5′-CTCAGCAGCCTCCCATGCT -3′

CPT1 b	forward 5′-CAGCCATGCCACCAAGATC -3′

	reverse 5′-CTTGGGCAGTGATGTTTGGA -3′

CD36	forward 5′-CAGCCTCCTTTCCACCTTTTG-3′

	reverse 5′-AAGGCGTTGGCTGGAAGAA-3′

PGC1α	forward 5′-ATACCGCAAAGAGCACGAGAAG-3′

	reverse 5′-CTCAAGAGCAGCGAAAGCGTCACAG-3′

PPARα	forward 5′-GGGATGAAGAGGGCTGAGC-3′

	reverse 5′-TGATTAACATTGGGCCGGTT-3′

BCAT2	forward 5′-GGCGGACCCTTCATTCGT-3′

	reverse 5′-TTCCCCCCCAACTTGCA-3′

BCKDHα	forward 5′-CCAGGGTTGGTGGGATGAG-3′

	reverse 5′-GGCTTCCATGACCTTCTTTCG-3′

UBE2B	forward 5′-AACGCAGTTATATTTGGACCAGAAG-3′

	reverse 5′-ACGGTTGGTGGTTTATTTGGAT-3′

CAD	forward 5′-CGCAGTGTTTCACAGTCGTCTT-3′

	reverse 5′-TGGACTTGTCACTGTTGTACTTATGG-3′

CCK	forward 5′-CAGGTCCGCAAAGCTCCTT3′

	reverse 5′-TCCAGGCTCTGCAGGTTCTT-3′

PYY	forward 5′-CGGCAGCGGTATGGAAAA-3′

	reverse 5′-TGTGAAGAGCAGTTTGGAGAACA-3′

GLP-1	forward 5′-CTCCCGCCGTGCTCAA-3′

	reverse 5′-TTGTTCCGGTTCCTCTTGGT-3′

GIP	forward 5′-CTGCTGGTGCTCCTGTTCCT-3′

	reverse 5′-CATGGGATCGGAACTCAACCT-3′


Discipline	Number

Medical	11,323

Nurses and midwives	40,926

Dentists	3,176

Pharmacists	1,100

Other HCW	16,640

Administrative staff	34,533

Total	107,698

Discipline	Number

Administrative staff	34,533

Total	107,698


Key challenges	Solutions	Future implications

1) Identification of centres willing/able to participate in the study

• Identifying centres with interest/capacity to participate in research and the correct people to discuss participation with proved difficult via conventional means (unsolicited mail/email).• Limitations in dedicating time or resources to external research projects due to clinical workloads and lack of designated support staff were common reasons for non-participation cited by centres. Levels of remuneration provided to centres for participation in the study were considered insufficient by some centres.• Availability of NHS staff participating in research having completed Good Clinical Practice (GCP) training.	• The ZQOL study was accepted into the National Institute for Health Research Clinical Research Network (NIHR CRN) portfolio. NIHR were able to offer wide range of support services including:o Access to existing networks of centres with interests in participating in research.o Provision of support to centres interesting in participating in research.o Exploring centre eligibility for additional remuneration for participation in NIHR CRN-approved studies.o Delivering GCP training to centres interesting in participating in studies.	• Experiences indicate the need for greater links between commissioners of research and primary/secondary care centres.• A refocusing of targets for primary care centres, to provide staff with opportunities and incentives for partaking in research is needed.• Current R&D approval process makes no concessions for non-interventional research. R&D requirements should be proportionate to the risks associated with patient participation in such studies.

2) Obtaining Ethics and Research & Development (R&D) Management Approval

• Information and documentation required to support R&D applications was a barrier to participation for a number of centres.• Significant variation in timelines for R&D approval at a local and regional level (i.e. England, Scotland, Wales & Northern Ireland) led to significant delays in the study.• R&D approval process requires that extensive tri-partite agreements between the study sponsor, co-ordinating CRO and R&D department be agreed and signed. However, there is no standard template available for such agreements.	• ZQOL study organisers implemented a number of practical solutions including:o Minimising the number of R&D approvals by seeking participation of clusters of centres in the same NHS trust.o Implemented a staged study roll-out such that R&D applications for key centres were prioritised and R&D applications could occur in parallel to patient recruitment.• NIHR CRN can also provide assistance:o As a NIHR-CRN portfolio adopted study, more likely to be considered for priority review by R&D depts.o NIHR CRN local research network teams are able to offer support and guidance to co-ordinating CROs throughout England.	• Current R&D approval process makes no concessions for non-interventional research. R&D requirements should be proportionate to the risks associated with patient participation in such studies.• A move to standardise R&D approval process across NHS trusts in England would reduce burden (and barriers) to research for study organisers and NHS staff interested in participating in research.

3) Recruitment of Study Participants

• Recruitment of HZ patients in primary care was slower than envisaged, a likely result of practical and organisational factors:o As an acute condition, HZ patients had to be recruited on initial presentation to physicians and did not allow searches of eligible participants via patient medical records.o At the time of the study there will only limited opportunities for notifications and reminders to be incorporated into electronic-record systems on presentation of incident cases.• Lack of unique identifiers or codes in electronic-record systems made it difficult to identify PHN patients for participation in the ZQOL study.	• To ensure that study recruitment quotas were met, additional centres were recruited for participation in the study and study timelines were extended.• NIHR CRN local research networks and the co-ordinating CRO were in regular contact with centre staff so to ensure to provide support where needed.	• Standardisation of medical record keeping and greater integration of record and monitoring systems would be to the benefit of facilitating real-world research.• Centres having systems in place to confirm the feasibility of recruitment numbers and having opportunity to work alongside study organisers could facilitate the development of study inclusion/exclusion criteria that are less restrictive to recruitment in real-world practice.


Case	Case summary	Examination type	Performing department	Allegation

1	Middle-aged female presented with calf pain. Ultrasound study reported to be negative. Patient had fatal pulmonary embolism. (2012 WL 1100657 [Ohio App. 7 Dist])	DVT	Radiology	Failure to perform complete examination

2	Teen-aged female presented with calf pain, palpitations and pre-syncope. EKG and chest x-ray normal. Patient died of massive pulmonary embolism. (2012 WL 1605709 (La.App. 5 Cir.), 11–1006 [La.App. 5 Cir. 5/8/12])	DVT	Not performed	Failure to perform

3	Teen-aged boy presented after motor vehicle collision. No abdominal imaging was performed. Patient was discharged and died that night at home with liver laceration and hemoperitoneum. (721 S.E.2d 238)	FAST	Not performed	Failure to perform

4	Adult female presented with abdominal pain. Right upper quadrant ultrasound scheduled next day. Positive for cholecystitis. Alleged delay in diagnosis prolonging hospitalization and causing complications. (2009 WL 2473514)	RUQ	Radiology	Failure to perform in a timely manner

5	Adolescent male 8 days status post knee arthroscopy presented with chest pain. Diagnosed with pleurisy and discharged. Patient subsequently died of bilateral pulmonary emboli. (2012 WL 5910796)	DVT	Not performed	Failure to perform


Group	n	Before Treatment	After Treatment	Comparison

F	P


	ARDS patients	Age- and sex-matched reference values	P value

	Mean (SD)	Mean (SD)

EQ5D index at 6 months

Patients under 65	0.55 (0.37)	0.85 (0.06)	<0.001

Patients 65 and above	0.62 (0.37)	0.77 (0.02)	0.003

EQ5D at 12 months

Patients under 65	0.58 (0.35)	0.85 (0.06)	<0.001

Patients 65 and above	0.58 (0.38)	0.77 (0.02)	<0.001


	Total sample

	N

Sex

Male	48 910

Female	51 090

Age

20–39	27 706

40–59	37 106

60–79	28 868

80-	6 320

Marital statusa

Single	31 140

Married/living together	63 807

Educational levela

Low	24 770

Medium	40 659

High	25 752

Income levela

Low	22 440

Medium	48 126

High	24 382

Employment statusa

Workning	59 961

Pensioners	23 193

Out of workforce	11 911

Ethnic groupsa

Danish	86 248

Immigrants	8 038

Descendants of Immigrants	661

GP contactsa

Average contacts to GP in 2011	8.1


Variable	25th percentile	50th percentile	75th percentile

GC	0.298	0.318	0.353

RHI	0.218	0.233	0.260

80/20 ratio	5.550	6.570	8.155

All-cause mortality rate (/100,000)	378.5	416.3	441.7

Community population	165,980.8	280,277.0	363,011.0

Percent of over 65 years in community population (%)	8.9	10.8	13.8

Ratio of social welfare expenditure (%)	23.9	30.9	44.6

Number of physicians (/1,000)	1.6	2.0	2.8

Smoking rate (%)	22.0	24.0	25.0

Drinking rate (%)	56.0	59.0	61.0


	2016	2017	2018	2019

Q2	Q3	Q4	Q1	Q2	Q3	Q4	Q1	Q2	Q3	Q4	Q1	Q2	Q3	Q4

Protocol development	X

Training of research coordinators and physicians	X		X	X				X

Training of nurses for motivational counseling (yearly refresher training)		X			X				X

Obtaining informed consent, recruitment, and baseline interview				X	X	X	X

Auditing and site visit monitoring (every 2 weeks)				X	X	X	X	X	X	X	X	X	X	X	X

Trial supervision			X				X				X				X

Monthly Trial Management Committee meeting				X	X	X	X	X	X	X	X	X	X	X	X

Telephone follow-up by nurses (monthly until 3 months and then every 3 months)				X	X	X	X	X	X	X	X	X	X	X	X

Follow-up by clinical research coordinators (every 4 months by telephone; annually on site)					X	X	X	X	X	X	X	X	X	X	X

Data Safety and Monitoring Board meeting (every 6 months)		X			X		X		X		X		X		X

Trial Steering Committee Meeting (every 6 months)		X		X		X		X		X		X		X

Quality assessment			X			X			X			X			X

Progress or interim report						X

Data analysis														X	X

Manuscript writing														X	X

Final report														X	X

Protocol development

Training of research coordinators and physicians

Training of nurses for motivational counseling (yearly refresher training)

Obtaining informed consent, recruitment, and baseline interview

Auditing and site visit monitoring (every 2 weeks)

Trial supervision

Monthly Trial Management Committee meeting

Telephone follow-up by nurses (monthly until 3 months and then every 3 months)

Follow-up by clinical research coordinators (every 4 months by telephone; annually on site)

Data Safety and Monitoring Board meeting (every 6 months)

Trial Steering Committee Meeting (every 6 months)

Quality assessment

Progress or interim report

Data analysis

Manuscript writing

Final report

2016	2017	2018	2019

Q2	Q3	Q4	Q1	Q2	Q3	Q4	Q1	Q2	Q3	Q4	Q1	Q2	Q3	Q4

X

X		X	X				X

	X			X				X

			X	X	X	X

			X	X	X	X	X	X	X	X	X	X	X	X

		X				X				X				X

			X	X	X	X	X	X	X	X	X	X	X	X

			X	X	X	X	X	X	X	X	X	X	X	X

				X	X	X	X	X	X	X	X	X	X	X

	X			X		X		X		X		X		X

	X		X		X		X		X		X		X

		X			X			X			X			X

					X

													X	X

													X	X

													X	X


Diets	Intestine	Liver	Muscle	Brain

HD

LD				fabp7b

LND	fabp1b.1, fabp7b		fabp7a

LFD		fabp7a	fabp11a


 	Midwives	Child health nurses	Dental hygienists/dental nurses

 	Raising the topic with more than half or all pregnant women (%)	Wilcoxon Signed Rank Test	Raising the topic with more than half or all parents (%)	Wilcoxon Signed Rank Test	Raising the topic with more than half or all clients (%)	Wilcoxon Signed Rank Test

Topic	Pre	Post	p-value	Pre	Post	p-value	Pre	Post	p-value

Psychosocial health	73	86	.048	47	64	.053	-	-	-

Men’s violence against women/children	59	82	.010	11	36	.000	-	-	-

Tobacco	91	96	.581	72	89	.059	79	84	.690

Alcohol	91	96	.414	64	81	.109	0	21	.026

Drugs	91	82	.269	19	36	.004	-	-	-

Weight/BMI	76	86	.107	11	13	.169	5	26	.006

Discretionary foods	59	41	.790	23	43	.005	47	100	.001

Regular meals	59	46	.941	34	55	.035	53	100	.001

Beverage intake	-	-	-	-	-	-	63	100	.000

5 fruits and vegetables a day	67	82	.191	21	53	.000	32	100	.000

30 min daily physical activity	59	68	.129	11	36	.000	-	-	-

Parenthood/parent relationships	77	77	.623	64	83	.107	-	-	-

Tooth brushing/dental health (child)	-	-	-	55	89	.001	-	-	-

Weight/BMI (child)	-	-	-	77	81	.805	-	-	-

5 fruits and vegetables a day (child)	-	-	-	45	66	.002	-	-	-

Regular meals (child)	-	-	-	83	85	.907	-	-	-

Discretionary foods (child)	-	-	-	55	68	.026	-	-	-

Physical activity (child)	-	-	-	72	87	.068	-	-	-

Psychosocial health (child)	-	-	-	79	87	.337	-	-	-


Characteristics

Gender

Male

Female

Age (yrs)

<40

40-60

>60

AFP

≤20 (ng/mL)

>20

HBV

Negative

Positive

Histological grading

Well

Moderate

Poorly

Largest tumor size

<3cm

3-10cm

>10cm

Presence of satellite nodules

Negative

Positive

Vascular invasion

Negative

Positive

HbeAg

Negative

Positive

Tumorous number

1

>=2

Child-Pugh Classification

Child-A

Child-B

UICC stage

I+II

III+IV


	Severe (n = 12)	Mild (n = 5)

Birth Weight (g)	2500(2400–3000)a	3100 (3000–3600)	p = 0.04

Day of illness at hospital presentation	2.5 (2–3.5)	5 (5–5)	p = 0.02

Incubation period (days)	7 (7–10)	6 (5–7)	p = 0.04

	Severe (n = 12)	Mild (n = 5)

Incubation period (days)	7 (7–10)	6 (5–7)	p = 0.04


HLA alleles	Risk allele (RA)	Risk allele frequency	P-value	OR	CD groups

Indian	African	European

HLA-DQ2.2 (rs2395182)	T	0.83	0.73	0.76	1.06 × 10−5	2.72 [1.74–4.25]	Pediatric

6.26 × 10−5	1.99 [1.42–2.79]	Adult

HLA-				0.85	1.	1.89 	Pedi


Outcomes	Conventional periodn = 79 (%)	MALDI-TOF periodn = 75 (%)	P Value†

Time to pathogen identification (hours)	86.9 ± 30.4	62.5 ± 23.1	< 0.001

Time to effective therapy (hours)	27.8 ± 32.4	17.1 ± 25.7	0.031

30-day all-cause mortality	7 (8.9)	5 (6.7)	0.612

Time to microbiological clearance (days)	4.1 ± 3.0	3.4 ± 2.0	0.081

Length of ICU stay (days)	14.1 ± 26.0	11.7 ± 12.8	0.719

30-day Recurrence of same BSI	2 (2.5)	0 (0.0)	0.497


Mouse primers		Oligonucleotide sequences (5’−3’)

Aldh1a1-/-	Forward	TGAGCAAATCCTCCACAGCCCTGTTC

Reverse	CTGCTAAAGCGCATGCTCCAGACTG

Aldh1a3 flox	Forward	TCTCTGACCAGCTTTCCAACCTTCAG

Reverse	CTCAAACCAGCACCACCTCCATATTG

Sox9 flox	Forward	TCAGCAAGACTCTGGGCAAGCTCT

Reverse	CTCAAAATCTGAGCCACTCCCTC

Tyr-Cre, Pax6-α-Cre	Forward	CCTGGAAAATGCTTCTGTCCGT

Reverse	GTGTCCACATAGTCATTGGCAGAGTG

Sox9-Tg, Kdr-BAC-EGFP	Forward	AGCTGACCCTGAAGTTCATCTG

Reverse	GTCGTCCTTGAAGAAGATGGTG

Flt1-BAC-tdsRed	Forward	GCTGCAGGCGCGGAGAAGGGCTCTC

Reverse	CTTCACGTACACCTTGGAGC

IL2 (internal control)	Forward	GCCTAGAAGATGAACTTGGACCTCTG

Reverse	GTGGAAGGATTCACTTGCACAGTGAC

Human RPE primers

Sox9	Forward	CGTACCCGCACTTGCACAAC

Reverse	TCTCGCTCTCGTTCAGAAGTC

Vegfa	Forward	TGCCCGCTGCTGTCTAAT

Reverse	TCTCCGCTCTGAGCAAGG

β-actin	Forward	CCAACCGCGAGAAGATGA

Reverse	CCAGAGGCGTACAGGGATAG

Mouse primers		Oligonucleotide sequences (5’−3’)

Sox9 flox	Reverse	CTCAAAATCTGAGCCACTCCCTC

Tyr-Cre, Pax6-α-Cre	Forward	CCTGGAAAATGCTTCTGTCCGT

Reverse	GTGTCCACATAGTCATTGGCAGAGTG

Sox9-Tg, Kdr-BAC-EGFP	Forward	AGCTGACCCTGAAGTTCATCTG

Reverse	GTCGTCCTTGAAGAAGATGGTG

Flt1-BAC-tdsRed	Forward	GCTGCAGGCGCGGAGAAGGGCTCTC

Reverse	CTTCACGTACACCTTGGAGC

IL2 (internal control)	Forward	GCCTAGAAGATGAACTTGGACCTCTG

Reverse	GTGGAAGGATTCACTTGCACAGTGAC

Human RPE primers

Sox9	Forward	CGTACCCGCACTTGCACAAC

Reverse	TCTCGCTCTCGTTCAGAAGTC

Vegfa	Forward	TGCCCGCTGCTGTCTAAT

Reverse	TCTCCGCTCTGAGCAAGG

β-actin	Forward	CCAACCGCGAGAAGATGA

Reverse	CCAGAGGCGTACAGGGATAG


Survey items	Overall (n=48)	Completely achieved ILP goals and objectives

‘No’ (n=25)	‘Yes’ (n=23)

ILP helpful in structuring ACE learning objectives (Rate 1–5), no. (%)

 1-3 ratings	12 (25 %)	10 (40 %)	2 (9 %)

 4-5 ratings	36 (75 %)	15 (60 %)	21 (91 %)

ILP helpful in organizing goals for career (Rate 1–5), no. (%)

 1-3 ratings	19 (40 %)	15 (60 %)	4 (17 %)

 4-5 ratings	29 (60 %)	10 (40 %)	19 (83 %)

Survey items	Overall (n=48)	‘No’ (n=25)	‘Yes’ (n=23)

ILP helpful in structuring ACE learning objectives (Rate 1–5), no. (%)

1-3 ratings	12 (25 %)	10 (40 %)	2 (9 %)

4-5 ratings	36 (75 %)	15 (60 %)	21 (91 %)

ILP helpful in organizing goals for career (Rate 1–5), no. (%)

1-3 ratings	19 (40 %)	15 (60 %)	4 (17 %)

4-5 ratings	29 (60 %)	10 (40 %)	19 (83 %)


Cumulative % variance	42.02	59.56	73.78a


Variable	HE group (n = 58)	Control group (n = 59)	P-value

Historical information

 Esophageal varices	60%	66%	0.518

 Variceal bleeding	21%	24%	0.693

 Variceal band ligation	24%	24%	0.952

Medications

 Non-selective beta blockers	36%	44%	0.386

 Narcotics	14%	8%	0.394

 Centrally acting medicationsa	41%	15%	0.002

 Diureticsb	88%	63%	0.002

Laboratory tests

 Na <135 mmol/L	69%	68%	0.892

 Creatinine > 1 mg/dL	31%	29%	0.793

CT scan findings

 Liver antero-posterior diameter ≤6 cm	91%	68%	0.001

 Liver cranio-caudal diameter ≤16 cm	69%	58%	0.203

 Spleen diameter ≥16 cm	47%	53%	0.517

 Nodular liver	86%	68%	0.018

 Caudate lobe hypertrophy	55%	64%	0.308

 Paraesophageal varices	67%	63%	0.608

 Splenorenal varices	72%	83%	0.166

 Umbilical vein recanalization	60%	58%	0.765

 Presence of ascites	55%	49%	0.515

 Portal vein diameter ≤12 mm	58%	28%	0.001

Duplex ultrasound findings

 Portal vein flow velocity <16 cm/s	26%	20%	0.475

 Hepatofugal flow	16%	7%	0.132

 Hepatic artery resistive index ≥0.75	33%	39%	0.527

Variable	HE group (n = 58)	Control group (n = 59)	P-value

Esophageal varices	60%	66%	0.518

Variceal bleeding	21%	24%	0.693

Variceal band ligation	24%	24%	0.952

Medications

Non-selective beta blockers	36%	44%	0.386

Narcotics	14%	8%	0.394

Centrally acting medicationsa	41%	15%	0.002

Diureticsb	88%	63%	0.002

Laboratory tests

Na <135 mmol/L	69%	68%	0.892

Creatinine > 1 mg/dL	31%	29%	0.793

CT scan findings

Liver antero-posterior diameter ≤6 cm	91%	68%	0.001

Liver cranio-caudal diameter ≤16 cm	69%	58%	0.203

Spleen diameter ≥16 cm	47%	53%	0.517

Nodular liver	86%	68%	0.018

Caudate lobe hypertrophy	55%	64%	0.308

Paraesophageal varices	67%	63%	0.608

Splenorenal varices	72%	83%	0.166

Umbilical vein recanalization	60%	58%	0.765

Presence of ascites	55%	49%	0.515

Portal vein diameter ≤12 mm	58%	28%	0.001

Duplex ultrasound findings

Portal vein flow velocity <16 cm/s	26%	20%	0.475

Hepatofugal flow	16%	7%	0.132

Hepatic artery resistive index ≥0.75	33%	39%	0.527


Variable	n	%

Surgical approach

 Laparoscopic, completely closed	20	90

 Hand-assisted laparoscopic	1	4.5

 Lap converted to open	1	4.5

No. of metastases resected	45

 1	14	64

 2	3	14

 ≥ 3	5	23

Segment of liver resected

 Combined segment 2 and 3	2	9

 Segment 3	8	36

 Segment 5	2	9

 Segment 6	8	36

 Segment 7	1	4.5

 Segment 8	1	4.5

Size (cm) of tumor resected (mean/median (range))	3.4/3 (0.3-8)

Operative specifics (mean/median (range))

 Intraoperative blood loss (mL)	256/100 (50–1400)

 Operative time (minutes)	194/193 (90–305)

 Use of pringle	3	14

 Parenchymal transection with ultrasonic device	21	95

 Parenchymal transection with endovascular stapler	15	68

Duration of hospitalization (days) (mean/median (range))	4/3 (1–10)

Postoperative complication	3	14

 Bile leak	1	4.5

 Rapid atrial fibrillation	1	4.5

 Colitis	1	4.5

Variable	n	%

Postoperative complication	3	14

Bile leak	1	4.5

Rapid atrial fibrillation	1	4.5

Colitis	1	4.5


ORF Clusters features	MFL x MHP*	MFL x MHR*	MFL x MHP x MHR*

OCs 100% conserved	44	17	12

OCs Partially conserved	44	35	33

OCs Without conservation	29	62	-

ORF Clusters features

OCs 100% conserved

OCs Partially conserved

OCs Without conservation

MFL x MHP*	MFL x MHR*	MFL x MHP x MHR*

44	17	12

44	35	33

29	62	-


Conceptualization	Description

Revolution	• Health’s increasing role in foreign policy is transformative of the health-foreign policy nexus• Health collapses the traditional distinction between high and low politics and creates a new political space in which health isan overriding normative value and the ultimate goal of foreign policy• Health is broadly conceived and encompasses the social determinants of health• Is consistent with health discourses that focus on health as a human right and the “health for all” ideal

Remediation	• Health’s rise as foreign policy issue reflects the continued persistence of the traditional hierarchy of foreign policy functions• Health has become another issue that needs to be addressed through traditional approaches to foreign policy, or as astrategic vehicle through which traditional foreign policy goals can be achieved• Foreign policy attention on health is focused when disease crises appear and fades when crises drop off the political spotlight•Provides the strongest explanation for why health has risen as a foreign policy issue

Regression	• Health’s integration into foreign policy is a regressive development – an indicator that health problems are getting worse• The increasing attention paid to health across the functions of foreign policy signifies the failure of public health efforts• Connecting health with the high politics of foreign policy threatens to tarnish long-standing associations of health withnormative values• Public health’s wish for health to become more politically prominent may have come true but in a way that threatens whatwas special about health in the first place

Conceptualization

Revolution

Remediation

Regression

Description

• Health’s increasing role in foreign policy is transformative of the health-foreign policy nexus• Health collapses the traditional distinction between high and low politics and creates a new political space in which health isan overriding normative value and the ultimate goal of foreign policy• Health is broadly conceived and encompasses the social determinants of health• Is consistent with health discourses that focus on health as a human right and the “health for all” ideal

• Health’s rise as foreign policy issue reflects the continued persistence of the traditional hierarchy of foreign policy functions• Health has become another issue that needs to be addressed through traditional approaches to foreign policy, or as astrategic vehicle through which traditional foreign policy goals can be achieved• Foreign policy attention on health is focused when disease crises appear and fades when crises drop off the political spotlight•Provides the strongest explanation for why health has risen as a foreign policy issue

• Health’s integration into foreign policy is a regressive development – an indicator that health problems are getting worse• The increasing attention paid to health across the functions of foreign policy signifies the failure of public health efforts• Connecting health with the high politics of foreign policy threatens to tarnish long-standing associations of health withnormative values• Public health’s wish for health to become more politically prominent may have come true but in a way that threatens whatwas special about health in the first place


	EU	Australia	Japan	WHO	Canada	Korea, India, Singapore, Malaysia

Synonym	Biosimilars	Biosimilars	Follow-on Biologics	Similar Biotherapeutic Product	Subsequent Entry Biologic	Biosimilars

Scope	Mainly recombinant protein drugs	Recombinant protein drugs

Principles	• Generic approach is not appropriate for SEB.

• SEB should be similar to the reference biologic with respect to quality, safety and efficacy.

• Step-wise comparability approach: the reduction of non-clinical and clinical data required will only be considered after the similarity of the SEB and reference biologic is proven in terms of quality.

• Case by case approach for different classes of products.

• Pharmacovigilance is stressed.

Reference product	Authorized in the EU	Authorized in Japan	Authorized in a region with a well-established regulatory framework

Manufacture	• Same standards required by the national regulatory agency for originator products.

• Full chemistry and manufacture data package.

Physio-chemical	• Primary and higher-order structure.

• Post translational modifications.

Purity	• Process-related and product-related impurities.

Non clinical	• In-vitro such as cell-based assays and receptor-binding studies.

Stability	Accelerated degradation studies and studied under various stress conditions	Not necessary	Accelerated degradation studies and studied under various stress conditions

Pharmacokinetic study design & criteria	• Single dose, steady-state studies or repeated determinations of pharmacokinetics

• Cross over or parallel.

• Include absorption and elimination characteristics.

• Use the traditional 80-125% equivalence range.

PD	Pharmacodynamic (PD) markers should be selected and comparative PK/PD studies may be appropriate

Efficacy	Comparability margins should be pre-specified and justified	Observer or double-blinded. Equivalence or non-inferiority	Equivalence

Safety/pharmacovigilance	• Pre-licensing safety data and risk management plan. Post authorization safety and/or efficacy studies may be required.

• Adverse reactions must be reported.

• Same rules apply to reference biologic and SEB.

INN vs. new generic name	INN	Unique generic name	Suffix “BS” added to INN	INN with biological qualifier (proposed)	INN but will follow WHO guidance	INN

Extrapolation of indications	• Assessed on a case-by-case basis.

• At least one clinical study required in the most sensitive population measuring the clinical endpoints likely to show a difference.

Principles	• SEB should be similar to the reference biologic with respect to quality, safety and efficacy.

• Step-wise comparability approach: the reduction of non-clinical and clinical data required will only be considered after the similarity of the SEB and reference biologic is proven in terms of quality.

• Case by case approach for different classes of products.

• Pharmacovigilance is stressed.

Reference product	Authorized in the EU	Authorized in Japan	Authorized in a region with a well-established regulatory framework

Manufacture	• Same standards required by the national regulatory agency for originator products.

• Full chemistry and manufacture data package.

Physio-chemical	• Primary and higher-order structure.

• Post translational modifications.

Purity	• Process-related and product-related impurities.

Non clinical	• In-vitro such as cell-based assays and receptor-binding studies.

Stability	Accelerated degradation studies and studied under various stress conditions	Not necessary	Accelerated degradation studies and studied under various stress conditions

Pharmacokinetic study design & criteria	• Single dose, steady-state studies or repeated determinations of pharmacokinetics

• Cross over or parallel.

• Include absorption and elimination characteristics.

• Use the traditional 80-125% equivalence range.

PD	Pharmacodynamic (PD) markers should be selected and comparative PK/PD studies may be appropriate

Efficacy	Comparability margins should be pre-specified and justified	Observer or double-blinded. Equivalence or non-inferiority	Equivalence

Safety/pharmacovigilance	• Pre-licensing safety data and risk management plan. Post authorization safety and/or efficacy studies may be required.

• Adverse reactions must be reported.

• Same rules apply to reference biologic and SEB.

INN vs. new generic name	INN	Unique generic name	Suffix “BS” added to INN	INN with biological qualifier (proposed)	INN but will follow WHO guidance	INN

Extrapolation of indications	• Assessed on a case-by-case basis.

• At least one clinical study required in the most sensitive population measuring the clinical endpoints likely to show a difference.


Pharmacovigilance area of interest

Activity type	Adverse events	Counterfeit drugs	Drug quality assurance	PV NOS	N/A	Total

 Behaviour change communication		6 (85.7)	1 (14.3)			7 (2.4)

 Improve regulatory system	1 (3.1)	6 (18.8)	14 (53.1)	11 (34.4)		32 (11.1)

 Improving supply chain		1 (6.7)	7 (46.7)	7 (46.7)		15 (5.2)

 Laboratory supplies and training		6 (15.4)	27 (69.2)	6 (15.4)		39 (13.5)

 Operations research	2 (66.7)		1 (33.3)			3 (1.0)

 Surveillance	3 (8.3)	10 (27.8)	21 (58.3)	2 (5.6)		36 (12.5)

 Training/capacity building		1 (9.1)	6 (54.5)	4 (36.4)		11 (3.8)

 Pharmacovigilance NOS	2 (6.3)	1 (3.1)	23 (71.9)	6 (18.8)		32 (11.1)

 Pharmacovigilance NOS-unfunded			26 (100)			26 (9.0)

 Surveillance-not funded	5 (100)					5 (1.7)

 Context onlya					39 (100)	39 (13.5)

 Historical activityb		12 (17.4)	37 (53.6)	17 (24.6)	3 (4.4)	69 (24.0)

 Total	14 (4.9)	40 (13.9)	154 (53.5)	49 (17.0)	42 (14.6)


Schizophrenic Patient Variables	Values

Schizophrenia Severity	Severe/Other

Schizophrenia Heavy Alcohol Use	Yes/No

Schizophrenia Heavy Drug Use	Yes/No

Schizophrenia	Paranoid/Undiff

Schizophrenia Sudden Death	Yes/No

Schizophrenia Suicide	Yes/No

Schizophrenia Lifetime Antipsychotics >45,000	Yes/No

Schizophrenia Antichollnergic	Yes/No

Schizophrenia Antidepressants	Yes/No

Schizophrenia Stabilizer	Yes/No

Schizophrenia Lithium	Yes/No

Schizophrenia Valproate	Yes/No

Schizophrenic Patient Variables	Values

Schizophrenia Lifetime Antipsychotics >45,000	Yes/No

Schizophrenia Antichollnergic	Yes/No

Schizophrenia Antidepressants	Yes/No

Schizophrenia Stabilizer	Yes/No

Schizophrenia Lithium	Yes/No

Schizophrenia Valproate	Yes/No


Reads	Assembler	Contig	Scaffold	Transf	Untransf	Shared	Masked

Sim	allp	57	7	21	1	18	12

Sim	sga_m75	504	463	NA	NA	NA	NA

Sim	sga_m77	513	479	NA	NA	NA	NA

Sim	soap_K69	1481	698	255	451	137	44

Sim	soap_K71	1469	769	NA	NA	NA	NA

Bs-1	allp	66	9	35	0	23	15

Bs-1	sga_m75	899	711	NA	NA	NA	NA

Bs-1	sga_m77	871	687	NA	NA	NA	NA

Bs-1	soap_K69	1916	670	365	429	210	95

Bs-1	soap_K71	1909	692	NA	NA	NA	NA

Reads	Assembler	Contig	Scaffold	Transf	Untransf	Shared	Masked

Bs-1	sga_m75	899	711	NA	NA	NA	NA

Bs-1	sga_m77	871	687	NA	NA	NA	NA

Bs-1	soap_K69	1916	670	365	429	210	95

Bs-1	soap_K71	1909	692	NA	NA	NA	NA


	Total	Diagnosis	Clinical therapy & drug resistance	Case reports	Vaccine development	Epidemiology	Health education	Interventions and control	Others

HIV/AIDS	24025 (100%)	1229 (5.1%)	2706 (11.3%)	2105 (8.7%)	561 (2.3%)	6243 (26.0%)	696 (2.9%)	1135 (4.7%)	9350 (39.0%)


Variable	Beclin 1 expression

All Cases	Low	High	p Value

HER2 expression in total cases(41)				0.008

Negative	26	21(80.8%)	5(19.2%)

Positive	15	6(40.0%)	9(60.0%)

HER2 expression in ER positive cases(25)				0.002

Negative	18	16(88.9%)	2(11.1%)

Positive	7	1(14.3%)	6(85.7%)

HER2 expression in ER negative cases(16)				1.000

Negative	8	5(62.5%)	3(37.5%)

Positive	8	5(62.5%)	3(37.5%)


Group of patients	Survivin positive	Survivin negative	Total

COX-2 positive	55	8	63

COX-2 negative	15	15	30

Total	70	23	93


Characteristic	Healthy volunteers	RA patients

	(N = 7)	(N = 10)

Age: mean (range)	56 (49–62)	63 (49–80)

Gender (% female)	43%	50%

Characteristic	Healthy volunteers	RA patients

	(N = 7)	(N = 10)

Gender (% female)	43%	50%


Line	Number of Individuals	Duplication	Deletion	HeR	Aneuploid	TOTAL

ACSRsyn1	16	2	2	0	0	4

Bronowski	16	0	1	0	0	1

Daichousen (fuku)	16	0	0	1	1	2

Maris Haplona	48	1	8	0	1	10

Surpass 400	16	0	0	0	0	0

Svalof’s Gulle	16	1	0	0	1	2

Tribune	16	2	2	0	1	5

Topas	16	0	1	0	1	2

PAK85912	46	5	4	5	3	17

Zhongyou821	48	3	2	0	4	9

Rainbow	254	12	22	30	13	77

Line	Number of Individuals

ACSRsyn1	16

Bronowski	16

Daichousen (fuku)	16

Maris Haplona	48

Surpass 400	16

Svalof’s Gulle	16

Tribune	16

Topas	16

PAK85912	46

Zhongyou821	48

Rainbow	254


Item	 	Number	Percent	Adjusted OR*	95% CI

A smoke-free hospital would improve the quality of care the patient receives (Agree)	Admin**	90	82.6%	1.0

Physicians	223	83.8%	1.4	0.63	3.1

 	Nurses	227	90.4%	2.2	0.84	5.7

Smoke from someone else's cigarette is unhealthy for non-smokers (Agree)	Admin	97	89.8%	1.0

Physicians	260	97.7%	4.6	1.41	15.1

 	Nurses	245	97.2%	3.6	1.04	12.6

The smoking habits of health professionals influence others (Agree)	Admin	100	91.7%	1.0

Physicians	258	97.0%	3.0	0.93	10.0

 	Nurses	236	93.7%	1.7	0.51	5.9

Cessation programs should be offered to employees (Agree)	Admin	101	92.7%	1.0

Physicians	254	95.5%	6.8	1.68	27.3

 	Nurses	239	95.2%	2.2	0.60	7.7

A hospital should be a smoke-free environment (Agree)	Admin	105	97.2%	1.0

Physicians	256	96.2%	1.2	0.30	4.6

 	Nurses	246	97.6%	1.4	0.27	7.4

Hospital employees who work in offices or areas removed from direct patient care should be allowed to smoke (Disagree)	Admin	76	69.7%	1.0

Physicians	196	73.7%	1.4	0.77	2.6

 	Nurses	155	61.3%	0.7	0.36	1.3

A smoke-free policy is hard to enforce (Disagree)	Admin	46	42.2%	1.0

Physicians	142	53.6%	2.1	1.28	3.5

 	Nurses	104	41.6%	1.2	0.66	2.0

Having a smoke-free policy is unfair to smokers (Disagree)	Admin	90	84.1%	1.0

Physicians	234	88.0%	2.6	1.08	6.1

 	Nurses	223	88.8%	1.2	0.47	3.1

Hospitals with smoke-free policies are likely to lose patients (Disagree)	Admin	86	79.6%	1.0

Physicians	205	77.1%	2.6	1.24	5.4

 	Nurses	186	73.5%	0.9	0.45	2.0

Smoking bans at hospitals would positively influence job performance (Agree)	Admin	59	54.6%	1.0

Physicians	190	71.7%	2.0	1.21	3.3

 	Nurses	190	75.7%	2.1	1.20	3.6

Smoking bans at hospitals would positively affect the public image of the hospital (Agree)	Admin	74	68.5%	1.0

Physicians	245	92.8%	5.5	2.79	10.8

 	Nurses	226	89.7%	3.3	1.63	6.6

Smoking bans at hospitals would positively affect the public image of the hospital (Agree)	Physicians	245	92.8%	5.5	2.79	10.8

	Nurses	226	89.7%	3.3	1.63	6.6


Rhomboid type	A Strepto

A Strepto	–

B Strepto	0.29474

C Strepto	0.35789

D Strepto	0.40001

E Strepto	0.43158

E Myco (Rv1337)	0.46316

AB Myco (Rv0110)	0.23158


Cytokine	Total papers	Total ratios	References

IL-4	6	7	Hensley et al., 2002, 2003; Kim et al., 2006; Beers et al., 2008; Chiu et al., 2008; Audet et al., 2012

IL-6	8	12	Hensley et al., 2002, 2003; Weydt et al., 2004; Xie et al., 2004; Kim et al., 2006; Chiu et al., 2008; Audet et al., 2012; Dibaj et al., 2012

IL-10	3	6	Hensley et al., 2002, 2003; Finkelstein et al., 2011

IL-1α	5	6	Hensley et al., 2003; Kiaei et al., 2006; Kim et al., 2006; Kassa et al., 2009; Neymotin et al., 2009

IL-1β	12	20	Hensley et al., 2003; Kang et al., 2003; Xie et al., 2004; Kiaei et al., 2006; Kim et al., 2006; Kassa et al., 2009; Neymotin et al., 2009; Fang et al., 2010; Zhao et al., 2010; Berger et al., 2011; Audet et al., 2012; Valente et al., 2012

IL-12	6	12	Hensley et al., 2002, 2003, 2006; Kiaei et al., 2006; Kim et al., 2006; Dibaj et al., 2012

TNF-α	18	39	Yoshihara et al., 2002; Hensley et al., 2003; Chen et al., 2004; Weydt et al., 2004; Xie et al., 2004; Perrin et al., 2005; Henkel et al., 2006; Kim et al., 2006; Zhang et al., 2008; Cheroni et al., 2009; Neymotin et al., 2009; Fang et al., 2010; Takeuchi et al., 2010; Finkelstein et al., 2011; Pollari et al., 2011; Audet et al., 2012; Valente et al., 2012

GFAP	46	164	Olsen et al., 2001; Yoshihara et al., 2002; Liu and Martin, 2006; Ohta et al., 2006; Pardo et al., 2006; Guan et al., 2007; Petrik et al., 2007; Yin et al., 2007; Beers et al., 2008; Pitzer et al., 2008; Poesen et al., 2008; Shibata et al., 2008; Boucherie et al., 2009; Cheroni et al., 2009; Kassa et al., 2009; Keller et al., 2009, 2011; Ringer et al., 2009; Sekiya et al., 2009; Yang et al., 2009, 2011; Guo et al., 2010, 2011; Israelsson et al., 2010; Jokic et al., 2010; Moreno-Igoa et al., 2010; Shimazawa et al., 2010; Steinacker et al., 2010; Suzuki et al., 2010; Tsai et al., 2010; Berger et al., 2011; Finkelstein et al., 2011; Genestine et al., 2011; Zhu and Sheng, 2011; Gifondorwa et al., 2012; Miquel et al., 2012; Valente et al., 2012

Type I total	56	241	Olsen et al., 2001; Hensley et al., 2002, 2003, 2006; Yoshihara et al., 2002; Kang et al., 2003; Chen et al., 2004; Weydt et al., 2004; Xie et al., 2004; Perrin et al., 2005; Henkel et al., 2006; Kiaei et al., 2006; Kim et al., 2006; Liu and Martin, 2006; Ohta et al., 2006; Pardo et al., 2006; Guan et al., 2007; Petrik et al., 2007; Yin et al., 2007; Beers et al., 2008; Pitzer et al., 2008; Poesen et al., 2008; Shibata et al., 2008; Zhang et al., 2008; Boucherie et al., 2009; Cheroni et al., 2009; Kassa et al., 2009; Keller et al., 2009, 2011; Neymotin et al., 2009; Ringer et al., 2009; Sekiya et al., 2009; Yang et al., 2009, 2011; Fang et al., 2010; Guo et al., 2010, 2011; Israelsson et al., 2010; Jokic et al., 2010; Moreno-Igoa et al., 2010; Shimazawa et al., 2010; Steinacker et al., 2010; Suzuki et al., 2010; Takeuchi et al., 2010; Tsai et al., 2010; Zhao et al., 2010; Berger et al., 2011; Finkelstein et al., 2011; Genestine et al., 2011; Pollari et al., 2011; Audet et al., 2012; Dibaj et al., 2012; Gifondorwa et al., 2012; Miquel et al., 2012; Valente et al., 2012

Type II total	10	25	Hensley et al., 2002, 2003; Weydt et al., 2004; Xie et al., 2004; Kim et al., 2006; Beers et al., 2008; Chiu et al., 2008; Finkelstein et al., 2011; Audet et al., 2012; Dibaj et al., 2012

Cytokine	Total papers	Total ratios	References

IL-1β	12	20	Hensley et al., 2003; Kang et al., 2003; Xie et al., 2004; Kiaei et al., 2006; Kim et al., 2006; Kassa et al., 2009; Neymotin et al., 2009; Fang et al., 2010; Zhao et al., 2010; Berger et al., 2011; Audet et al., 2012; Valente et al., 2012

IL-12	6	12	Hensley et al., 2002, 2003, 2006; Kiaei et al., 2006; Kim et al., 2006; Dibaj et al., 2012

TNF-α	18	39	Yoshihara et al., 2002; Hensley et al., 2003; Chen et al., 2004; Weydt et al., 2004; Xie et al., 2004; Perrin et al., 2005; Henkel et al., 2006; Kim et al., 2006; Zhang et al., 2008; Cheroni et al., 2009; Neymotin et al., 2009; Fang et al., 2010; Takeuchi et al., 2010; Finkelstein et al., 2011; Pollari et al., 2011; Audet et al., 2012; Valente et al., 2012

GFAP	46	164	Olsen et al., 2001; Yoshihara et al., 2002; Liu and Martin, 2006; Ohta et al., 2006; Pardo et al., 2006; Guan et al., 2007; Petrik et al., 2007; Yin et al., 2007; Beers et al., 2008; Pitzer et al., 2008; Poesen et al., 2008; Shibata et al., 2008; Boucherie et al., 2009; Cheroni et al., 2009; Kassa et al., 2009; Keller et al., 2009, 2011; Ringer et al., 2009; Sekiya et al., 2009; Yang et al., 2009, 2011; Guo et al., 2010, 2011; Israelsson et al., 2010; Jokic et al., 2010; Moreno-Igoa et al., 2010; Shimazawa et al., 2010; Steinacker et al., 2010; Suzuki et al., 2010; Tsai et al., 2010; Berger et al., 2011; Finkelstein et al., 2011; Genestine et al., 2011; Zhu and Sheng, 2011; Gifondorwa et al., 2012; Miquel et al., 2012; Valente et al., 2012

Type I total	56	241	Olsen et al., 2001; Hensley et al., 2002, 2003, 2006; Yoshihara et al., 2002; Kang et al., 2003; Chen et al., 2004; Weydt et al., 2004; Xie et al., 2004; Perrin et al., 2005; Henkel et al., 2006; Kiaei et al., 2006; Kim et al., 2006; Liu and Martin, 2006; Ohta et al., 2006; Pardo et al., 2006; Guan et al., 2007; Petrik et al., 2007; Yin et al., 2007; Beers et al., 2008; Pitzer et al., 2008; Poesen et al., 2008; Shibata et al., 2008; Zhang et al., 2008; Boucherie et al., 2009; Cheroni et al., 2009; Kassa et al., 2009; Keller et al., 2009, 2011; Neymotin et al., 2009; Ringer et al., 2009; Sekiya et al., 2009; Yang et al., 2009, 2011; Fang et al., 2010; Guo et al., 2010, 2011; Israelsson et al., 2010; Jokic et al., 2010; Moreno-Igoa et al., 2010; Shimazawa et al., 2010; Steinacker et al., 2010; Suzuki et al., 2010; Takeuchi et al., 2010; Tsai et al., 2010; Zhao et al., 2010; Berger et al., 2011; Finkelstein et al., 2011; Genestine et al., 2011; Pollari et al., 2011; Audet et al., 2012; Dibaj et al., 2012; Gifondorwa et al., 2012; Miquel et al., 2012; Valente et al., 2012

Type II total	10	25	Hensley et al., 2002, 2003; Weydt et al., 2004; Xie et al., 2004; Kim et al., 2006; Beers et al., 2008; Chiu et al., 2008; Finkelstein et al., 2011; Audet et al., 2012; Dibaj et al., 2012


Factor	Adjusted OR	95% CI	P value

Age	1.032	0.991–1.075	0.129 (NS)

Gender

Female	1

Male	0.341	0.083–1.402	0.136 (NS)

Bedbound

No	1

		0.419–1	0.173 (N


Formulation (%)/treatment	T1	T2	T3

TV surimi	91.25	–	–

MSTM surimi	–	76.25	91.25

Cold water	–	15.00	–

Soybean-concentrated protein	4.00	4.00	4.00

Cassava starch	2.00	2.00	2.00

Cure salt	0.25	0.25	0.25

Global sausage SV 800	0.80	0.80	0.80

Cochonilha carmim	0.05	0.05	0.05

Refined salt	1.65	1.65	1.65

Formulation (%)/treatment	T1

TV surimi	91.25

MSTM surimi	–

Cold water	–

Soybean-concentrated protein	4.00

Cassava starch	2.00

Cure salt	0.25

Global sausage SV 800	0.80

Cochonilha carmim	0.05

Refined salt	1.65


N	Multiplicative Model	Additive Model

Coefficient	Value	SE	Units	Coefficient	Value	SE	Units

389	b *	0.0021	3.4 × 10−5	°C−1 d−1	b	0.0024	3.8 × 10−5	°C−1 d−1

389	g * (plus)	9.464	1.080	dh−1	g (plus)	11.40	0.983	dh−1

389	g * (neg)	−9.822	1.078	dh−1	g (neg)	−11.02	0.921	dh−1


Attribute	Value	% of Total

Genome size (bp)	4,024,382	100.00%

DNA coding region (bp)	3,618,708	89.92%

DNA G+C content (bp)	2,845,385	70.70%

Number of replicons	1

Extrachromosomal elements	0

Total genes	3,710	100.00%

RNA genes	57	1.54%

rRNA operons	2

Protein-coding genes	3,653	98.46%

Pseudo genes	90	2.43%

Genes with function prediction	2,645	71.29%

Genes in paralog clusters	360	7.70%

Genes assigned to COGs	2,674	72.08%

Genes assigned Pfam domains	2,871	77.39%

Genes with signal peptides	1,101	29.68%

Genes with transmembrane helices	860	23.18%

CRISPR repeats	0

Attribute	Value	% of Total

Genome size (bp)	4,024,382	100.00%

DNA coding region (bp)	3,618,708	89.92%

DNA G+C content (bp)	2,845,385	70.70%

Number of replicons	1

Extrachromosomal elements	0

Total genes	3,710	100.00%

RNA genes	57	1.54%

rRNA operons	2

Protein-coding genes	3,653	98.46%

Pseudo genes	90	2.43%

Genes with function prediction	2,645	71.29%

Genes in paral	3

Attribute	Value	% of Total

og clusters	60	7.70%

Genes assigned to COGs	2,674	72.08%

Genes assigned Pfam domains	2,871	77.39%

Genes with signal peptides	1,101	29.68%

Genes with transmembrane helices	860	23.18%

CRISPR repeats	0


 Group	Dose (mg/kg)	Sleep latency (min)	Sleeping time (min)

Normal	60	8 ± 1	36 ± 3

 DZP	 3	6 ± 1*	75 ± 3*

 ME	 800	12 ± 0.5*	45 ± 2*

 ME	 1000	6 ± 1*	112 ± 3*


	Median (Inter-quartile range) or N (%)	*p-value

Variables	HCC (n = 62)	Non-HCC (n = 57)

Age (years)	49.5(35–55)	36(32–51)	p = 0.05