Treatment	Flume number	Field name

Sustainable intensification	6	Golden Rove

Increased use of legumes	8	Higher Wyke Moor and Middle Wyke Moor (reseeding in 2013)

11	Dairy East

Planned reseeding	10	Lower Wheaty

15	Longlands East (reseeding in 2013)

Treatment	Flume number	Field name

Sustainable intensification	6	Golden Rove

Increased use of legumes	8	Higher Wyke Moor and Middle Wyke Moor (reseeding in 2013)

11	Dairy East

	10	Lower Whea

Planned reseeding		ty

15	Longlands East (reseeding in 2013)


Characteristics	Count (%)

Sociodemographic

 Gender

Male	98 (65.3)

Female	52 (34.7)

 Age (years)

20–30	80 (53.3)

31–40	48 (32.0)

41–50	22 (14.7)

 Education level

Vocational school	58 (38.7)

Diploma or equivalent	62 (41.3)

Bachelor degree or higher	30 (20.0)

 Monthly income (Baht)

<9000	96 (64.0)

≥9000	54 (36.0)

Behavioral

 Smoke cigarettes

No	70 (46.7)

Yes	80 (53.3)

 Drink alcohol

No	86 (57.3)

Yes	64 (42.7)

Characteristics	Count (%)

41–50	22 (14.7)

Education level

Vocational school	58 (38.7)

Diploma or equivalent	62 (41.3)

Bachelor degree or higher	30 (20.0)

Monthly income (Baht)

<9000	96 (64.0)

≥9000	54 (36.0)

Behavioral

Smoke cigarettes

No	70 (46.7)

Yes	80 (53.3)

Drink alcohol

No	86 (57.3)

Yes	64 (42.7)


Variable	PIK3CA mutations (n = 113)

	Yes	No	P

No.of patients	8	105

Gender

Male	5	82	0.57

Female	3	23

Age, years

Mean	55.5	59.1	0.47

SD	19.8	12.7

Tumor localization

gastric cardia	0	26	0.98

gastric body	5	24

gastric antrum	3	55

Tumor size (cm3)

≤ 3	3	35	0.68

3-5	3	35

> 5	2	35

Differentiation

well/moderate	1	44	0.21

poor/undifferentiation	7	61

Tumor invasion

T1	2	14	0.96

T2	0	17

T3	6	72

T4	0	2

TNM stage

I	2	27	0.91

II	1	14

III	5	58

IV	0	6

Residual tumor

Yes	1	12	1.00

No	7	93

Lymph node metastasis (LNM)

Yes	5	65	1.00

No	3	40

No. of LNM

N0	3	40	0.63

N1 (1-6)	4	36

N2 (7-15)	1	23

N3 (≥ 16)	0	6

Survival status

Dead	3	53	0.73

Alive	5	52


		Parametric	Nonparametric

Misacylation

	COVE	68*	55

	resCOVE	64	64

	Spacer	55	64

	Usage	38	48

COVERes COVE

	Spacer	46	46

		64	73*

	Usage	67	62

		57	52

Spacer	Usage	55	55

Processing	Misacylation		82*/46

	COVE		82*/82*

	res COVE		55/55

	Mis-COVE	82*/46	64/55

	Mis-res COVE	73*/55	64/55

	Mis-Usage	55/20	64/30

	COVE-Usage	55/90*	55/80*

	Res COVE-Usage	46/80*	46/70


 Age/sex	Comorbidity	Site	Culture source	Therapy	Outcome

75/F	Syringomyelia	L leg	Tissue	Antibiotics, debridement	Survived

80/F	None	R leg	Tissue	Antibiotics, debridement	Survived (skin graft)

49/F	None	L ankle	Tissue	Antibiotics, debridement	Survived

75/M	None	R leg	Tissue	Antibiotics, debridement	Survived

71/M	None	L foot	Skin/bulla	Antibiotics, debridement	Survived (skin graft)

59/M	Not stated	R leg	Skin/blister	Antibiotics, debridement	Died

64/F	Diabetes mellitus	Both legs	Tissue	Antibiotics	Died

65/F	Rheumatoid arthritis	R arm	Blood/tissue	Antibiotics, amputation	Died

52/M	Diabetes mellitus	R leg	Tissue	Antibiotics, debridement	Survived

52/M	Diabetes mellitus	R leg	Tissue	Antibiotics, debridement	Survived

59/M	Hairy-cell leukemia	L leg	Blood/tissue	Antibiotics, debridement	Survived

58/M	Cirrhosis	L leg	Tissue	Antibiotics, debridement	Died

49/F	Rheumatoid arthritis	R leg	Blood/skin	Antibiotics	Died

48/M	None	R leg	Tissue	Antibiotics, debridement	Survived

77/F	Rheumatoid arthritis	R leg	Tissue/blood	Antibiotics	Died

2/M	Vascular/lymphatic malformation	Perineum	Tissue/stool	Antibiotics, debridement	Survived

Age/sex	Comorbidity	Site	Culture source	Therapy	Outcome

2/M	Vascular/lymphatic malformation	Perineum	Tissue/stool	Antibiotics, debridement	Survived


Outcome	All births

	n	Rate	OR (95% CI)	AORa (95% CI)

Umbilical artery pH < 7.10

 Occiput posterior	56	5.5	1.48 (1.12–1.96)	1.28 (0.93–1.74)

 Occiput anterior	733	3.8	reference	reference

Metabolic acidaemia

 Occiput posterior	2	0.2	1.15 (0.28–4.80)	0.64 (0.08–5.04)

 Occiput anterior	33	0.2	reference	reference

Apgar score < 7 at 5 min

 Occiput posterior	20	1.5	2.18 (1.37–3.47)	1.84 (1.11–3.05)

 Occiput anterior	188	0.7	reference	reference

Neonatal care

 Occiput posterior	38	2.9	1.87 (1.33–2.62)	1.68 (1.17–2.42)

 Occiput anterior	420	1.6	reference	reference

Composite morbidityb

 Occiput posterior	47	3.6	1.87 (1.38–2.54)	1.66 (1.19–2.31)

 Occiput anterior	520	2.0	reference	reference

Outcome	All births

	n	Rate	OR (95% CI)	AORa (95% CI)

Neonatal care

Occiput posterior	38	2.9	1.87 (1.33–2.62)	1.68 (1.17–2.42)

Occiput anterior	420	1.6	reference	reference

Composite morbidityb

Occiput posterior	47	3.6	1.87 (1.38–2.54)	1.66 (1.19–2.31)

Occiput anterior	520	2.0	reference	reference


Material	Scaffold Preparation	Shape and Structure of the Scaffold	Mechanical Properties of the Scaffold	Ref.

Collagen	Freeze drying	Sponges L = 11, 23 or 51 mm94% porosity, pore size = 62 μm	For L = 23 mm spec. EM = 0.02 MPaLinear Stiffness = 0.05 N/mmMaximum Stress = 0.005 MPa	[38,39]

Collagen/Chondroitin Sulfate	Sponge pore size = 53 μm	Linear Stiffness = 0.025 N/mm	[87]

Collagen/Chondroitin Sulfate	Isotropic sponge pore size = 87 μmAnisotropic pore sizes = 55, 152, 243 μm	ND	[51,55]

Collagen	Extrusion	EDC Crosslinked fiber diameter = 215 μmEDC/EDGE Crosslink diameter = 137 μm	Fiber diameter 215 μm → EM = 19.3 MPaFiber diameter 137 μm → EM = 46.2 MPa	[52,53]

Collagen	ELAC	Collagen thread diameter = 50–100 μm	ND	[33]

Collagen	Woven collagen scaffold with 81% of porosity	Stiffness = 23.8 N/mm	[34]

PLGA	Electrospinning	Random nanofibers = 568 nmAligned fibers = 320, 680 and 1800 nm	Random nanofibers → EM = 107 MPaAligned fibers → EM = 341–510 MPa	[105,106]

PLLA	Aligned nanofiber diameter = 430 nmRandom nanofiber diameter = 450 nm	Aligned nanofibers → Stiffness = 3.48 N/mm; EM = 22.76 MPaRandom nanofibers → Stiffness = 0.07 N/mm; EM = 0.63 MPa	[30]

PLDLLA	Crimped fiber diameter = 880 nmAmplitude = 5.2 μmWavelength = 46 μm	Crimped fiber Modulus = 3 MPa	[54]

PEEUR	Aligned or random fiberdiameters <1 μm, 1–2 μm or >2 μm	EM = 4.2–9.2 MPa	[45,46]

PCL	Yarned made of twisted aligned fibers (200 μm diameter)	UTS = 17 MPaEM = 30 MPa	[35]

P(LLA-CL)/Collagen	Fiber diameter = 643 nmFinal yarn thickness = 150 μmPore size = 28.5 μm	Yarns EM = 2 MPaUltimate deformation = 250%	[107]

PLGA	Knitting	Scaffold with 3 yarns. 20 filaments/yarn25 μm diameter of filament + electrospun nanofibers	Initial failure load = 56.3 NInitial Elastic Stiffness = 5.80 N/mmInitial toe region Stiffness = 0.34 N/mm	[36]

Silk	Combined knitted silk fibers and silk sponge pores size from 20 to 100 μm	Maximum Tensile Load = 252 NTensile Stiffness = 40 N/mm	[37]

Silk/Collagen	Combined knitted silk scaffold and freeze dryed collagen sponge	Failure force = 21.65 N	[97]

Material	Scaffold Preparation	Shape and Structure of the Scaffold	Mechanical Properties of the Scaffold	Ref.

Collagen	Freeze drying	Sponges L = 11, 23 or 51 mm94% porosity, pore size = 62 μm	For L = 23 mm spec. EM = 0.02 MPaLinear Stiffness = 0.05 N/mmMaximum Stress = 0.005 MPa	[38,39]

Collagen/Chondroitin Sulfate	Sponge pore size = 53 μm	Linear Stiffness = 0.025 N/mm	[87]

Collagen/Chondroitin Sulfate	Isotropic sponge pore size = 87 μmAnisotropic pore sizes = 55, 152, 243 μm	ND	[51,55]

Collage	Extr	EDC Crosslinked fiber diameter = 215 μmEDC/EDGE Crosslink diame	Fiber diam	[52,53

n	usion	ter = 137 μm	eter 215 μm → EM = 19.3 MPaFiber diameter 137 μm → EM = 46.2 MPa	]

Collagen	ELAC	Collagen thread diameter = 50–100 μm	ND	[33]

Collagen	Woven collagen scaffold with 81% of porosity	Stiffness = 23.8 N/mm	[34]

PLGA	Electrospinning	Random nanofibers = 568 nmAligned fibers = 320, 680 and 1800 nm	Random nanofibers → EM = 107 MPaAligned fibers → EM = 341–510 MPa	[105,106]

PLLA	Aligned nanofiber diameter = 430 nmRandom nanofiber diameter = 450 nm	Aligned nanofibers → Stiffness = 3.48 N/mm; EM = 22.76 MPaRandom nanofibers → Stiffness = 0.07 N/mm; EM = 0.63 MPa	[30]

PLDLLA	Crimped fiber diameter = 880 nmAmplitude = 5.2 μmWavelength = 46 μm	Crimped fiber Modulus = 3 MPa	[54]

PEEUR	Aligned or random fiberdiameters <1 μm, 1–2 μm or >2 μm	EM = 4.2–9.2 MPa	[45,46]

PCL	Yarned made of twisted aligned fibers (200 μm diameter)	UTS = 17 MPaEM = 30 MPa	[35]

P(LLA-CL)/Collagen	Fiber diameter = 643 nmFinal yarn thickness = 150 μmPore size = 28.5 μm	Yarns EM = 2 MPaUltimate deformation = 250%	[107]

PLGA	Knitting	Scaffold with 3 yarns. 20 filaments/yarn25 μm diameter of filament + electrospun nanofibers	Initial failure load = 56.3 NInitial Elastic Stiffness = 5.80 N/mmInitial toe region Stiffness = 0.34 N/mm	[36]

Silk	Combined knitted silk fibers and silk sponge pores size from 20 to 100 μm	Maximum Tensile Load = 252 NTensile Stiffness = 40 N/mm	[37]

Silk/Collagen	Combined knitted silk scaffold and freeze dryed collagen sponge	Failure force = 21.65 N	[97]


Demographic characteristics	Sampled frequency, n (%)	Weight misperception frequency, n (%)

Sexa

 Female	2003 (44.5)	426 (21.4)

 Male	2380 (55.5)	900 (39.1)

Race/ethnicityb

 American Indian/Alaskan Native	50 (0.6)	17 (30.7)

 Asian	111 (2.2)	33 (20.8)

 Hispanic/Latino	1672 (25.3)	457 (28.3)

 Multiple Race/Ethnicities Non-Hispanic	223 (5.1)	67 (23.3)

 Native Hawaiian/other Pacific Islander	29 (0.6)	8 (37.2)

 Non-Hispanic black or African American	479 (14.5)	202 (41.0)

 Non-Hispanic white	1819 (51.8)	542 (31.0)

Grade in schoolc

 9th	1120 (26.4)	376 (35.6)

 10th	1129 (26.6)	357 (30.7)

 11th	1152 (24.3)	330 (30.2)

 12th	982 (22.7)	263 (27.7)


	Men (n = 58)	Women (n = 65)	ANOVA	F	p

Ben


Task	Group description	Activity of group 1 higher that group 2	Activity of group 1 low that group 2	Reference

Tactile stimulation	PD patients (1) vs. healthy control volunteers	R. primary sensory, R. motor cortex, R. supplementary motor area, B. caudate, B. precuneus, B. occipital visual cortex, L. and M. temporal gyrus		(23)

Time perception task	PD patients (1) vs. healthy control volunteers and medical patients (2)	Precuneus (after long stimuli)		(26)

Gambling	Non-Pathological gamblers whit PD (1) vs. Pathological gamblers with PD (2)	B. anterior cingulate cortex, M. and S. frontal gyri, precuneus, R. I. parietal lobule, ventral striatum		(24)

Imaginary gait	PD patients experiencing freezing (1) vs. PDs not experiencing freezing (2)	R. globus pallidus, R. supplementary motor area, R. mesencephalic locomotor region, R. cerebellum, B. anterior insula, B. ventral striatum, B. pre-supplementary motor area, L. sub-thalamic nucleaus		(28, 29)

Hand movement	PD patients with (1) and without (2) mirror movements syndrome	R. dorsolateral prefrontal cortex, M. prefrontal cortex, Pre-supplementary motor area, Occipital Cortex	B. insula, B. posterior cingulate cortex, L inferior frontal cortex	(27)

Balloon analog risk task	PD patients with an impulse-control disorder (1) vs. PD patients without and impulse-control disorder (2)	R. ventral striatum		(25)

Speech	PD patients (1) vs. healthy control volunteers	Primary orofacial sensorimotor cortex		(20)

Saccade	PD patients (1) vs. healthy control volunteers	Frontal and supplementary eye fields	L. and R. cerebellum contralateral motor cortex	(22)

Finger tapping	PD patients (1) vs. healthy control volunteers	Putamen, supplementary motor area	R. prefrontal cortex, R. caudate	(21)

Task	Group description	Activity of group 1 higher that group 2

Tactile stimulation	PD patients (1) vs. healthy control volunteers	R. primary sensory, R. motor cortex, R. supplementary motor area, B. caudate, B. precuneus, B. occipital visual cortex, L. and M. temporal gyrus

Time perception task	PD patients (1) vs. healthy control volunteers and medical patients (2)	Precuneus (after long stimuli)

Gambling	Non-Pathological gamblers whit PD (1) vs. Pathological gamblers with PD (2)	B. anterior cingulate cortex, M. and S. frontal gyri, precuneus, R. I. parietal lobule, ventral striatum

Imaginary gait	PD patients experiencing freezing (1) vs. PDs not experiencing freezing (2)	R. globus pallidus, R. supplementary motor area, R. mesencephalic locomotor region, R. cerebellum, B. anterior insula, B. ventral striatum, B. pre-supplementary motor area, L. sub-thalamic nucleaus

Hand movement	PD patients with (1) and without (2) mirror movements syndrome	R. dorsolateral prefrontal cortex, M. prefrontal cortex, Pre-supplementary motor area, Occipital Cortex

Balloon analog risk task	PD patients with an impulse-control disorder (1) vs. PD patients without and impulse-control disorder (2)	R. ventral striatum

Speech	PD patients (1) vs. healthy control volunteers	Primary orofacial sensorimotor cortex

Saccade	PD patients (1) vs. healthy control volunteers	Frontal and supplementary eye fields

Finger tapping	PD patients (1) vs. healthy control volunteers	Putamen, supplementary motor area

Activity of group 1 low that group 2	Reference

	(23)

	(26)

	(24)

	(28, 29)

B. insula, B. posterior cingulate cortex, L inferior frontal cortex	(27)

	(25)

	(20)

L. and R. cerebellum contralateral motor cortex	(22)

R. prefrontal cortex, R. caudate	(21)


Motor nerve conduction

Nerve	Latency	Amplitude	Conduction velocity

Median R (wrist)	8.9 ms	1.3 mV

Median R (elbow)	18.5 ms	0.8 mV	24 m/s

Ulnar R (wrist)	4.4 ms	6.9 mV

Ulnar R (below elbow)	10.4 ms	5.7 mV	38 m/s

Ulnar R (above elbow)	13.4 ms	3.3 mV	33 m/s

Tibial R (ankle)	6.2 ms	3.4 mV

Tibial R (popliteal fossa)	23.1 ms	0.7 mV	24 m/s

Motor nerve conduction

Nerve	Latency	Amplitude	Conduction velocity

Median R (	8	1.3

wrist)	.9 ms	 mV

Median R (elbow)	18.5 ms	0.8 mV	24 m/s

Ulnar R (wrist)	4.4 ms	6.9 mV

Ulnar R (below elbow)	10.4 ms	5.7 mV	38 m/s

Ulnar R (above elbow)	13.4 ms	3.3 mV	33 m/s

Tibial R (ankle)	6.2 ms	3.4 mV

Tibial R (popliteal fossa)	23.1 ms	0.7 mV	24 m/s


	No. of abnormalities

Abnormality	Arctic	Innoko	Kenai	Tetlin	Yukon Delta	Total

Eye abnormality

 Anophthalmia (missing eye)	0	2	12	6	0	20

 Unpigmented iris (black eye)	0	15	118	20	1	154

 Microphthalmia (small eye)	0	0	1	1	0	2

 Othera	0	2	6	2	0	10

Skeletal injuryb

 Brachydactyly (short digits)	2	0	7	0	2	11

 Ectrodactyly (missing digits)	1	1	4	3	0	9

 Ectromelia (partial limb)	0	0	44	6	0	50

 Limb crushed	0	0	14	1	2	17

 Otherc	0	2	2	0	0	4

Skeletal malformation

 Amelia (missing limb)	0	1	31	3	0	35

 Anteversion (twisted long bones)	0	0	9	0	0	9

 Brachygnathia (short jaw)	1	4	6	0	0	11

 Microcephaly (shrunken head or blunt snout)	0	0	4	0	0	4

 Micromelia (shrunken limb or limb element)	5	3	126	17	3	154

 Polymelia (extra limb)	0	0	1	0	0	1

 Polydactyly (extra digits)	2	0	2	0	0	4

 Scoliosis or lordosis (curved spine)	0	0	2	0	0	2

 Cutaneous fusion (skin webbing)	0	0	3	0	0	3

 Syndactyly (digits fused)	0	0	11	2	0	13

 Taumelia (bone bridge or triangle)	0	0	4	0	0	4

Skeletal unknown origin

 Kinked tail	0	0	3	0	0	3

 Brachydactyly (short digits)	0	1	27	1	2	31

 Ectrodactyly (missing digits)	0	0	26	3	0	29

 Ectromelia (partial limb)	7	12	90	14	2	125

 Otherd	0	2	5	0	0	7

Overall

 Eye total	0	19	137	29	1	186

 Injury total	3	3	71	10	4	91

 Malformation total	8	8	199	22	3	240

 Unknown origin total	7	15	151	18	4	195

Total abnormalities	18	45	558	79	12	712

Total abnormal individuals	12	39	450	68	7	576

Total individuals examined	615	1,309	5,716	1,146	482	9,268

Percent individuals abnormal	2.0%	3.0%	7.9%	5.9%	1.5%	6.2%

	No. of abnormalities

Abnormality	Arctic

Eye abnormality

Anophthalmia (missing eye)	0

Unpigmented iris (black eye)	0

Microphthalmia (small eye)	0

Othera	0

Skeletal injuryb

Brachydactyly (short digits)	2

Ectrodactyly (missing digits)	1

Ectromelia (partial limb)	0

Limb crushed	0

Otherc	0

Skeletal malformation

Amelia (missing limb)	0

Anteversion (twisted long bones)	0

Brachygnathia (short jaw)	1

Microcephaly (shrunken head or blunt snout)	0

Micromelia (shrunken limb or limb element)	5

Polymelia (extra limb)	0

Polydactyly (extra digits)	2

Scoliosis or lordosis (curved spine)	0

Cutaneous fusion (skin webbing)	0

Syndactyly (digits fused)	0

Taumelia (bone bridge or triangle)	0

Skeletal unknown origin

Kinked tail	0

Brachydactyly (short digits)	0

Ectrodactyly (missing digits)	0

Ectromelia (partial limb)	7

Otherd	0

Overall

Eye total	0

Injury total	3

Malformation total	8

Unknown origin total	7

Total abnormalities	18

Total abnormal individuals	12

Total individuals examined	615

Percent individuals abnormal	2.0%


	pCR prediction(n = 488)

Prediction evaluation*	PPV (SD)	NPV (SD)	Sensitivity (SD)	Specificity (SD)

Unsupervised clustering

BRmet50	93(14)	34(3)	58(3)	83(0.6)

PMID18271932Sig33	92(3)	32(5)	53(6)	83(6)

Anthracycline-taxane Centroid

BRmet50	89(6)	27(0.6)	40(5)	83(6)

PMID18271932Sig33	77(4)	20(3)	29(1)	67(0.5)

	pCR prediction(n = 488)

Prediction evaluation*	PPV (SD)	NPV (SD)	Sensitivity (SD)

Unsupervised clustering

BRmet50	93(14)	34(3)	58(3)

PMID18271932Sig33	92(3)	32(5)	53(6)

Anthracycline-taxane Centroid

BRmet50	89(6)	27(0.6)	40(5)

PMID18271932Sig33	77(4)	20(3)	29(1)


SNP ID	Chr 16 position sequence	Sequence	Type	Amino acid change

rs200158701	70680854(+)	CCATGC/TCCCGG	mis	PS

rs192337001	70680866(+)	GCTTCA/CCCTGG	mis	TP

rs139133476	70688459(+)	CCTTGG/CCGTGG	mis	AG

rs142890682	70688461(+)	TTGGCG/ATGGCC	mis	MV

rs118062333	70690511(+)	AACACT/CACTTC	mis	HY

rs200597979	70690960(+)	GGGCCA/GCCCAT	mis	HR

rs8046424	70690989(+)	AGGTGC/GAGACG	mis	QE

rs187166563	70693576(+)	CCCAGA/GGCCAA	mis	EG

rs142214904	70693626(+)	GCTTCC/TGGGTC	mis	RW

rs7206509	70693945(+)	GCCAAG/CTCCTC	mis	TS

rs201277640	70693984(+)	GTATGC/TGGCCA	mis	AV

rs202122982	70694001(+)	TGTACC/TCTCCG	mis	PS

rs148286339	70694011(+)	GCCCCC/TGTGGT	mis	PL

rs141513638	70694056(+)	GAGGCC/TGGTCA	mis	PL

rs112639369	70694073(+)	AGGGCG/AAGGGC	mis	KE

rs1444643201	70694076(+)	GCGAGG/AGCCTC	mis	SG

rs367851338	70693627(+)	CTTCCA/GGGTCA	mis	QR

rs368143418	70690933(+)	TGAGTC/TGGTGC	mis	SL

rs374665339	70690963(+)	CCACCC/TATCCT	mis	PL

rs368923655	70691023(+)	CCTCAC/TGGTGA	mis	TM

rs368367274	70693597(+)	GGTGCA/GGCCCA	mis	QR

rs200891924	70693560(+)	TGTCCC/ATCTTG	mis	IL


Groups	Total cholesterol 	LDL-C	HDL-C	TG	HbA1c	FBG

r Pearson	r Pearson	r Pearson	r Pearson	r Pearson	r Pearson

Ox-LDL of normoalbuminurics	−0.07	−0.085	−0.25	−0.21	−0.024	−0.220

Ox-LDL of microalbuminurics	−0.086	−0.2	−0.28	0.28	−0.379	0.36

Ox-LDL of macroalbuminurics	−0.148	0.066	0.001	−0.139	−0.136	−0.129

Ox-LDL of first degree relatives	 −0.26	0.21	−0.029	0.26	0.03	−0.093

Ox-LDL of control group	0.49	0.33	0.092	0.05	0.057	−0.37

ps	 cholesterol	L-C			A1c	FBG

r Pearson	r Pearson	r Pearson	r Pearson	r Pearson	r Pearson

Ox-LDL of normoalbuminurics	−0.07	−0.085	−0.25	−0.21	−0.024	−0.220

Ox-LDL of microalbuminurics	−0.086	−0.2	−0.28	0.28	−0.379	0.36

Ox-LDL of macroalbuminurics	−0.148	0.066	0.001	−0.139	−0.136	−0.129

Ox-LDL of first degree relatives	−0.26	0.21	−0.029	0.26	0.03	−0.093

Ox-LDL of control group	0.49	0.33	0.092	0.05	0.057	−0.37


	Survivors(n = 90)	Former prisoners(n = 83)

Gender % (n)

Male	28.9 (26)	90.2 (74)

Female	71.1 (64)	9.8 (8)

Age	51.6 (10.3, 30–77)	53.9 (7.9, 34–81)

Marital Status % (n)

Single	4.5 (4)	1.2 (1)

Married	38.9 (35)	82.9 (68)

Divorced/ Separated	3.3 (3)	4.9 (4)

Widowed	53.3 (48)	11.0 (9)

Number of children M (SD, range)	6.0 (2.76, 1–13)	6.8 (2.63, 2–16)

Years of Schooling M (SD, range)	5.2 (3.48, 0–14)	3.7 (3.28, 0–14)

Highest degree obtained % (n)

No degree	48.9 (44)	61.0 (50)

Primary School	46.7 (42)	35.4 (29)

Secondary School	4.4 (4)	3.6 (3)

Possessions % (n)

House	93.3 (84)	98.8 (81)

Agricultural Field	80.0 (72)	96.3 (79)

Monthly Income M (SD, range)	2922.2 (6849.5, 0–41.000)	3695.1 (6051.6, 0–35.000)

Social Integration

Number of friends M (SD, range)	4.3 (4.0, 0–20)	4.9 (3.7, 0–20)

Community activities % (n)	94.4 (85)	92.7 (76)

Memberships in cooperatives M (SD, range)	.7 (.8, 0–3)	.7 (.9, 0–5)

Family members lost in 1994 M (SD, range)	14 (1.6, 0–70)	3 (.4, 0–24)

Displacement due to genocide % (n)	98.9 (89)	82.9 (68)

Destination of displacement % (n)

Same district	75.5 (68)	15.9 (13)

Other district (Bugesera, Kibuye)	23.3 (21)	59.8 (49)

Foreign country (DRC)	-	7.3 (6)

Years spent in prison M (SD, range)	n.a.	8.5 (4.4, .2-15.7)


	ABFAB	FBC	FPH	Total

Women who stopped breastfeeding before 6 months	n = 65	n = 7	n = 14	n = 86

Stopped bf before mastitis	5	1	2	8

Stopped within 3 wks	29	2	5	36*

Stopped between 3 and 26 wks	31	4	7	42

Women breastfeeding at 6 months	n = 70	n = 19	n = 31	n = 120

Mastitis in previous 3 wks	2	0	0	2

Mastitis > 3 wks earlier	68	19	31	118

Total women with mastitis				206

Women who stopped breastfeeding before 6 months

Stopped bf before mastitis

Stopped within 3 wks

Stopped between 3 and 26 wks

Women breastfeeding at 6 months

Mastitis in previous 3 wks

Mastitis > 3 wks earlier

Total women with mastitis


	Pencil	Oil-pastel	Gouache	F(2,98)

	(M/SD)	(M/SD)	(M/SD)


Protein ID	Orthologs	Potential functions

Wolco1| 166770	STE20	Growth, virulence, and sclerotial formation

Wolco1| 43954	STE11	Growth, virulence, and sclerotial formation

Wolco1| 150169	STE7	Growth, virulence, and sclerotial formation

Wolco1| 75024	MKK2	Regulate MAPK signaling pathway

Wolco1| 144702	PBS2	Regulate MAPK signaling pathway

Wolco1| 135363	BCK1	Regulate MAPK signaling pathway

Wolco1| 121529	CLA4	Pathogenicity, mycelial growth and conidial morphology

Orthologs	Potential functions

STE20	Growth, virulence, and sclerotial formation

STE11	Growth, virulence, and sclerotial formation

STE7	Growth, virulence, and sclerotial formation

MKK2	Regulate MAPK signaling pathway

PBS2	Regulate MAPK signaling pathway

BCK1	Regulate MAPK signaling pathway

CLA4	Pathogenicity, mycelial growth and conidial morphology


Individual subject characteristics	Prognostic factors

	Age	Confirmatory

	Gender	Exploratory

	Height, weight, body mass index	Exploratory

	Ethnicity/race	Exploratory

Lifestyle factors

	Participation in sports activities or physical fitness level	Exploratory

	Smoking	Exploratory

	Alcohol use	Exploratory

Sociodemographic characteristics

	Marital status	Exploratory

	Level of education	Exploratory

	Income	Exploratory

	Employment status	Exploratory

Nature and severity of the low back pain

	Duration of the low back pain	Confirmatory

	Non-specific	Exploratory

	Radiation	Exploratory

	Previous low back pain treatment received	Exploratory

Comorbidities, e.g., diabetes, heart disease

	Presence of comorbidities	Exploratory

Number of comorbidities	Exploratory

Category of comorbidities	Exploratory

 Type of treatment	Manipulation, mobilization, combination

 Psychosocial factors	e.g., Back Depression Inventory, Fear Avoidance Beliefs Questionnaire	Confirmatory

Treatment preference/ expectation	e.g., preference for treatment, previous experience with treatment, expectation to final improvement, self-efficacy scale/beliefs	Confirmatory

Individual subject characteristics	Prognostic factors

	Age

	Gender

	Height, weight, body mass index

	Ethnicity/race

Lifestyle factors

	Participation in sports activities or physical fitness level

	Smoking

	Alcohol use

Sociodemographic characteristics

	Marital status

	Level of education

	Income

	Employment status

Nature and severity of the low back pain

	Duration of the low back pain

	Non-specific

	Radiation

	Previous low back pain treatment received

Comorbidities, e.g., diabetes, heart disease

	Presence of comorbidities

Number of comorbidities

Category of comorbidities

Type of treatment	Manipulation, mobilization, combination

Psychosocial factors	e.g., Back Depression Inventory, Fear Avoidance Beliefs Questionnaire

Treatment preference/ expectation	e.g., preference for treatment, previous experience with treatment, expectation to final improvement, self-efficacy scale/beliefs

Confirmatory

Exploratory

Exploratory

Exploratory

Lifestyle factors

Exploratory

Exploratory

Exploratory

Sociodemographic characteristics

Exploratory

Exploratory

Exploratory

Exploratory

Nature and severity of the low back pain

Confirmatory

Exploratory

Exploratory

Exploratory

Comorbidities, e.g., diabetes, heart disease

Exploratory

Exploratory

Exploratory

Confirmatory

Confirmatory


Systems	Plot area (m2)	Gradient (°)	Aspect	Agro type (by Chinese system)	Bulk density (g cm−3)	pH	OM (g kg−1)	TN (g kg−1)	AN (g kg−1)	TP (g kg−1)	AP (g kg−1)

S1	56	6.3	NE36°	Purple soil	1.26	7.81	29.12	1.38	0.104	0.78	0.022

S2	54	4.7	NE98°	1.31	7.78	25.36	1.44	0.118	0.78	0.015


	B	SE	Significance

(Constant)	−0.57	0.05

City of residence	0.25	0.06	0.000*

Smoker(s) present in the home	0.12	0.07	0.073


Tumor Response as per RECIST v1.1	Arm A, N = 3	Arm B, N = 5

Number of patients	Number of patients

CR	0	0

PR	0	0

SD	1	2

PD	2	3


Number of eligible patients	420	Type of procedure

Primary procedures	196	Aesthetic

n = 378	131	Aesthetic and functional

	51	Functional

Revision procedures	31	Aesthetic

n = 42	9	Aesthetic and functional

	2	Functional


Incubation medium [Fe] (mM)	Measured MR relaxation times	Cell function assays

T1 (ms)	T2 (ms)	Viability (%)	Proliferation (%)

0	2166 ± 135	85.7 ± 9.0	100 ± 14	100 ± 18

0.0036	1263 ± 193	16.1 ± 2.6	96 ± 19	92 ± 8


	No.	%

Gender

 Male	59	54.13

 Female	50	45.87

Chemotherapy

 Gemcitabine alone	41	37.61

 Gemcitabine combined with other drugs*	68	62.39

Primary pancreas tumor

 Head	50	45.87

 Body or tail	35	32.11

 Unknown	24	22.02

Stage of disease

 Locally advanced	10	9.17

 Metastatic	70	64.22

 Unknown	29	26.61

Distant metastasis

 Liver	50	71.43

 Lung	2	2.86

 bone	4	5.71

 Abdomen	5	7.14

	No.	%

		2

Unknown	29	26.61

Distant metastasis

Liver	50	71.43

Lung	2	2.86

bone	4	5.71

Abdomen	5	7.14


Characteristic		Number (n)	Percentage (%)

Gender	Male	155	55

Female	127	45

Gestational age (weeks)	28–36	115	41

≥37–42	168	59

Postnatal age at measurement	≤24 h	9	3

2 days	54	19

3 days	84	30

4 days	73	25

5–10 days	58	21

Characteristic		Number (n)	Percentage (%)

	M		5

Characteristic		Number (n)	Percentage (%)

Gender	ale	155	5

Female	127	45

Gestational age (weeks)	28–36	115	41

≥37–42	168	59

Postnatal age at measurement	≤24 h	9	3

2 days	54	19

3 days	84	30

4 days	73	25

5–10 days	58	21


Ash sample	Fraction	Total	Total independent measurment

Water soluble	Acid soluble/exchangeable	Reducible	Oxidizable	Entrapped in parent matter

A	0.0008	0.004	0.01	0.201	0.359	0.575	0.499

B	0.0007	0.005	0.02	0.159	0.365	0.550	0.520


Variable	Adjusted odds ratio (95% CI)	SE

CGPA	15.27 [6.28, 27.11]∗∗∗	0.88

Age <30 years	0.31 [0.06, 1.63]	0.85

Male gender	1.13 [0.50, 2.55]	0.42

Home residence (ref = rural)

 Semiurban	1.49 [0.41, 5.37]	0.65

 City/urban	1.44 [0.38, 5.42]	0.68

Father highly educated 	0.56 [0.21, 1.49]	0.49

Mother highly education	1.23 [0.55, 2.76]	0.41

Entered nursing with WASSCE 	0.32 [0.04, 2.63]	1.08

Nursing was a first career of choice	0.50 [0.21, 1.19]	0.45

Read science in formal school	1.2 [0.5, 2.6]	0.40

Variable	Adjusted odds ratio (95% CI)	SE

City/urban	1.44 [0.38, 5.42]	0.68

Father highly educated	0.56 [0.21, 1.49]	0.49

Mother highly education	1.23 [0.55, 2.76]	0.41

Entered nursing with WASSCE	0.32 [0.04, 2.63]	1.08

Nursing was a first career of choice	0.50 [0.21, 1.19]	0.45

Read science in formal school	1.2 [0.5, 2.6]	0.40


Gene names	RS	Gene names	RS	Gene names	RS

KRT19	1.6	PTGES2	0.4	BCL7C	0.2

BARD1	1.6	PREX2	0.4	ZNF18	0.2

MST1R	1.5	USP1	0.4	PGLS	0.2

S100A14	1.2	EHF	0.4	CNTN4	0.2

LGALS1	1.2	ADM	0.4	BACH1	0.2

RNF168	1.1	GRM4	0.4	ZFPL1	0.2

TFF1	1	SHFM1	0.4	MAGED2	0.1

SPEN	1	EMP3	0.4	TMEM43	0.1

WDR18	0.9	PTGES	0.3	GALNT5	0.1

RRAS	0.9	TRAF1	0.3	HMX1	0.1

PLEK2	0.8	NAMPT	0.3	RASSF6	0.1

CD248	0.8	BCL2L12	0.3	PFN1	0.1

RHBDL2	0.8	MAML1	0.3	SLC16A7	0.1

CAPN5	0.7	USP24	0.3	ZBTB40	0.1

S100A16	0.7	AMHR2	0.3	MAGED4	0.1

CDC6	0.6	PSMG3	0.3	PIF1	0.1

ENDOG	0.6	NFE2L2	0.3	MBTPS1	0.1

GNG2	0.6	RAPH1	0.3	HDAC4	0.1

CLDN18	0.6	TSHZ2	0.2	VASN	0.1

RNF169	0.5	RNF146	0.2	PSME3	0.1

NR3C1	0.5	NFIL3	0.2	AMN	0.1

TMC8	0.5	SPINK1	0.2	ERCC1	0.1

AKT1S1	0.5	OSTM1	0.2	BRD9	0.1

KLK10	0.5	ESRRG	0.2	B4GALNT1	0.1

SLC2A1	0.5	XRCC3	0.2	PLEKHG5	0.1

ANTXR1	0.4	SLC4A7	0.2	ARHGAP33	0.1

CHSY1	0.4	DPH1	0.2	CYP24A1	0.1

ELAC1	0.4

Gene names	RS	Gene names	RS	Gene names

KRT19	1.6	PTGES2	0.4	BCL7C

BARD1	1.6	PREX2	0.4	ZNF18

MST1R	1.5	USP1	0.4	PGLS

S100A14	1.2	EHF	0.4	CNTN4

LGALS1	1.2	ADM	0.4	BACH1

RNF168	1.1	GRM4	0.4	ZFPL1

TFF1	1	SHFM1	0.4	MAGED2

SPEN	1	EMP3	0.4	TMEM43

WDR18	0.9	PTGES	0.3	GALNT5

RRAS	0.9	TRAF1	0.3	HMX1

PLEK2	0.8	NAMPT	0.3	RASSF6

CD248	0.8	BCL2L12	0.3	PFN1

RHBDL2	0.8	MAML1	0.3	SLC16A7

CAPN5	0.7	USP24	0.3	ZBTB40

S100A16	0.7	AMHR2	0.3	MAGED4

CDC6	0.6	PSMG3	0.3	PIF1

ENDOG	0.6	NFE2L2	0.3	MBTPS1

GNG2	0.6	RAPH1	0.3	HDAC4

CLDN18	0.6	TSHZ2	0.2	VASN

RNF169	0.5	RNF146	0.2	PSME3

NR3C1	0.5	NFIL3	0.2	AMN

TMC8	0.5	SPINK1	0.2	ERCC1

AKT1S1	0.5	OSTM1	0.2	BRD9

KLK10	0.5	ESRRG	0.2	B4GALNT1

SLC2A1	0.5	XRCC3	0.2	PLEKHG5

ANTXR1	0.4	SLC4A7	0.2	ARHGAP33

CHSY1	0.4	DPH1	0.2	CYP24A1

ELAC1	0.4


	SNP-database region

Scan-statistic region	Inter-gene	Within-gene	Regions detected only by scan statistic	Total no. regions

Non-gene scan statistic	33 (8)a	0	72 (12)	105 (20)

Gene scan statistic	10 (7)	38 (17)	87 (20)	135 (44)

Total	43 (15)	38 (17)	159 (32)	240 (64)


Reference	Country	Study design	Sample size	Data source/sample type	Results

[30]	China	The 5th Chinese National Nutrition and Health Survey (2010–2012)	2111	Questionnaire of dietary Mn intake	Men	A decreased risk of MetS with higher Mn intake.

Women	An increased risk of MetS with higher Mn intake.

MetS components	Mn intake was inversely associated with abdominal obesity and hypertriacylglycerolaemia in men, but positively associated with low HDL-cholesterol in both men and women.

[31]	Korea	The Korea National Health and Nutrition Examination Survey (2007–2008)	5136	Questionnaire of dietary Mn intake	Men	No difference

Women/MetS components	The women subjects with high blood pressure showed significantly lower intake of Mn than did control subjects.

[32]	China	Cross-sectional study	Cases: 221 Controls: 329	Questionnaire of dietary Mn intake	Men/women	A lower risk of developing MetS in the second, third, and highest quintiles of Mn intake with respect to the lowest quintile after adjusting age, sex, and energy intake.

MetS components	Daily intake of Mn was decreased with the increasing number of MetS components.

[5]	Poland	Cross-sectional study	313 (men aged 50–75 years)	Serum (Mn level)	Significant positive correlations (Mn–BMI, Mn–abdominal circumference, Mn–waist-to-hip ratio, Mn–insulin, Mn–HOMA-IR), but no correlation with MetS.

[33]	Korea	The Korea National Health and Nutrition Examination Survey (2008)	1405	Whole blood (Mn level)	No difference

Urine (Mn level)	No difference

Reference	Country	Study design	Sample size	Data source/sample type	Results

[30]	China	The 5th Chinese National Nutrition and Health Survey (2010–2012)	2111	Questionnaire of dietary Mn intake	Men

Women

MetS components

[31]	Korea	The Korea National Health and Nutrition Examination Survey (2007–2008)	5136	Questionnaire of dietary Mn intake	Men

Women/MetS components

[32]	China	Cross-sectional study	Cases: 221 Controls: 329	Questionnaire of dietary Mn intake	Men/women

MetS components

[5]	Poland	Cross-sectional study	313 (men aged 50–75 years)	Serum (Mn level)	Significant positive correlations (Mn–BMI, Mn–abdominal circumference, Mn–waist-to-hip ratio, Mn–insulin, Mn–HOMA-IR), but no correlation with MetS.

[33]	Korea	The Korea National Health and Nutrition Examination Survey (2008)	1405	Whole blood (Mn level)	No difference

Urine (Mn level)	No difference

Results

A decreased risk of MetS with higher Mn intake.

An increased risk of MetS with higher Mn intake.

Mn intake was inversely associated with abdominal obesity and hypertriacylglycerolaemia in men, but positively associated with low HDL-cholesterol in both men and women.

No difference

The women subjects with high blood pressure showed significantly lower intake of Mn than did control subjects.

A lower risk of developing MetS in the second, third, and highest quintiles of Mn intake with respect to the lowest quintile after adjusting age, sex, and energy intake.

Daily intake of Mn was decreased with the increasing number of MetS components.

Significant positive correlations (Mn–BMI, Mn–abdominal circumference, Mn–waist-to-hip ratio, Mn–insulin, Mn–HOMA-IR), but no correlation with MetS.

No difference

No difference


Theme	Number of mode-sensitive* items of total number of items	Median (and maximum)odds ratio among mode-sensitive items

Health behaviour

Medicine	0/3	-

Smoking habits	0/1	-

Self assessments

Self-esteem	8/9	1.57 (2.57)

Well-being	9/11	1.55 (2.20)

Depression	3/6	2.12 (2.21)

Stress	12/15	1.67 (2.44)

Theme	Number of mode-sensitive* items of total number of items

Health behaviour

Medicine	0/3

Smoking habits	0/1

Self assessments

Self-esteem	8/9

Well-being	9/11

Depression	3/6

Stress	12/15

Median (and maximum)odds ratio among mode-sensitive items

-

-

1.57 (2.57)

1.55 (2.20)

2.12 (2.21)

1.67 (2.44)


	Total	No education	Primary	Secondary	Some college or more

overall change	−2.75	−3.44	−2.37	−2.22	−0.81


 	Risk of bias	Applicability concerns concerns

First author, year	Patient selection	Index test	Reference standard	Flow and timing	Patient selection	Index test	Reference standard

Beldame, 2011 [23]	?	+	+	-	+	+	+

Boeree, 1991 [24]	-	?	+	+	+	+	+

Decker, 1988 [33]	?	+	?	-	+	+	+

Harilainen, 1987 [25]	+	?	?	-	+	+	+

Katz, 1986 [26]	-	+	?	+	+	+	+

Lee, 1988 [27]	-	+	?	-	+	+	+

Lucie, 1984 [28]	-	+	?	-	+	+	+

Mulligan, 2011 [29]	+	+	?	?	+	+	+

Noyes, 1980 [30]	-	?	+	-	?	+	+

Richter, 1996 [34]	-	+	?	+	+	+	+

Schwartz, 1997 [35]	-	+	+	+	+	+	+

Tonino, 1986 [31]	-	+	?	?	+	+	+

Wagemakers, 2010 [19]	+	+	+	+	+	+	+

Wong, 1999 [32]	+	?	?	+	+	+	+

	Risk of bias	Applicability concerns concerns

First author, year	Patient selection	Index test	Reference standard	Flow and timing	Patient selection	Index test

Beldame, 2011 [23]	?	+	+	-	+	+

Boeree, 1991 [24]	-	?	+	+	+	+

Decker, 1988 [33]	?	+	?	-	+	+

Harilainen, 1987 [25]	+	?	?	-	+	+

Katz, 1986 [26]	-	+	?	+	+	+

Lee, 1988 [27]	-	+	?	-	+	+

Lucie, 1984 [28]	-	+	?	-	+	+

Mulligan, 2011 [29]	+	+	?	?	+	+

Noyes, 1980 [30]	-	?	+	-	?	+

Richter, 1996 [34]	-	+	?	+	+	+

Schwartz, 1997 [35]	-	+	+	+	+	+

Tonino, 1986 [31]	-	+	?	?	+	+

Wagemakers, 2010 [19]	+	+	+	+	+	+

Wong, 1999 [32]	+	?	?	+	+	+

Applicability concerns concerns

Reference standard

+

+

+

+

+

+

+

+

+

+

+

+

+

+


Tumor stage	N	(%)

Non-invasive carcinoma	24	8.7

Invasive carcinoma

T1	176	61.9

T2	63	22.1

T3	9	3.0

T4	8	3.0

Unknown	4	1.3

Nodal status

N0	187	65.8

≥N1	93	32.7

Unknown	4	1.5

Metastases/recurrence	29	10.4

Treatment

Surgery

BET	224	78.9

Mastectomy	55	19.4

No surgery	5	1.7

SN biopsy	128	45.2

Axillary lymph node dissection	117	41.5

Chemotherapy

Neoadjuvant	24	8.4

Adjuvant	122	42.8

Irradiation	233	81.9

Hormonal therapy	218	76.9

Relationship

Single	16	5.7

Married/living with partner	172	60.5

Divorced/widowed	79	27.8

Unknown	17	6

Education

Compulsory	121	42.2

Post-compulsory	149	52.8

University level	14	5.0

Employment

Employed	77	27.1

Retired	86	30.3

Homemaker/unemployed	88	31.0

Unknown	33	11.6

Tumor stage	N	(%)

Invasive carcinoma

T1	176	61.9

T2	63	22.1

T3	9	3.0

T4	8	3.0

Unknown	4	1.3

Nodal status

N0	187	65.8

≥N1	93	32.7

Unknown	4	1.5

Metastases/recurrence	29	10.4

Treatment

Surgery

BET	224	78.9

Mastectomy	55	19.4

No surgery	5	1.7

SN biopsy	128	45.2

Axillary lymph node dissection	117	41.5

Chemotherapy

Neoadjuvant	24	8.4

Adjuvant	122	42.8

Irradiation	233	81.9

Hormonal therapy	218	76.9

Relationship

Single	16	5.7

Married/living with partner	172	60.5

Divorced/widowed	79	27.8

Unknown	17	6

Education

Compulsory	121	42.2

Post-compulsory	149	52.8

University level	14	5.0

Employment

Employed	77	27.1

Retired	86	30.3

Homemaker/unemployed	88	31.0

Unknown	33	11.6


Primers	5′–3′ sequence (bp)

Primers for 3′-RACE PCR

Kiss1-F	CGCCACAAGCGGCCAAGAAG

Kiss2-F	AGGGCCACATTTCCTGCCGACT

Primers for 5′-RACE PCR

Kiss1-R	CCCGCTTCTTGGCCGCTTGT

Kiss2-R	CCGAACGGATTGCGGTTGAATTTG

Primers for qPCR

Kiss1-F	GGTCTCTTAGGTACACCCCGT	This study

Kiss1-R	ACAGCTCCTCGCTCATTTG

Kiss2-F	ACGGACGACTCAGGTTCTCT	This study

Kiss2-R	GCCCTCGATTTCACTGTCTT

actin-F	AGTATTTGCGCTCGGGTG	Aroua et al. (27)

actin-R	CAGCCTTCCTTCCTGGGT

lhβ-F	TCACCTCCTTGTTTCTGCTG	Aroua et al. (27)

lhβ-R	TAGCTTGGGTCCTTGGTGATG

fshβ-F	TCTCGCCAACATCTCCATC	Aroua et al. (27)

fshβ-R	AGAATCCTGGGTGAAGCACA

gnrh-r1a-F	TGGTCATGAGTTGCTGCTACA	Penaranda et al. (25)

gnrh-r1a-R	AGACACCCCTCTCCGTCTTT

gnrh-r1b-F	TCGTCACGCTCTACGTTGTC	Penaranda et al. (25)

gnrh-r1b-R	AGGCAGGACTCTCCACCTTT

gnrh-r2-F	TCACCTTCTCCTGCCTCTTC	Penaranda et al. (25)

gnrh-r2-R	TTGGAAGATGCCTTCCCTTT

Primers	5′–3′ sequence (bp)

gnrh-r2-R	TTGGAAGATGCCTTCCCTTT


Accession ID	Amplicon Size	Primers used

α ENaC-wt	325 bp	Sense: 5'-TCATGCTGCTACGCCGGTTCC-3'

		Antisense:5'-TCCATCAGTTTACAAGGGAG-3'

α ENaC a	266 bp	Sense: 5'-CAGAGCTCCTGGGGGCGCCTT-3'

		Antisense: 5'-TCCTTCTGTCACGATGGTCA-3'

α ENaC-b	278 bp	Sense: 5'-GGATGATGGTGGCTTCAACT-3'

		Antisense: 5'-ACACCCAGGAGCTCTGCTTT-3'

α ENaC-c	59 bp	Sense: 5'-GCTCCTGGGTGTGATCAACTA-3'

		Antisense: 5'-AAAGAAGGTGGTGGGGATGT-3'

	59 bp	Sense: 5'-GGATGATGGTGGCTTCAACT-3'

		Antisense: 5'-AAAGAAGGTGGTGGGGATGT-3'

α ENaC-d	99 bp	Sense: 5'-CCACGCGTCCGAAGAAAC-3'

		Antisense:5'-AAAGAAGGTGGTGGGGATGT-3'

	99 bp	Sense: 5'-CCACGCGTCCGAAGAAACTG-3'

		Antisense:5'-TAAAGAAGGTGGTGGGGATG-5'

CK479583	767 bp	Sense: 5'-GCCCCAGCAGGGCATGACCC-3'

		Antisense: 5'-CTAGAGTAGCATAGGCAGGT-3'

CK475461	814 bp	Sense: 5'-TCCAAGTATACACAGCAGGT-3'

		Antisense: 5'-TACAGGAGTCAGGCTGTGAG-3'

CK364785	764 bp	Sense: 5'-GGGGCTATTGCTATTATAAA-3'

		Antisense:5'-CCACACAGAGGGCTCGGCGGG-3'

CK475819	748 bp	Sense: 5'-GATTCCCGGGATCTTGGA-3'

		Antisense: 5'-AGGCTGACCATCGTGACAG-3'

CB690980	376 bp	Sense: 5'-CCACGCGTCCGAAGAAAC-3'

		Antisense: 5'-AAAGAAGGTGGTGGGGATGT-3'

Pgk	263 bp	Sense: 5'-GCTGCAGAACTCAAATCTCT-3'

		Antisense:5'-TGTGTGCAGTCCCAAAAGCA-3'


Powders Prepared with Different Process Control Agents	Crystallite Size (nm)	Lattice Constant (Å)	Strain (%)

None	11.8	3.1636	0.688

Ethanol	24.2	3.1549	0.483

Stearic acid	14.7	3.1648	0.590

Powders Prepared with Different Process Control Agents	Crystallite Size (nm)	Lattice Constant (Å)	Strain (%)

Stearic acid	14.7	3.1648	0.590


Region	States	Frequency	IAQ Practice Indexb	Schools with index ≥ 70 (%)

1	Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont	25	71.8	64

2	New Jersey, New York, Puerto Rico,c U.S. Virgin Islandsc	28	71.9	57

3	Delaware, Maryland, Pennsylvania, Virginia, West Virginia, District of Columbia	21	77.0	71

4	Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee	46	64.4	41

5	Illinois, Indiana, Michigan, Minnesota, Ohio, Wisconsin	87	73.0	60

6	Arkansas, Louisiana, New Mexico, Oklahoma, Texas	40	70.7	60

7	Iowa, Kansas, Missouri, Nebraska	15	66.7	53

8	Colorado, Montana, North Dakota, South Dakota, Utah, Wyoming	13	66.3	54

9	Arizona, California, Hawaii, Nevada, Pacific Islands,c Tribal Nations subject to U.S. law	27	70.1	56

10	Alaska, Idaho, Oregon, Washington	16	77.1	81

Region	States	Frequency	IAQ Practice Indexb	Schools with index ≥ 70 (%)

1	Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont	25	71.8	64

2	New Jersey, New York, Puerto Rico,c U.S. Virgin Islandsc	28	71.9	57

3	Delaware, Maryland, Pennsylvania, Virginia, West Virginia, District of Columbia	21	77.0	71

4	Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee	46	64.4	41

5	Illinois, Indiana, Michigan, Minnesota, Ohio, Wisconsin	87	73.0	60

6	Arkansas, Louisiana, New Mexico, Oklahoma, Texas	40	70.7	60

	Iowa, Kan	1	66.	5

Region	States	Frequency	IAQ Practice Indexb	Schools with index ≥ 70 (%)

7	sas, Missouri, Nebraska	5	7	3

8	Colorado, Montana, North Dakota, South Dakota, Utah, Wyoming	13	66.3	54

9	Arizona, California, Hawaii, Nevada, Pacific Islands,c Tribal Nations subject to U.S. law	27	70.1	56

10	Alaska, Idaho, Oregon, Washington	16	77.1	81


Zone	2008 NBS* Est. U5sfrom 2002 Census	U5s Registered	LLINs delivered†	LLINS issued‡ (%)	U5s not receiving an LLIN**

Tanga	288,185	N/A††	402,448	380,458(94.5)	0‡‡


County	Pre-treatment	Post-treatment

Number of schools	Number of children	Number of schools	Number of children

Bomet	1	108	1	103

Bungoma	1	108	1	105

Busia	2	214	2	210

Homa Bay	1	108	1	102

Kakamega	2	212	2	213

Kisii	1	105	1	103

Kisumu	3	312	3	313

Kwale	3	317	3	316

Mombasa	1	98	1	108

Narok	2	215	2	214

Taita Taveta	1	102	1	91

Overall	18	1899	18	1878


	Patient 1	Patient 2	Patient 3

Origin	Dominican Republic	Haiti	Haiti

Age (years)	25	52	41

Sex (W/M)	W	W	M

Date of diagnosis (and onset of symptoms)	December 2014	January 2015	December 2014

Time in Guadeloupe	1 year	10 years	Several years

Initial symptoms	Generalized seizure	Generalized seizure	Ischemic stroke and tonic-clonic seizuresa

Number of colloidal cysts	1	5	0

Number of vesicular cysts	1	1	0

Number of calcified cerebral cysts	3	9	30

T. solium antibodies in serum (ELISA)	Negative	Negative	Negative

T. solium antibodies in CSF (EITB)	Negative	Positive	Not done

Screening for taeniasis in index case	Negative	Negative	Negative

Screening for taeniasis in household	Negative	Negative	Negative

Treatment	Albendazole + Steroids + Valproic acid	Albendazole + Praziquantel + Steroids + Levetiracetam	Surgical removala + Albendazole + Steroids + Valproic acid

Seizure recurrence in the first 6 months after treatment	Several	Multiple episodes in the first months after tapering steroids	No recurrence


Domain	APH	PPH	Eclampsia

Initial assessment & diagnosis	Per vaginum examination (34%)	Exploring the uterus for blood clots (39%)	Weight (4%)

Swelling on body parts related to severe anemia (8%), blurred vision related to night blindness (1%)

Diagnosed eclampsia as pre eclampsia or pregnancy induced hypertension (26%)

First line management	Antibiotic (12%)	Alternate drugs mentioned:	Diazepam (5%)

Ergometrine (34%)

Iron folic acid (11%)	Misoprostol (15%)	Diazepam with MgSO4 (3%)

Misoprostol and ergometrine (<1%)	Unindicated drugs mentioned:	Antibiotics (5%)

Injection Tranexamic acid (1%),	Anti hypertensive (6%)

Antibiotics (21%)

Ironfolicacid (11%) Calcium and multivitamin (9%)

Vaginal packing (1%)

Advice	Dietary advice and regular ANC (12%)	Dietary advice and regular ANC (20%)	Regular ANC (3% )

 	Perceived APH is caused by sexual activity or lifting weight; hence advised bed rest	New born care, Early breast feeding

 	 	And Family planning (1%)

Domain	APH	PPH	Eclampsia

Initial assessment & diagnosis	Per vaginum examination (34%)	Exploring the uterus for blood clots (39%)	Swelling on body parts related to severe anemia (8%), blurred vision related to night blindness (1%)

Diagnosed eclampsia as pre eclampsia or pregnancy induced hypertension (26%)

First line management	Antibiotic (12%)	Alternate drugs mentioned:	Diazepam (5%)

Ergometrine (34%)

Iron folic acid (11%)	Misoprostol (15%)	Diazepam with MgSO4 (3%)

Misoprostol and ergometrine (<1%)	Unindicated drugs mentioned:	Antibiotics (5%)

Injection Tranexamic acid (1%),	Anti hypertensive (6%)

Antibiotics (21%)

Ironfolicacid (11%) Calcium and multivitamin (9%)

Vaginal packing (1%)

Advice	Dietary advice and regular ANC (12%)	Dietary advice and regular ANC (20%)	Regular ANC (3% )

	Perceived APH is caused by sexual activity or lifting weight; hence advised bed rest	New born care, Early breast feeding

		And Family planning (1%)


Pt nr.	Max IAP	Macroscopy	Microscopy	Outcome

1	22	Autopsy findings: Focal ischemia on serosal and mucosal side of small bowel	Mucosa of jejunum and colon almost completely disappeared	Died 2 days after admission to the ICU

7	24	Full necrosis of the sigmoid	Transmural ischemic necrosis sigmoid	Died 67 days after decompression due to bleeding complications caused by pancreatitis

8	26	Dubious signs of ischemia of terminal ileum	Segmental chronic and acute inflammation with perforation; concordant with ischemic enteritis	Died 40 days after decompression due to sepsis and MOF

9	27	Firm necrosis of the jejunum	Severe transmural ischemic enteritis	Discharge to ward 134 days after decompression

10	27	Only necrotic remains of the sigmoid colon	Transmural necrosis	Died 13 days after decompression due to sepsis and MOF

11	29	Full black necrosis of small and large intestine	Not available	Died several hours after decompression, after withdrawal of treatment

12	32	Marbled aspect of left liver lobe	Not available	Died 47 days after decompression, due to sepsis and MOF

13	32	Patchy and full ischemia of the terminal ileum; full ischemia of cecum and left colon	ischemia ileum, cecum and left colon	Discharge to ward 16 days after decompression

Pt nr.	Max IAP	Macroscopy	Microscopy	Outcome

13	32	Patchy and full ischemia of the terminal ileum; full ischemia of cecum and left colon	ischemia ileum, cecum and left colon	Discharge to ward 16 days after decompression


Parameters	Score

Acuteness of the first cry	Absent	0

Present	2

Burst rhythmicity	Absent	0

Present	2

Constancy of the crying intensity	Absent	0

Intermediate	1

Constant	2

Parameters

Acuteness of the first cry

Burst rhythmicity

Constancy of the crying intensity

Score

Absent	0

Present	2

Absent	0

Present	2

Absent	0

Intermediate	1

Constant	2


	Part 1 (n = 104)	Part 2 (n = 56)

Breed [number (%) of cats]

Domestic shorthair cat	85 (81.6)	46 (82.1)

Maine coon	6 (5.7)	3 (5.4)

Norwegian	4 (3.8)	3 (5.4)

Oriental	3 (2.9)	2 (3.6)

Chartreux	2 (2.8)	1 (1.8)

Birman	1 (0.9)	1 (1.8)

Siamese	1 (0.9)	–

Turkish Angora Cat	1 (0.9)	–

British Shorthair	1 (0.9)	–

Gender [number (%) of cats]

Sexually intact female	–	–

Spayed female	40 (38.8)	21 (37.5)

Sexually intact male	4 (3.8)	4 (7.1)

Castrated male	60 (57.6)	31 (55.4)

Age (in years)

Mean age ± SD	7.26 ± 4.0	7.47 ± 4.3

Viral status [number (%) of cats]

Tested for feline immunodeficiency virus (FIV)	89/104 (85.4)	49/56 (87.5)

 FIV positive	12/89 (13.5)	6/49 (12.2)

 Feline leukemia virus positive	0/89 (0)	0/49 (0)

Tested for FHV	80/104 (76.8)	43/56 (76.8)

 FHV positive	14/80 (17.5)	7/43 (16.3)

	Part 1 (n = 104)	Part 2 (n = 56)

Siamese	1 (0.9)	–

Turkish Angora Cat	1 (0.9)	–

British Shorthair	1 (0.9)	–

Gender [number (%) of cats]

Sexually intact female	–	–

Spayed female	40 (38.8)	21 (37.5)

Sexually intact male	4 (3.8)	4 (7.1)

Castrated male	60 (57.6)	31 (55.4)

Age (in years)

Mean age ± SD	7.26 ± 4.0	7.47 ± 4.3

Viral status [number (%) of cats]

Tested for feline immunodeficiency virus (FIV)	89/104 (85.4)	49/56 (87.5)

FIV positive	12/89 (13.5)	6/49 (12.2)

Feline leukemia virus positive	0/89 (0)	0/49 (0)

Tested for FHV	80/104 (76.8)	43/56 (76.8)

FHV positive	14/80 (17.5)	7/43 (16.3)


Feeding Practices	Age of Introduction of Complementary Foods

<17 Weeks n (%)	≥17 Weeks n (%)

Total	395 (62.5)	237 (37.5)

Explanations given for introducing solid foods

 Baby hungry	203 (51.4)	118 (49.8)

 Baby old enough	105 (26.6)	56 (23.6)

 Poor baby weight gain	50 (12.7)	35 (14.8)

 Maternal illness	23 (5.8)	22 (9.3)

 Other reason	14 (3.5)	6 (2.5)

Type of food infant was initially given:

 Baby cereal	244 (61.7)	145 (61.2)

 Pureed or mashed fruit or vegetables	77 (19.5)	36 (15.2)

 Pureed or mashed meat or fish	33 (8.4)	12 (5.1)

 Baby food manufacturers	27 (6.8)	25 (10.5)

 Yoghurt	5 (1.3)	11 (4.6)

 Other food type	9 (2.3)	8 (3.4)

Was it difficult to introduce solid foods?

 Yes	298 (75.4)	115 (48.5)

 No	97 (24.6)	122 (51.5)

Explanations given for difficulty in introducing solid foods

 Mother uncertain about weaning	34 (8.6)	29 (12.2)

 Infant would only accept certain solids and not others	145 (36.7)	112 (47.3)

 Infant preferred drinks to food	166 (42.0)	87 (36.7)

 Infant experienced choking or vomiting	37 (9.3)	4 (1.7)

 Other reason	13 (3.4)	5 (2.1)

Infant took ≥30 min to finish a meal?

 Yes	144 (36.5)	56 (23.6)

 No	251 (63.5)	181 (76.4)

Meals a day

 1	168 (42.5)	35 (14.8)

 2	147 (37.2)	138 (58.2)

 3 or more	80 (20.3)	64 (27.0)

Was salt added to the infant’s solid food?

 Yes	123 (31.1)	143 (60.3)

 No	272 (68.9)	94 (39.7)

Was sugar added to the infant’s solid food?

 Yes	87 (22.0)	79 (33.3)

 No	308 (78.0)	158 (66.7)

Which foods did mothers avoid giving to their infants?

 Any poultry, seafood or other meat	227 (57.5)	76 (32.1)

 Eggs or other dairy products	104 (26.3)	37 (15.6)

 Vegetables (salad)	387 (98.0)	188 (79.3)

 Fruit (fresh)	338 (85.6)	201 (84.8)

 Nuts	395 (100.0)	237 (100.0)

 Honey	387 (98.0)	189 (79.7)

 Processed foods	312 (79.0)	175 (73.8)

 Chocolate or other sweets	277 (70.1)	107 (45.1)

 High salt content foods	86 (21.8)	56 (23.6)

 High sugar content foods	157 (39.7)	98 (41.4)

 High fat content foods	203 (51.4)	186 (78.5)

 Other foods	47 (11.9)	36 (15.2)

Explanations given for not giving particular foods

 The infant dislikes them	127 (32.2)	112 (47.3)

 Heath reasons (allergies/adverse reactions)	91 (23.0)	23 (9.7)

 Food was not cooked at home	47 (11.9)	41 (17.3)

 Concern about choking	89 (22.5)	33 (13.9)

 Infant is still too young	25 (6.3)	19 (8.0)

 Other reason	16 (4.1)	9 (3.8)

Feeding Practices	Age of Introduction of Complementary Foods

<17 Weeks n (%)	≥17 Weeks n (%)

Baby food manufacturers	27 (6.8)	25 (10.5)

Yoghurt	5 (1.3)	11 (4.6)

Other food type	9 (2.3)	8 (3.4)

Was it difficult to introduce solid foods?

Yes	298 (75.4)	115 (48.5)

No	97 (24.6)	122 (51.5)

Explanations given for difficulty in introducing solid foods

Mother uncertain about weaning	34 (8.6)	29 (12.2)

Infant would only accept certain solids and not others	145 (36.7)	112 (47.3)

Infant preferred drinks to food	166 (42.0)	87 (36.7)

Infant experienced choking or vomiting	37 (9.3)	4 (1.7)

Other reason	13 (3.4)	5 (2.1)

Infant took ≥30 min to finish a meal?

Yes	144 (36.5)	56 (23.6)

No	251 (63.5)	181 (76.4)

Meals a day

1	168 (42.5)	35 (14.8)

2	147 (37.2)	138 (58.2)

3 or more	80 (20.3)	64 (27.0)

Was salt added to the infant’s solid food?

Yes	123 (31.1)	143 (60.3)

No	272 (68.9)	94 (39.7)

Was sugar added to the infant’s solid food?

Yes	87 (22.0)	79 (33.3)

No	308 (78.0)	158 (66.7)

Which foods did mothers avoid giving to their infants?

Any poultry, seafood or other meat	227 (57.5)	76 (32.1)

Eggs or other dairy products	104 (26.3)	37 (15.6)

Vegetables (salad)	387 (98.0)	188 (79.3)

Fruit (fresh)	338 (85.6)	201 (84.8)

Nuts	395 (100.0)	237 (100.0)

Honey	387 (98.0)	189 (79.7)

Processed foods	312 (79.0)	175 (73.8)

Chocolate or other sweets	277 (70.1)	107 (45.1)

High salt content foods	86 (21.8)	56 (23.6)

High sugar content foods	157 (39.7)	98 (41.4)

High fat content foods	203 (51.4)	186 (78.5)

Other foods	47 (11.9)	36 (15.2)

Explanations given for not giving particular foods

The infant dislikes them	127 (32.2)	112 (47.3)

Heath reasons (allergies/adverse reactions)	91 (23.0)	23 (9.7)

Food was not cooked at home	47 (11.9)	41 (17.3)

Concern about choking	89 (22.5)	33 (13.9)

Infant is still too young	25 (6.3)	19 (8.0)

Other reason	16 (4.1)	9 (3.8)


	Positive keywords	Negative keywords

BTE	mould, be34, map, gp, 92, audio, inf, be52, ref, staff, reqd, be36, contact	fta, reshel, appt, it, nn, nfa, 2001, rev, lacquer, hn, km, imp, review, 2000

ITE	fta, reshel, appt, it, nn, nfa, 2001, rev, lacquer, hn, km, imp, review, 2000, nh, vent, progress, aid, dt, taken	mould, be34, map, gp, 92, audio, inf, be52, ref, staff, reqd, be36, contact, tri, n, order

	Positive keywords	Negative keywords

BTE	mould, be34, map, gp, 92, audio, inf, be52, ref, staff, reqd, be36, contact	fta, reshel, appt, it, nn, nfa, 2001, rev, lacquer, hn, km, imp, review, 2000

IT	fta, reshel, appt, it,	mould, be34, map, gp, 92, audio, inf, be52, ref, staff, reqd, be3

E	 nn, nfa, 2001, rev, lacquer, hn, km, imp, review, 2000, nh, vent, progress, aid, dt, taken	6, contact, tri, n, order


A. Regions from first iteration analyses

Degree of damage to each ROI	Analysis with Fuzzy images	Analysis with Binary images

Group	Temporal ROI	Frontal ROI	n	Impaired	Not impaired	n	Impaired	Not impaired

Frontal (1)	≤ 25%	≥ 75%	68	18	50	77	19	58

Temporal (2)	≥ 75%	≤ 25%	23	10	13	25	11	14

Both (3)	≥ 75%	≥ 75%	71	48	23	63	45	18

Partial (4)	74%−26%	74%−26%	70	13	57	50	13	37

Neither (5)	≤ 25%	≤ 25%	127	9	118	144	10	134

B. Regions from second iteration analyses

	Analysis with Fuzzy images	Analysis with Binary images

Degree of damage of Putamen ROI	n	Impaired	Not Impaired	n	Impaired	Not Impaired

Putamen damaged (> 25%)	13	3	10	26	5	21

Putamen preserved (≤ 25%)	114	6	108	118	5	113


	+	−

NEURAL ACTIVITY

Spontaneous activity

 Electro-physiology	Basta and Ernst (90), Jastreboff and Sasaki (87), and Manabe et al. (91)	Ma et al. (92)

 Metabolicmarkers	Paul et al. (93)	Wallhausser-Franke et al. (94)

Burst firing	Chen and Jastreboff (88)

Auditory-evoked activity	Ma et al. (92) and Sun et al. (95)

NEUROTRANSMISSION

Excitation

 NMDA	Hu et al. (96) and Hwang et al. (97, 98)

Inhibition

 GABAA	Bauer et al. (99) (GABAA affinity)	Bauer et al. (99) (GABAA binding sites) and Zou and Shang (100)

 GAD65	Bauer et al. (99)

 GAD67		Zou and Shang (100)

 GlyR		Lu et al. (102)

 Serotonin	Liu et al. (101)	Wang et al. (103)

GENE EXPRESSION

 Arg3.1/arc		Hu et al. (96)

 Egr-1		Hu et al. (96)

 c-FOS	Wu et al. (104)	Mahlke and Wallhausser-Franke (105)

INFLAMMATORY MARKERS

 COX-2		Hwang et al. (97)

 IL1β	Hwang et al. (98, 106)

 TNFα	Hwang et al. (98, 106)

	+	−

taneous activity

Electro-physiology	Basta and Ernst (90), Jastreboff and Sasaki (87), and Manabe et al. (91)	Ma et al. (92)

Metabolicmarkers	Paul et al. (93)	Wallhausser-Franke et al. (94)

Burst firing	Chen and Jastreboff (88)

Auditory-evoked activity	Ma et al. (92) and Sun et al. (95)

NEUROTRANSMISSION

Excitation

NMDA	Hu et al. (96) and Hwang et al. (97, 98)

Inhibition

GABAA	Bauer et al. (99) (GABAA affinity)	Bauer et al. (99) (GABAA binding sites) and Zou and Shang (100)

GAD65	Bauer et al. (99)

GAD67		Zou and Shang (100)

GlyR		Lu et al. (102)

Serotonin	Liu et al. (101)	Wang et al. (103)

GENE EXPRESSION

Arg3.1/arc		Hu et al. (96)

Egr-1		Hu et al. (96)

c-FOS	Wu et al. (104)	Mahlke and Wallhausser-Franke (105)

INFLAMMATORY MARKERS

COX-2		Hwang et al. (97)

IL1β	Hwang et al. (98, 106)

TNFα	Hwang et al. (98, 106)


	N = 134	(%)

Food reactions

Gastro-intestinal symptoms	67	(50)

OAS – Oral Allergy Syndrome	63	(47)

Difficulty breathing	53	(40)

Skin symptoms	50	(37)

Anaphylaxis	20	(15)

Eye-nose symptoms	19	(14)

Food reactions during the last 12 months	60	(45)

Allergic diseases	100	(75)

Rhino conjunctivitis	69	(52)

Eczema	64	(48)

Asthma	44	(33)

Additional allergy/hypersensitivity	95	(71)

Additional family member with food hypersensitivity	78	(58)

Parent(s)	49	(37)

Sibling(s)	45	(34)

	N = 134	(%)

Food reactions

Gastro-intestinal symptoms	67	(50)

OAS – Oral Allergy Syndrome	63	(47)

Difficulty breathing	53	(40)

Skin symptoms	50	(37)

Anaphylaxis	20	(15)

Eye-nose symptoms		(1

	19	4)

Food reactions during the last 12 months	60	(45)

Allergic diseases	100	(75)

Rhino conjunctivitis	69	(52)

Eczema	64	(48)

Asthma	44	(33)

Additional allergy/hypersensitivity	95	(71)

Additional family member with food hypersensitivity	78	(58)

Parent(s)	49	(37)

Sibling(s)	45	(34)


	Number of airlines

Pre-boarding arrangements

• Request a food “buffer zone”	5

• No “buffer zone”	3

• Request “allergen-free meal”	1

• Pre-boarding to wipe down seats and table trays	Yes 4

No 1

• Buffer zone for fragrance sensitivity	2

• Announcements to inform customers there is a peanut or tree-nut allergic passenger on board or that peanut products will not be served	Yes 4

No 7

Free snack policy on peanut/nut/sesame

• Serving peanuts	Yes 2

No 11

• Serving nuts and sesameaw	Yes 8

No 1

• First class warmed nuts	3

Gluten-free meals	Yes 11

No 1

Lactose-free meals	1

Shellfish served	Yes 4

No 3

Fish served	Yes 6

No 1

Buffer zones for passengers allergic to pets	5

• Announcements to inform customers there is a peanut or tree-nut allergic passenger on board or that peanut products will not be served	No 7

Free snack policy on peanut/nut/sesame

• Serving peanuts	Yes 2

No 11

• Serving nuts and sesameaw	Yes 8

No 1

• First class warmed nuts	3

Gluten-free meals	Yes 11

No 1

Lactose-free meals	1

Shellfish served	Yes 4

No 3

Fish served	Yes 6

No 1

Buffer zones for passengers allergic to pets	5


Risk category	Criteria	Age to commence screening	Screening Test	Screening frequency (years)

Average-risk(Age-only)	Age 50–74 years	50	FOBT	2

Sigmoidoscopy	5

Colonoscopy	10

Moderate-risk(FamilyHx)	Family history of CRC in 1 first-degree relative ≥60 years	40	FOBT	2

Sigmoidoscopy	5

Colonoscopy	10

	Family history of CRC in 1 first-degree relative < 60 years	40b	Colonoscopy	5

Family history of CRC in 2 or more relatives

High-risk (PersonalHx)	Personal history of a bowel conditionc	40d	Colonoscopy	5

Highest-risk (Family/PersonalHx)	Personal history of a bowel condition and family history of CRC

Moderate-risk(FamilyHx)	Family history of CRC in 1 first-degree relative ≥60 years	40	Colonoscopy	10

	Family history of CRC in 1 first-degree relative < 60 years	40b	Colonoscopy	5

Family history of CRC in 2 or more relatives

High-risk (PersonalHx)	Personal history of a bowel conditionc	40d	Colonoscopy	5

Highest-risk (Family/PersonalHx)	Personal history of a bowel condition and family history of CRC


Targeted Gene	Primer	Sequence (5′–3′)

ALDOA	Forward	ATGCCCTACCAATATCCAGC

Reverse	GACAGCCCATCCAACCCT

CDC20	Forward	GGCACCAGTGATCGACACATTCGCAT

Reverse	GCCATAGCCTCAGGGTCTCATCTGCT

CCNB2	Forward	GCGTTGGCATTATGGATCG

Reverse	TCTTCCGGGAAACTGGCTG

CDC45	Forward	TGGACTGCACACGGATCT

Reverse	AACCTGGCTGCGGTATAG

TK1	Forward	TGGCTGTCATAGGCATCGAC

Reverse	CCAGTGCAGCCACAATTACG

β-Actin	Forward	AGCGAGCATCCCCCAAAGTT

Reverse	GGGCACGAAGGCTCATCATT

Targeted Gene	Primer	Sequence (5′–3′)

ALDO	Forward	ATGCCCTACCAATATCCAGC

Revers	GACAGCCCATCCAAC

A	e	CCT

CDC20	Forward	GGCACCAGTGATCGACACATTCGCAT

Reverse	GCCATAGCCTCAGGGTCTCATCTGCT

CCNB2	Forward	GCGTTGGCATTATGGATCG

Reverse	TCTTCCGGGAAACTGGCTG

CDC45	Forward	TGGACTGCACACGGATCT

Reverse	AACCTGGCTGCGGTATAG

TK1	Forward	TGGCTGTCATAGGCATCGAC

Reverse	CCAGTGCAGCCACAATTACG

β-Actin	Forward	AGCGAGCATCCCCCAAAGTT

Reverse	GGGCACGAAGGCTCATCATT


Resistance pattern to the NARMS antimicrobial panel	% of isolates with resistance profile (no.)	Plasmid profile groups detected (no.)a	Species of isolates with plasmids (no.)	PFGE patterns

STR, FIS, TET, SXT	33% (14)	II, X(3), VIII	S. sonnei (4), S. flexneri	III, V, VI, IX, X

AMP, STR, FIS, TET, SXT	14% (6)	II(4), VI	S. sonnei (5)	I, IV, VII, VIII, XI, XII

AMP, CHL, STR, FIS, TET	10% (4)	none	none

AMP, CHL, TET	7% (3)	VII	S. flexneri 3a	XX, XXIII, XV

AMP, CHL, STR, FIS, TET, SXT	7% (3)	IV(2), V	S. flexneri 3a (2), S. sonnei

TET	5% (2)	I, IV	S. flexneri 1b (2)	XIX

AMP, CHL, FIS, TET	5% (2)	IV(2)	S. flexneri 2a (2)	XVII

CHL, STR, FIS, TET, SXT	5% (2)	V(2)	S. flexneri 1c (2)	XV

AMP, CHL, FIS, TET, SXT	2% (1)	IV	S. flexneri 2a	XVIII

AMP, KAN, STR, FIS	2% (1)	IV	S. sonnei	XIII

CHL, FIS, TET, SXT	2% (1)	III	S. flexneri Y var.	XXIV

AMP, CHL, STR, TET	2% (1)	IX	S. flexneri 1b	XIV

AMP, STR, FIS, SXT	2% (1)	IX	S. sonnei

AMC, AMP, GEN, STR, FIS	2% (1)	IV	S. flexneri


	Putative fox feces	Locations

	Number of samples	Positive samples (%)	Number of locations	Positive locations (%)

Anatolia	186	7 (3.8)	59	3 (5.1)

Thrace	219	1 (0.5)	114	1 (0.9)

Total	405	8 (1.9)	173	4 (2.3)


Characteristics	No. of patients	Expression of CIP2A	Pvalue

		Low, n (%)	High, n (%)

Distant metastasis

Yes	63	11 (11)	52 (28)	<0.01

No	217	85 (89)	132 (72)

Death

Yes	67	14 (15)	53 (29)	0.01

No	213	82 (85)	131 (71)


	Early differentiation	Intermediate differentiation	Terminal differentiation

Phenotypic markers

CD28	++	+/−	–

CD27	++	+/−	–

CD45RA	++	+/−	+/−

CCR7	++	+	–

CD62L	++	+	–

CD57	–	+/−	++

KLRG1	–	+/−	++

Other NKR (KIR, NKG2, and CD56)	–	+/−	++

Functional features

Proliferation	++	+	–

Telomerase activity	++	+	–

Telomeres	+++	++	+

Cytotoxicity	–	+	++

Cytokine secretion (TNF-α, IFN-γ)	–	+	++

Signaling pathways

TCR signaling	+	++	+/−

IL-2 signaling	+	++	+/−

Pi3K–AKT–mTOR signaling	+	++	+/−

p38MAPK activation	–	–	+

	Early differentiation	Intermediate differentiation	Terminal differentiation

Cytotoxicity	–	+	++

Cytokine secretion (TNF-α, IFN-γ)	–	+	++

Signaling pathways

TCR signaling	+	++	+/−

IL-2 signaling	+	++	+/−

Pi3K–AKT–mTOR signaling	+	++	+/−

p38MAPK activation	–	–	+


Amendment	Concentration	mNa	Effectiveness

Aldrich Humic Acid	1 mg C L-1	0.7(0)	LS

5 mg C L-1	0.3(6)	LS

10 mg C L-1	0.3(7)	LS

IHSS Humic Acid	1 mg C L-1	0.8(4)	LS

5 mg C L-1	0.1(7)	LS

10 mg C L-1	0.1(9)	LS

IHSS Fulvic Acid	1 mg C L-1	0.7(7)	LS

5 mg C L-1	0.1(9)	LS

10 mg C L-1	0.1(7)	LS

MCC water	∼ 5 mg C L-1*	<0.1	NR

SR lake water	∼ 10 mg C L-1*	0.8(6)	LS

Amendment	Concentration	mNa

Aldrich Humic Acid	1 mg C L-1	0.7(0)

5 mg C L-1	0.3(6)

10 mg C L-1	0.3(7)

IHSS Humic Acid	1 mg C L-1	0.8(4)

5 mg C L-1	0.1(7)

10 mg C L-1	0.1(9)

IHSS Fulvic Acid	1 mg C L-1	0.7(7)

5 mg C L-1	0.1(9)

10 mg C L-1	0.1(7)

MCC water	∼ 5 mg C L-1*	<0.1

SR lake water	∼ 10 mg C L-1*	0.8(6)

Effectiveness

LS

LS

LS

LS

LS

LS

LS

LS

LS

NR

LS


Chromosome	AntiSMASH	SMURF	Unique NP

I	1	1	1

II	3	1	4

III	4	4	5

IV	3	1	4

V	6	6	7

VI	8	6	8

VII	7	6	7

Total	32	25	36


	n (%)

Primary clinical composite diagnoses

 Anterior cruciate ligament injury	8 (5)

 Meniscal injury	36 (20)

 Patellofemoral Pain Syndrome	45 (25)

 Osteoarthritis	79 (44)

 Other knee diagnoses	11 (6)

Imaging findings and diagnoses

 Osteoarthritis	96 (56)

K-L Grade 1	14 (15)

K-L Grade 2	36 (38)

K-L Grade 3	19 (20)

K-L Grade 4	13 (14)

 Meniscal tears (n)	54 (32)

Medial meniscus	49 (91)

Lateral meniscus	8 (15)

 Anterior cruciate ligament tears	16 (9)

Complete	6 (37)

Partial	8 (50)

Unclear	2 (13)

 Posterior cruciate ligament tear	1 (1)

 Soleus tear	1 (1)

 Hamstring tendinopathy	2 (1)

 Medial collateral ligament tear	1 (1)

Primary clinical composite diagnoses

Anterior cruciate ligament injury

Meniscal injury

Patellofemoral Pain Syndrome

Osteoarthritis

Other knee diagnoses

Imaging findings and diagnoses

Osteoarthritis

K-L Grade 1

K-L Grade 2

K-L Grade 3

K-L Grade 4

Meniscal tears (n)

Medial meniscus

Lateral meniscus

Anterior cruciate ligament tears

Complete

Partial

Unclear

Posterior cruciate ligament tear

Soleus tear

Hamstring tendinopathy

Medial collateral ligament tear


Part of Intestine	Control group	Pomegranate treated group	Sodium.butyrate treated group

Non-everted (μg)	Everted (μg)	Non-everted (μg)	Everted (μg)	Non-everted (μg)	Everted (μg)

Duodenum	12.4±0.14	13.1±0.2	7.07± 1.0	12.29±0 .7	11.9±1.0 †	15.5±0.3

Jejunum	13.3±0.66	15.2±0.2	8.96±0 .32	11.87±0.3	13.4±0 .4†	14.3±0.3

Ileum	9.97±0.77	17.1±0.3	7.97±0.05	14.82 ±0.4	10.3±0.8	16.8±0.8†

Colon	9.57±0.48	14.0±0.2	6.85±0.7	9.89±0.1	9.7±1.2†	14.5±0.3†

Part of Intestine	Control group	Pomegranate treated group	Sodium.butyrate treated group

Non-everted (μg)	Everted (μg)	Non-everted (μg)	Everted (μg)	Non-everted (μg)

Duodenum	12.4±0.14	13.1±0.2	7.07± 1.0	12.29±0 .7	11.9±1.0 †

Jejunum	13.3±0.66	15.2±0.2	8.96±0 .32	11.87±0.3	13.4±0 .4†

Ileum	9.97±0.77	17.1±0.3	7.97±0.05	14.82 ±0.4	10.3±0.8

Colon	9.57±0.48	14.0±0.2	6.85±0.7	9.89±0.1	9.7±1.2†

Sodium.butyrate treated group

Everted (μg)

15.5±0.3

14.3±0.3

16.8±0.8†

14.5±0.3†


	Discharged	Expired

	32	18

Tracheostomy	26.5	23.5

	1.141	1.30

	21	29

Non Tracheostomy	26.5	23.5

	1.141	1.30


 	BRCA1	BRCA2	Non-BRCA1/2

All males in kConFab registry	429	339	19137

Breast Cancers	5 (1.2%)	35 (10.3%)	78 (0.4%)

Pathology Available	3	25	32


Patients with HPA	Gender	Age	Mechanism of trauma	Liver injury grade*	Symptoms of HPA	Blood transfusion

1	Female	25	Blunt	2	No	No

2	Male	20	Blunt	2	Yes	Yes

3	Male	45	Blunt	2	No	No

4	Male	9	Blunt	3	No	No

5	Male	30	Blunt	3	Yes	Yes

6	Female	42	Blunt	4	No	No

7	Male	42	Blunt	4	No	No

Patients with HPA	Gender	Age	Mechanism of trauma	Liver injury grade*	Symptoms of HPA

1	Female	25	Blunt	2	No

2	Male	20	Blunt	2	Yes

3	Male	45	Blunt	2	No

4	Male	9	Blunt	3	No

5	Male	30	Blunt	3	Yes

6	Female	42	Blunt	4	No

7	Male	42	Blunt	4	No

Blood transfusion

No

Yes

No

No

Yes

No

No


Age groups of Males/females 	Quantity of interviewees

50-60 (10 males)	10

63-69 (20 males/5 females)	25

70-75 (10 male hakims/7 females)	17

75-80 (8 female)	8

Age groups of Males/females

50-60 (10 males)

63-69 (20 males/5 females)

70-75 (10 male hakims/7 females)

75-80 (8 female)


Branch and Terminal Node Number and Description	N	AT%	Mean Distance

Node	Suburban branch

1.	Front porch > 0.83, driveways < 0.83, sidewalks > 0.67	136	7 4,8,9,11,12	1366.45 2,4–12

2.	Blank walls > 0.26, front porch < 0.83, driveways < 0.83, sidewalks > 0.67	39	23 8,9,11,12	688.55 1,4,5,11,12

3.	Blank walls < 0.26, front porch < 0.83, driveways < 0.83, sidewalks > 0.67	8	75	1245.7412

	Urban branch

4.	Zebra crosswalks < 0.03, driveways > 0.83, sidewalks > 0.67	137	23 1,8,9,11,12	1123.83 1,2,6–12

5.	Traffic/pedestrian signals > 0.44, zebra crosswalks > 0.03, driveways > 0.83, sidewalks > 0.67	60	25 8,9,11,12	1105.56 1,2,6–12

6.	Curb cut < 0.91, decorative sidewalks > 0.21, zebra crosswalks > 0.03, driveways > 0.83, sidewalks > 0.67	31	29 9,11,12	464.75 1,4,5,7,8,10,12

7.	Sidewalk buffer > 0.93, curb cut > 0.91, decorative sidewalks > 0.21, traffic/pedestrian signals < 0.44, zebra crosswalks > 0.03, driveways > 0.83, sidewalks > 0.67	24	42 1,2	739.21 1,4–6,9,11,12

8.	Sidewalk buffer < 0.93, curb cut > 0.91, decorative sidewalks > 0.21, traffic/pedestrian signals < 0.44, zebra crosswalks > 0.03, driveways > 0.83, sidewalks > 0.67	14	79 1,2,4,5	739.6 1,4–6,9,11,12

9.	Decorative sidewalks < 0.21, traffic/pedestrian signals < 0.44, zebra crosswalks > 0.03, driveways > 0.83, sidewalks > 0.67	26	77 1,2,4–6	401.25 1,4,5,7,8,10,12

	Alley branch

10.	Crosswalks < 0.14, convenient to cross segment < 0.15, sidewalks > 0.67	18	39 1,2	774.1 1,4–6,9,11,12

11.	Crosswalks > 0.14, convenient to cross segment < 0.15, sidewalks > 0.67	18	78 1,2,4–6	297.85 1,2,4,5,7,8,10

12.	Convenient to cross segment > 0.15, sidewalks < 0.67	25	100 4,8,9,11,12	137.18 1–10


# Gene ID Gene Description

AKAP11 A-kinase anchor protein 11 2

AKR1A1 alcohol dehydrogenase 3

ATP5O ATP synthase subunit O, mitochondrial precursor 4

C1orf109 hypothetical protein LOC54955 5

C2orf29 hypothetical protein LOC55571 6

C9orf123 transmembrane protein C9orf123 7

CDK9 cell division protein kinase 9 8

CHSY1 chondroitin sulfate synthase 1 9

CKAP2L cytoskeleton-associated protein 2-like 10

CLINT1 clathrin interactor 1 11

DUSP2 dual specificity protein phosphatase 2 12

DUSP6 dual specificity protein phosphatase 6 isoform 13

HSPC157 hypothetical LOC29092 14

KIAA0427 CBP80/20-dependent translation initiation factor 15

LDHA L-lactate dehydrogenase A chain isoform 5 16

LOC100188949 hypothetical LOC100188949 17

LOC285456 hypothetical LOC285456 18

LSM14B protein LSM14 homolog B 19

MAX protein max isoform a 20

MRPS18A 28S ribosomal protein S18a, mitochondrial 21

MTF2 metal-response element-binding transcription 22

NAIF1 nuclear apoptosis-inducing factor 1 23

NDUFA10 NADH dehydrogenase [ubiquinone] 1 alpha 24

POMP proteasome maturation protein 25

PSMA6 proteasome subunit alpha type-6 26

RBM16 putative RNA-binding protein 16 27

RBM38 RNA-binding protein 38 isoform a 28

RPN1 dolichyl-diphosphooligosaccharide--protein 29

SEPHS2 selenide, water dikinase 2 30

SIRPG signal-regulatory protein gamma isoform 1 31

SPRED2 sprouty-related, EVH1 domain-containing protein 32

TFRC transferrin receptor protein 1 33

TMEM18 transmembrane protein 18 34

TRIP13 thyroid receptor-interacting protein 13 isoform 35

TXN2 thioredoxin, mitochondrial precursor 36

UBE2D2 ubiquitin-conjugating enzyme E2 D2 isoform 1 37

ZFAT zinc finger protein ZFAT isoform 1 38

ZNF212 zinc finger protein 212 39

ZNF683 zinc finger protein 683

# Gene ID Gene Description

ZNF212 zinc finger protein 212 39

ZNF683 zinc finger protein 683


Part	Number of sub-parts	Number of guidance points

Leadership	8	93

Policy and strategy	5	43

People management	6	60

Resources	7	54

Processes	4	29

Customer and society results	2	43

People results	2	36

Contractor results	2	33

Key performance results	2	19

Total	38	410

Part	Number of sub-parts	Number of guidance points

People results	2	36

Contractor results	2	33

Key performance results	2	19

Total	38	410


Variable		N (92,082)	% (100.0)

gnosed hypertension	s	40	0.7

No	72,985	79.3

Physician-diagnosed diabetes	Yes	7991	8.7

No	84,050	91.3


	Nutridrink	Impact	Return to Nutridrink	p

Body weight (kg)	57 ± 5.8	57 ± 5.9	58 ± 5.8	NS

Systolic BP (mmHg)	115 ± 11	110 ± 7	117 ± 11	0.012

Diastolic BP (mmHg)	69 ± 9	64 ± 8	69 ± 9	0.03

Heart rate (pulse/min)	88 ± 15	77 ± 17	80 ± 14	0.002

BMI (kg/m2)	18.8 ± 1.7	18.9 ± 1.6	19 ± 1.6	NS

	Nutridrink	Impact

Body weight (kg)	57 ± 5.8	57 ± 5.9

Systolic BP (mmHg)	115 ± 11	110 ± 7

Diastolic BP (mmHg)	69 ± 9	64 ± 8

Heart rate (pulse/min)	88 ± 15	77 ± 17

BMI (kg/m2)	18.8 ± 1.7	18.9 ± 1.6


Independent variables 	Model 1	Model 2	Model 3

Health-related risk factors

 Medical conditions (index)	−0.134***	−0.052***	−0.036*

 Mobility difficulties (index)	−0.273***	−0.115***	−0.079***

 Activity limitations (index)	−0.504***	−0.196***	−0.168***

Sociodemographic variables

 Age (cont.)	 	 	−0.104***

 Language: Swedish (ref. Finnish and others)	 	 	0.068***

 Gender: female (ref. male)	 	 	0.056***

 Civil status: partnership (ref. single)	 	 	0.052***

 Income: high (ref. low)	 	 	0.062***

 Education: high (ref. low education)	 	 	0.083***

 Country: Sweden (ref. Finland)	 	 	−0.015

n	 	5435	5435

Adjusted R square	 	0.071	0.101


Test Type	5-Option Version (n = 25)	2-Option Version (n = 37)

	Without OPC	With OPC*	Without OPC	With OPC**

FOBT	21%	17%	32%	54%

Sigmoidoscopy	4%	8%	-	-

FOBT & Sigmoidoscopy	21%	21%	-	-

Colonoscopy	46%	42%	68%	41%

Barium Enema	4%	8%	-	-

No Screening	4%	4%	-	5%

Test Type	5-Option Version (n = 25)	2-Option Version (n = 37)

	Without OPC	With OPC*	Without OPC

FOBT	21%	17%	32%

Sigmoidoscopy	4%	8%	-

FOBT & Sigmoidoscopy	21%	21%	-

Colonoscopy	46%	42%	68%

Barium Enema	4%	8%	-

No Screening	4%	4%	-

2-Option Version (n = 37)

With OPC**

54%

-

-

41%

-

5%


	Overall	Chronic kidney disease at baseline	p values

(n = 162)	Present (n = 25)	Absent (n = 137)

, %)	3	48	30	08


Time from onset of illness 	Signs/symptoms	Drug exposure 	Laboratory values

ALT	ALP	Total bilirubin	Direct bilirubin	Misc.

−5	Sore throat	Amoxicillin started

0	Fever, anorexia, dysphagia, neck swelling, and cervical lymphadenopathy	Ceftriaxone and vancomycin started

3–5	Worsening of neck swelling	Ceftriaxone and vancomycin discontinued, and ampicillin/sulbactam and steroid started

5–10	Diarrhea	Ampicillin/sulbactam and steroid discontinued, and clindamycin and probiotics started

10	Fever, headache, dizziness, chest pain on coughing, and dark urine. Hepatosplenomegaly, RUQ tenderness	Clindamycin switched to ampicillin/sulbactam	406	404	3.0	2.7

16–23	Generalized maculopapular rash and pruritus 	Ampicillin/sulbactam	152	737	8.8

25–30	Abdominal pain, vomiting. Hepatomegaly	Ampicillin/sulbactam	124	780	9.9	 	AST 130

48	Chest pain, fatigue, pruritus, acholic stools, and jaundice	 	138	713	13.4	8.8	Cholesterol 1044, GGT 347,

53	Increasing pruritus, anorexia	 	117	651	12.7	8.5	GGT 294

67	Anorexia, pruritus	 	48	493	12.6	8.7	GGT 77

83	Anorexia	 	83	497	8.3	5.5	GGT 273

111	No anorexia	 	51	670	2.3	1.2	GGT 507

Time from onset of illness	Signs/symptoms	Drug exposure	Laboratory values

ALT	ALP

−5	Sore throat	Amoxicillin started

0	Fever, anorexia, dysphagia, neck swelling, and cervical lymphadenopathy	Ceftriaxone and vancomycin started

3–5	Worsening of neck swelling	Ceftriaxone and vancomycin discontinued, and ampicillin/sulbactam and steroid started

5–10	Diarrhea	Ampicillin/sulbactam and steroid discontinued, and clindamycin and probiotics started

10	Fever, headache, dizziness, chest pain on coughing, and dark urine. Hepatosplenomegaly, RUQ tenderness	Clindamycin switched to ampicillin/sulbactam	406	404

16–23	Generalized maculopapular rash and pruritus	Ampicillin/sulbactam	152	737

25–30	Abdominal pain, vomiting. Hepatomegaly	Ampicillin/sulbactam	124	780

48	Chest pain, fatigue, pruritus, acholic stools, and jaundice		138	713

53	Increasing pruritus, anorexia		117	651

67	Anorexia, pruritus		48	493

83	Anorexia		83	497

111	No anorexia		51	670

Laboratory values

Total bilirubin	Direct bilirubin	Misc.

3.0	2.7

8.8

9.9		AST 130

13.4	8.8	Cholesterol 1044, GGT 347,

12.7	8.5	GGT 294

12.6	8.7	GGT 77

8.3	5.5	GGT 273

2.3	1.2	GGT 507


Inclusion criteria	Exclusion criteria

Original research articles referring to noninvasive modalities or minimally invasive techniques to accelerate orthodontic tooth movementAnimal studies	Randomized clinical trialsArticles dealing with highly invasive proceduresArticles referring to use of biochemical or drugs to accelerate tooth movementMicroimplants or frictionless brackets as a modality to reduce treatment duration Reviews, interviews, and discussions

Inclusion criteria

Original research articles referring to noninvasive modalities or minimally invasive techniques to accelerate orthodontic tooth movementAnimal studies

Exclusion criteria

Randomized clinical trialsArticles dealing with highly invasive proceduresArticles referring to use of biochemical or drugs to accelerate tooth movementMicroimplants or frictionless brackets as a modality to reduce treatment duration Reviews, interviews, and discussions


Area	Parameter estimate (SE)	t‐Value (P‐value) for parameter difference from zero	t‐Values (P‐values) for differences of least squares means

Garbage	Light	Lawn	Other modified	Natural

Garbage	2.92 (0.52)	5.61 (<0.0001)		2.66 (0.08)	4.34 (<0.01)b	4.11 (<0.01)b	5.61 (<0.0001)b

Under lights	1.47 (0.60)	2.46 (0.01)			0.96 (0.87)	1.37 (0.65)	2.46 (0.12)

Lawn	0.89 (0.58)	1.54 (0.13)				0.48 (0.99)	1.54 (0.54)

Other modified	0.60 (0.63)	0.94 (0.35)					0.94 (0.88)

Natural	0a

Area	Parameter estimate (SE)	t‐Value (P‐value) for parameter difference from zero	t‐Values (P‐values) for differences of least squares means

Garbage	Light	Lawn	Other modified	Natural

her modified	.63)	.94 (0.35)					)

Natural	0a


Locus	Primer sequences (5′–3′)	Primer sequences (5′–3′)

b50	F: AACAATCCAGGAGTGGCAATC	R: ACAAGCGAAGATCGTCTCATC

b35	F: CGTTCAGTCACCAGCAAGG	R: GAGGGAAGCAGGGAGAGC

b38	F: TAATCCCTCAATGGCTCTTTTC	R: GAGAAGGATACGAATTGACAGG

b40	F:TGTATAGAACTGAGTAAATGATTG	R: CAACTTTCTTAAACCACTTTCG

b43	F: CGAGCCTTCTTCTTCTTCTGG	R: GCAAGCAATACGGACAGTAGG

c03	F:CGTGAAAATAGTGATATGTGTG	R: ACTGTAACAATCAAGAAGAAACC

c07	F:GCCACAGCCGAGGAAGAG	R: TCTCATCACCACCACCTTAGG

b27	F: AGCCAGGTTCCAGAAGTCC	R: CATAATCACAAAGTCTCGGTTCC

b28	F: TCCCACCACGGACTACTG	R: AACCACCATCATCATCATCATC

b11	F: GCGGAGGCTTAATTTGCTTTG	R: ACTCAATACATACACGGCACTAG

b16	F: ACCTCTACGGACCTCTTCTTC	R: CATAACATAACATGACACACAAGC

b24	F: GAGCCAGAGCCAGGTTCC	R: ACAAAGTCTCGGTTCCTTACAC

b34	AATAGAATGTGGAGGCGATAGAG	R: AAACCATAAATCAACTACCGAACC

b64	F: CTTGAGATACAGCCTTCCATTAG	R: CACACCTCGCTTCCCTTG

c17	F:GAAACTATTTCCACCAACAAAG	R: ACACACATTCCTACACACC

b57	F: CGGATATGGTGGAGGTTATGC	R: CAGAACGACGACGACGAC

b65	F: ACGAACCACAACACAGAGAG	R: ACGAGGGAACACCAGAGAG

c18	F:AAGCCGAGCGTGAAGAAG	R: ACACACAGAAAGAACACAAGAC

b53	F: GGCTCAAGTTTGCTCATAGATTC	R: CGGCTTCGCTTTAGGATTTG

b56	F: CGGTCTGTGGATACGAATGG	R: GACGACGACGACGATGATG

c10	F:AGTGCGGAGATAACTGTTC	R: GGCTACTTTATTCTAAACCAAAC

Locus	Primer sequences (5′–3′)

b50	F: AACAATCCAGGAGTGGCAATC

b35	F: CGTTCAGTCACCAGCAAGG

b38	F: TAATCCCTCAATGGCTCTTTTC

b40	F:TGTATAGAACTGAGTAAATGATTG

b43	F: CGAGCCTTCTTCTTCTTCTGG

c03	F:CGTGAAAATAGTGATATGTGTG

c07	F:GCCACAGCCGAGGAAGAG

b27	F: AGCCAGGTTCCAGAAGTCC

b28	F: TCCCACCACGGACTACTG

b11	F: GCGGAGGCTTAATTTGCTTTG

b16	F: ACCTCTACGGACCTCTTCTTC

b24	F: GAGCCAGAGCCAGGTTCC

b34	AATAGAATGTGGAGGCGATAGAG

b64	F: CTTGAGATACAGCCTTCCATTAG

c17	F:GAAACTATTTCCACCAACAAAG

b57	F: CGGATATGGTGGAGGTTATGC

b65	F: ACGAACCACAACACAGAGAG

c18	F:AAGCCGAGCGTGAAGAAG

b53	F: GGCTCAAGTTTGCTCATAGATTC

b56	F: CGGTCTGTGGATACGAATGG

c10	F:AGTGCGGAGATAACTGTTC

Primer sequences (5′–3′)

R: ACAAGCGAAGATCGTCTCATC

R: GAGGGAAGCAGGGAGAGC

R: GAGAAGGATACGAATTGACAGG

R: CAACTTTCTTAAACCACTTTCG

R: GCAAGCAATACGGACAGTAGG

R: ACTGTAACAATCAAGAAGAAACC

R: TCTCATCACCACCACCTTAGG

R: CATAATCACAAAGTCTCGGTTCC

R: AACCACCATCATCATCATCATC

R: ACTCAATACATACACGGCACTAG

R: CATAACATAACATGACACACAAGC

R: ACAAAGTCTCGGTTCCTTACAC

R: AAACCATAAATCAACTACCGAACC

R: CACACCTCGCTTCCCTTG

R: ACACACATTCCTACACACC

R: CAGAACGACGACGACGAC

R: ACGAGGGAACACCAGAGAG

R: ACACACAGAAAGAACACAAGAC

R: CGGCTTCGCTTTAGGATTTG

R: GACGACGACGACGATGATG

R: GGCTACTTTATTCTAAACCAAAC


Phases	Contacted	Screening1a	Screening2b	Screening3c	Successfully recruited

IG	CG

Run-in	214	184 (86)	106 (50)	109 (51)	50 (23)	50 (23)

Main	488	378 (78)	306 (63)	300 (62)	140 (29)	140 (29)


Second-level category	n (%)

b140 attention functions	149 (85)

b130 energy and drive functions	127 (73)

b147 psychomotor functions	124 (71)

b760 control of voluntary movement functions	114 (65)

b164 higher-level cognitive functions	106 (61)

b152 emotional functions	90 (51)

b126 temperament and personality functions	64 (37)

b125 dispositions and intra-personal functions	58 (33)

b144 memory functions	55 (31)

b117 intellectual functions	31 (18)

b156 perceptual functions	31 (18)

b134 sleep functions	30 (17)

b180 experience of self and time functions	26 (15)

b235 vestibular functions	19 (11)

b735 muscle tone functions	15 (9)

b260 proprioceptive functions	14 (8)

b160 thought functions	12 (7)

b210 seeing functions	12 (7)

b230 hearing functions	11 (6)

b110 consciousness functions	10 (6)

b122 global psychosocial functions	10 (6)

b163 basic cognitive functions	10 (6)

b114 orientation functions	9 (5)

b167 mental functions of language	9 (5)

b280 sensation of pain	9 (5)

b330 fluency and rhythm of speech functions	9 (5)

b765 involuntary movement functions	9 (5)

b176 mental function of sequencing complex movements	8 (5)

b265 touch function	8 (5)

b270 sensory functions related to temperature and other stimuli	8 (5)


	Total number	Gleason grade group 1	Gleason grade group 2	Gleason grade group 3	Gleason grade group 4	Gleason grade group 5

N° of primary tumors	60	12	12	12	12	12

N° of CD44v8-10	24	3	3	5	6	5

% positive tumors	40%	25%	25%	42%	50%	42%


 	Boys	Girls

 	Verbal abuse	Threat of violence	Physical assault	Verbal abuse	Threat of violence	Physical assault

Verbal abuse	1.00	 	 	1.00

Threat of violence	0.35*	1.00	 	0.34*	1.00

Physical assault	0.27*	0.52*	1.00	0.23*	0.36*	1.00


 	Clinical setting

Barrier	HTN & eGFR ≥ 60 (%)	HTN & eGFR < 60 (%)

No impact on management	37	24

Limited time/more urgent patient issues	25	20

Not recommended by guidelines	25	11

Cost	13	9

Poor patient adherence	5	5

	Clinical setting

Barrier	HTN & eGFR ≥ 60 (%)

No impact on management	37

Limited time/more urgent patient issues	25

Not recommended by guidelines	25

Cost	13

Poor patient adherence	5

Clinical setting

HTN & eGFR < 60 (%)

24

20

11

9

5


Progression to PID	Fraction progressing, % (95% CI)*	Cumulative incidence of PID after one year, % (95% CI)†	Akaike’s Information Criterion‡

Control group	Intervention group

Data

Results from RCT	 	1.9 (1.2 to 2.9)	1.3 (0.7 to 2.1)

Model

Immediate progression	8.3 (5.7 to 11.0)	1.6 (1.1 to 2.1)	1.6 (1.1 to 2.1)	13.3

Constant progression	9.9 (6.8 to 13.0)	1.7 (1.2 to 2.3)	1.5 (1.0 to 1.9)	12.1

Progression at the end	10.0 (6.8 to 13.1)	1.7 (1.2 to 2.3)	1.5 (1.0 to 1.9)	12.1

Progression to PID	Fraction progressing, % (95% CI)*	Cumulative incidence of PID after one year, % (95% CI)†	Akaike’s Information Criterion‡

Control group	Intervention group

Data

Results from RCT		1.	1.3


Fc γ IIA genotype	Mild (<8)	Moderate (8–18)	Severe (>18)


 	Pharmacologic intervention title: ‘Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomized placebo-controlled trial’ [28]	Non-pharmacologic intervention title: ‘Treatment of childhood obesity by retraining eating behaviour: randomized controlled trial’ [29]

Active ingredients	Vitamins C and E	Not reported

Comparator	Placebo	Not reported

Health condition	Pre-eclampsia	Obesity

Eligibility criteria	Women with type 1 diabetes	Children

Objective	Prevention of pre-eclampsia	Retraining eating behaviour

Trial design	Randomized controlled trial	Randomized controlled trial


Item	N-free	Soybean meal	Rapeseed meal	Canola meal

Ingredients (%)


Matrix Mechanical Characteristics that Impact Cell or Tissue Function

• Pore size and morphology (Chan et al., 2008); [142]

• Elasticity (Janson et al., 2015); [131]

• Stiffness (Xia et al., 2017); [143]

• Hydration degree (Wu et al., 2006); [140]

Matrix Mechanical Characteristics that Impact Cell or Tissue Function

• Stiffness (Xia et al., 2017); [143]

• Hydration degree (Wu et al., 2006); [140]


Name	SNP	Primer	Product length (bp)	Primer sequence (5’→3’)

rs17576	A/G	Forward		CAATTCACCCTCCCGCACTC

		Reverse	222	GGAAGATGAATGGAAACTGG

rs2250889	C/G	Forward		GTATTTGTTCAAGGATGGGTG

		Reverse	367	AGACGTTTCGTGGGTTAT


Material	Tested	Ref.

Boron nitride, BN	Tested, in use, high efficiency, low erosion (0.02 mm3/C at 300 V)	131, 139, 140

Borosil, BN + SiO2	Tested, in use, high efficiency, low wear	131, 141

Alumina, Al2O3	Tested, medium efficiency, low erosion (0.01 mm3/C at 300 V)	139, 141

Silicon carbide, SiC	Tested, medium efficiency, medium erosion	131

Graphite	Tested, low efficiency, high erosion	65

Nanocrystalline diamond	Tested, high efficiency, low erosion	131, 142

CVD diamond	Tested for wear, lower erosion	63

Ultra-BN, uBN	Tested, high efficiency, very low wear	New result


 	HAZ	WAZ

 	Coefficient	Percent of ∆	Coefficient	Percent of ∆

Raw gap, ∆	.379	100.00	.248	100.00

Of which:

 Explained	.234	61.7	.164	66.3

 Unexplained	.145	38.3	.083	33.7

	HAZ

	Coefficient

Raw gap, ∆	.379

Of which:

Explained	.234

Unexplained	.145


Sub-scale	Attitudinal items	Surgeon (n=41)	Anaesthetist (n= 33)	Nurse (n=33)

 	 	Mode	IQR	Mode	IQR	Mode	IQR

 	There is little difference between the surgical checklist at GUH and the WHO surgical checklist.	3	2	1	3.25	2	2.75

Norms	The complete checklist is used for every procedure in every theatre at UHG.	2	3	1	3	5	1

 	The complete checklist is used for every procedure in which I am involved in theatre.	5	1.5	1	3	5	1

 	When the checklist is being carried out, everyone in theatre stops what they are doing and listens until it is completed.	1	3	1	1	1	1.5

 	Sometimes sections of the checklist are not completed.*	4	2	4	2	4	1

 	The individual who signs the checklist personally ensures that the relevant steps have been completed.	5	1.5	4	2	4	1

Impact on teamwork & safety	I believe that failing to use the checklist is poor professional practice.	5	1	5	1	5	0

 	I believe using the checklist reduces the likelihood of human error.	5	0.75	5	1	5	0

 	I believe using the checklist improves patient safety.	5	0.5	5	1	5	0

 	I believe using the checklist improves teamwork in theatre.	5	1	5	1	5	1

 	The use of the checklist should be mandatory for every case.	5	1	5	1	5	0

Support	Surgical personnel support the use of the checklist.	5	1	4	1	5	5

 	Anaesthetic personnel support the use of the checklist.	4	2	4	1	5	4

 	Nursing staff support the use of the checklist.	5	0	4	1	5	5

 	Senior theatre personnel support the use of the checklist.	5	2	4	1	5	5

 	Junior theatre personnel support the use of the checklist.	5	1	4	1	5	5

 	Management support the use of the checklist.	5	2	5	1	5	5

Initiate	I have initiated the use of the checklist in the past.	5	2	1	3	5	0

 	I intend to initiate the use of the checklist in the future.	5	1	3	1.75	5	0

Barriers	The requirement for signatures.	4	2.5	5	3	5	1

 	Lack of assertiveness of staff.	4	2	4	2.5	4	1

 	Lack of time.	4	2	4	2.75	4	1

 	Lack of training.	4	2	4	2	4	1.5

 	The lack of an electronic version of the checklist.	3	2	5	3	3	2


Research problem	Tool/Instrument	Authors

Nausea and vomiting	Nausea Vomiting Pregnancy QOL (NVP QOL)	[8] Canada

Pregnancy Unique Questionnaire Emesis (PUQE)	[9] Canada, [10] Canada

McGill nausea questionnaire	[11] Canada

Rhodes’ scores (RI)	[12] Canada

Short form – 36 (SF-36)	[13] China

SF-12, NVP specific QOL	[14] Canada

NVPQOL, SF-36, SCL90	[15] USA

Irritable bladder	Incontinence Impact Questionnaire (IIQ), Urogenital Distress Inventory (UDI)	[6] Netherlands

Incontinence Questionnaire Short Form (ICIQ-SF)	[16] Turkey

Back pains	Nottingham Health Profile (NHP) Disability Rating Index (DRI)	[17] Sweden

Pregnancy Mobility Index (PMI)	[18] Netherlands

WHOQOL-BREF	[19] Turkey

Anxiety and depression	Finnish modification of SF of the beck depression inventory and anxiety	[20] Finland

Hospital Anxiety and Depression Scale (HADS)	[21] Sweden

EPDS, SF-36v2	[22] China

WHOQOL-BREF, EPDS	[23] Austria

Research problem	Tool/Instrument	Authors

Nau	Nausea Vomiting Pregnancy QOL (NVP QOL)	[8] Canada

Pregnancy Unique Questionnaire Emesis (PUQE)	[9] Canada, [10] Canada

McGill nausea question

Research problem	Tool/Instrument	Authors

sea and vomiting	naire	[11] Canada

Rhodes’ scores (RI)	[12] Canada

Short form – 36 (SF-36)	[13] China

SF-12, NVP specific QOL	[14] Canada

NVPQOL, SF-36, SCL90	[15] USA

Irritable bladder	Incontinence Impact Questionnaire (IIQ), Urogenital Distress Inventory (UDI)	[6] Netherlands

Incontinence Questionnaire Short Form (ICIQ-SF)	[16] Turkey

Back pains	Nottingham Health Profile (NHP) Disability Rating Index (DRI)	[17] Sweden

Pregnancy Mobility Index (PMI)	[18] Netherlands

WHOQOL-BREF	[19] Turkey

Anxiety and depression	Finnish modification of SF of the beck depression inventory and anxiety	[20] Finland

Hospital Anxiety and Depression Scale (HADS)	[21] Sweden

EPDS, SF-36v2	[22] China

WHOQOL-BREF, EPDS	[23] Austria


Laboratory site	Samples (n)	Number of devices (n)	Runs per day (n)	Approximately overall time requirement

		Sprinter XL	EUROPattern	Screening	Titer

Houston, TX, USA	141	1	1	1	1	06:00 h

Tampa, FL, USA	134	1	1	1	1	06:10 h

Dallas, TX, USA	187	1	1	1	1	06:40 h

Phoenix, AZ, USA	231	1	1	1	1	07:10 h

Birmingham, AL, USA	236	2	2	2	1	06:30 h

Burlington, NC, USA	471	2	2	2	2	07:10 h

Dublin, OH, USA	330	2	2	2	2	07:10 h

Raritan, NJ, USA	568	3	3	3	3	07:05 h

Laboratory site	Samples (n)	Number of devices (n)	Runs per day (n)	Approximately overall time requirement

		Sprinter XL	EUROPattern	Screening	Titer

Tampa, FL, USA	134	1	1	1	1	06:10 h

Dallas, TX, USA	187	1	1	1	1	06:40 h

Phoenix, AZ, USA	231	1	1	1	1	07:10 h

Birmingham, AL, USA	236	2	2	2	1	06:30 h

Burlington, NC, USA	471	2	2	2	2	07:10 h

Dublin, OH, USA	330	2	2	2	2	07:10 h

Raritan, NJ, USA	568	3	3	3	3	07:05 h


School	Arm allocationa	Number of girls in school	Provided consent (n, %)	Enrolled in intervention (n, %)	Provided baseline data (n, %)	Mean weekly attendance during intervention (n, %)

					Questionnaire	Accelerometerb

1	A	106	43 (40.6)	30 (28.3)	30 (100)	28 (93.3)	15.4 (51.3)

2		10	43 (43.	30 (3	30	29 (9	2


Characteristic	β	Standard error	P

Baseline	-5.169	1.388	0.000

Proband breast cancer diagnosis ≤35 years	2.791	1.379	0.043

Proband breast cancer diagnosis 36-39 years	2.248	1.365	0.100

Proband breast cancer diagnosis 40-49 years	1.763	1.355	0.193

Proband breast cancer diagnosis 50-59 years	1.065	1.354	0.431

Proband bilateral breast cancer at any age	1.036	0.462	0.025

Proband ovarian cancer at any age	0.238	1.469	0.871

Proband triple-negative breast cancer at any age	1.323	0.331	0.000

For each relative with cancer:

 First degree, breast cancer diagnosis ≤39 years	0.950	0.369	0.010

 First degree, breast cancer diagnosis 40-49 years	1.450	0.386	0.000

 First degree, breast cancer diagnosis 50-59 years	1.445	0.450	0.001

 First degree, breast cancer diagnosis 60+ years	0.207	0.646	0.749

 First degree, ovarian cancer at any age	2.556	0.769	0.001

 Second degree, breast cancer diagnosis at any age	0.359	0.272	0.187

 Second degree, ovarian cancer diagnosis at any age	1.861	0.832	0.025

Characteristic	β	Standard error	P

Baseline	-5.169	1.388	0.000

Proband breast cancer diagnosis ≤35 years	2.791	1.379	0.043

Proband breast cancer diagnosis 36-39 years	2.248	1.365	0.100

Proband breast cancer diagnosis 40-49 years	1.763	1.355	0.193

Proband breast cancer diagnosis 50-59 years	1.065	1.354	0.431

Proband bilateral breast cancer at any age	1.036	0.462	0.025

Proband ovarian cancer at any age	0.238	1.469	0.871

Proband triple-negative breast cancer at any age	1.323	0.331	0.000

For each relative with cancer:

First degree, breast cancer diagnosis ≤39 years	0.950	0.369	0.010

First degree, breast cancer diagnosis 40-49 years	1.450	0.386	0.000

First degr		0.45	0.00

Characteristic	β	Standard error	P

ee, breast cancer diagnosis 50-59 years	1.445	0	1

First degree, breast cancer diagnosis 60+ years	0.207	0.646	0.749

First degree, ovarian cancer at any age	2.556	0.769	0.001

Second degree, breast cancer diagnosis at any age	0.359	0.272	0.187

Second degree, ovarian cancer diagnosis at any age	1.861	0.832	0.025


 	Normal thyroid (n.4)	Hyperplasia/Benign nodules (n.5)	Thyroid carcinoma (n.7)

Video intensity UCAIGg

Video intensity difference	11.3 (9.4-14.7)	12.2 (8.5-19.6)	19.4 (11.4-22.6)

Video intensity UCAVEGFR2

Video intensity difference	10.9 (10.3-14.9)	13.3 (10.8-15.8)	30.1 (25.1-35.6)* §


	Mechanism of action	Drugs	Trial (reference)	Study population	Benefits	Common severetoxicities

Apoptosis	PARP inhibitors	Olaparib	Phase II (127)	Recurrent/metastatic adult ES (failure to prior CH), n = 12 patients	NO responses SD: 4 patients, TTP: 5.7 weeks	No significant toxicities

	Heat shock protein inhibitors	Retaspimycin (Hsp-90 INH)	Phase I (128)	Metastatic and/or unresectable STS, n = 54 patients	PR: 2 patients (proof of clinical activity)	Grade 3–4:Fatigue Nausea and vomiting Headache Artharalgia

	Proteaseome inhibitor	Bortezomib	Phase II (129)	Metastatic OS, ES, RMS, and STS with no prior treatment for advanced disease, n = 25 patients	Lack of benefit (trial prematurely closed)	Grade 3–4:Neuropathy Asthenia Myalgias

	MDM2 inhibitor	RG7112	Proof of mechanism study (130)	WDLS or DDLS with MDM2 amplification receive RG7112 prior to surgery, n = 20 patients	SD: 14 patients, IHQ: activation of p53 pathway	Grade 3–4Neutropenia Thrombocytopenia

			Phase I (131)	Phase I trial with extension cohort for sarcoma patients, n = 30 (sarcoma patients)	Metabolic responses (PET-CT) IHQ: activation of p53 (MDM2-independent)	Grade 3–4 Cytopenias

	PI3K-AKT-mTOR pathway inhibitors	Ridaforolimus (mTOR INH)	Phase II (132)	Pre-treated advanced bone and STS, n = 212 patients	RR: 1.9%, clinical benefit: 28.8%	Grade 3–4Fatigue Stomatitis Hypertriglyceridemia Anemia Thrombocytopenia

			Phase III (133)	Advanced bone and STS with clinical benefit to previous CH were randomized to maintenance Ridaforolimus or Placebo, n = 711 patients	Improvement in PFS (17.7 weeks with Ridaforolimus vs. 14.6 weeks with Placebo, HR: 0.72, p: 0.001)	Similar to previous study

		Everolimus (mTOR INH)	Phase II (134)	Pre-treated advanced bone and STS, n = 41 patients	Poor clinical activity	Grade 3–4Hyperglicemia Stomatitis Pain Asthenia

	Anti-angiogenic therapy	Sorafenib (VEGFR2, VEGFR3, PDGFR, and c-Kit INH)	Phase II (135)	Pre-treated advanced STS, n = 101 patients	RR: 14.5%, SD: 32.9% (leiomyosarcoma better PFS)	Grade 3–4Fatigue Diarrhea Hand–foot Syndrome Nausea and vomiting

		Pazopanib (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR, and c-Kit INH)	Phase III (136)	Pre-treated non-adipocytic STS randomized to PAZOPANIB vs. PLACEBO, n = 369 patients	Improvement in PFS (4.6 months with PAZOPANIB vs. 1.6 months with Placebo, HR: 0.31, p < 0.0001)	Grade 3–4Asthenia Hypertension Anorexia Alteration of transaminases

Mitotic catastrophe	CDK inhibitors	Palbociclib (CDK4 and CDK6 INH)	Phase II (137)	WDLS or DDLS with CDK4 amplification and pRb expression	66% of patients free of PD at 12 weeks	Grade 3–4Anemia Neutropenia Thrombocytopenia

	Mechanism of action	Drugs	Trial (reference)	Study population	Benefits	Common severetoxicities

Apoptosis	PARP inhibitors	Olaparib	Phase II (127)	Recurrent/metastatic adult ES (failure to prior CH), n = 12 patients	NO responses SD: 4 patients, TTP: 5.7 weeks	No significant toxicities

	Heat shock protein inhibitors	Retaspimycin (Hsp-90 INH)	Phase I (128)	Metastatic and/or unresectable STS, n = 54 patients	PR: 2 patients (proof of clinical activity)	Grade 3–4:Fatigue Nausea and vomiting Headache Artharalgia

	Proteaseome inhibitor	Bortezomib	Phase II (129)	Metastatic OS, ES, RMS, and STS with no prior treatment for advanced disease, n = 25 patients	Lack of benefit (trial prematurely closed)	Grade 3–4:Neuropathy Asthenia Myalgias

	MDM2 inhibitor	RG7112	Proof of mechanism study (130)	WDLS or DDLS with MDM2 amplification receive RG7112 prior to surgery, n = 20 patients	SD: 14 patients, IHQ: activation of p53 pathway	Grade 3–4Neutropenia Thrombocytopenia

			P	Phase I trial with extension	Metabolic responses (PET-CT) IHQ: activation of p53 (MDM2-ind	Grade 3–4

			hase I (131)	 cohort for sarcoma patients, n = 30 (sarcoma patients)	ependent)	Cytopenias

	PI3K-AKT-mTOR pathway inhibitors	Ridaforolimus (mTOR INH)	Phase II (132)	Pre-treated advanced bone and STS, n = 212 patients	RR: 1.9%, clinical benefit: 28.8%	Grade 3–4Fatigue Stomatitis Hypertriglyceridemia Anemia Thrombocytopenia

			Phase III (133)	Advanced bone and STS with clinical benefit to previous CH were randomized to maintenance Ridaforolimus or Placebo, n = 711 patients	Improvement in PFS (17.7 weeks with Ridaforolimus vs. 14.6 weeks with Placebo, HR: 0.72, p: 0.001)	Similar to previous study

		Everolimus (mTOR INH)	Phase II (134)	Pre-treated advanced bone and STS, n = 41 patients	Poor clinical activity	Grade 3–4Hyperglicemia Stomatitis Pain Asthenia

	Anti-angiogenic therapy	Sorafenib (VEGFR2, VEGFR3, PDGFR, and c-Kit INH)	Phase II (135)	Pre-treated advanced STS, n = 101 patients	RR: 14.5%, SD: 32.9% (leiomyosarcoma better PFS)	Grade 3–4Fatigue Diarrhea Hand–foot Syndrome Nausea and vomiting

		Pazopanib (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR, and c-Kit INH)	Phase III (136)	Pre-treated non-adipocytic STS randomized to PAZOPANIB vs. PLACEBO, n = 369 patients	Improvement in PFS (4.6 months with PAZOPANIB vs. 1.6 months with Placebo, HR: 0.31, p < 0.0001)	Grade 3–4Asthenia Hypertension Anorexia Alteration of transaminases

Mitotic catastrophe	CDK inhibitors	Palbociclib (CDK4 and CDK6 INH)	Phase II (137)	WDLS or DDLS with CDK4 amplification and pRb expression	66% of patients free of PD at 12 weeks	Grade 3–4Anemia Neutropenia Thrombocytopenia


	Flg22-responsive genes*	Light-responsive genes**	Overlap genes	P-value***

Flg22-induced light-dependent genes	3579	(flg22-up)	2576	(light-dependent)	536	8.790e-24

Flg22-induced light-repressed genes	3579	(flg22-up)	2161	(light-repressed)	239	1.084e-05

Flg22-repressed light-dependent genes	4159	(flg22-down)	2576	(light-dependent)	359	2.599e-04

Flg22-repressed light-repressed genes	4159	(flg22-down)	2161	(light-repressed)	370	0.15

	Flg22-responsive genes*	Light-responsive genes**

Flg22-induced light-dependent genes	3579	(flg22-up)	2576

Flg22-induced light-repressed genes	3579	(flg22-up)	2161

Flg22-repressed light-dependent genes	4159	(flg22-down)	2576

Flg22-repressed light-repressed genes	4159	(flg22-down)	2161

Light-responsive genes**	Overlap genes	P-value***

(light-dependent)	536	8.790e-24

(light-repressed)	239	1.084e-05

(light-dependent)	359	2.599e-04

(light-repressed)	370	0.15


Patient No.	Ethnicity	Biochemical findings	Phenotype	ACADS genotype

C4a	C4/C2a	C4/C3a	C4/C8a	EMAb

1	R	1.53	0.21	1.35	40.38	N/A	microcephaly, DD/ID, marked hypotonus, horizontal nystagmus	c.310_312delGAG/c.310_312delGAG

9	R	N/A	N/A	N/A	N/A	634	DD/ID, apnoic pause, bleeding into the adrenal glands in the neonatal age, hypoglycaemia

10	R	1.44	0.05	0.81	30.64	363	central hypotonus with acral hypertonus, laryngomalatia

12	R	1.07	0.07	1.07	40.75	146	epilepsy, hypotonus, irritability, cerebral palsy, pectus carinatum, kyphoscoliosis

14	R	0.97	0.08	0.61	59.6	1070	recurrent sepsis, MAC, hepatosplenomegaly, severe hepatopathy along with gastroenteritis

15	C	2.77	0.11	3.26	60.23	169	mild MAC in neonatal age, at age 2 yo - DD/ID, hypotonus, at age 3 yo – without DD/ID

17	R	N/A	N/A	N/A	N/A	329	severe DD/ID, parents consanguinity, MAC, brother – DD/ID with no biochemical positivity to SCADD

23	R	1.19	0.07	0.57	129	322	hypoglycaemia, elevated CK

24	R	1.00	0.10	0.53	60.88	N/A	mild MAC

25	R	1.90	0.14	1.98	52.34	657	DD	c.310_312delGAG/c.1138C>T

32	R	N/A	N/A	N/A	N/A	306	prematurity, severe DD/ID, quadruparesis, recurrent hypoglycaemia

33	R	N/A	N/A	N/A	N/A	965	DD/ID(milder than brother - patient No. 32)

35	R	1.52	0.08	0.94	77.08	433	mild hepatomegaly, hyperammonemia, MAC

52	N/A	0.61	0.06	5.28	10.18	N/A	DD/ID c	c.310_312delGAG/c.625G>A

53	R	1.20	0.07	0.72	17.93	135	short stature, ophtalmoplegia (first sign – suspicion for congenital myasthenia), hypomimic facies, severe kyphoscoliosis, DD/ID, cachexia, hypotonus, respiratory failure, diffuse brain edema, coma vigile (high suspicion for other unknown neuromuscular disease)

54	R	N/A	N/A	N/A	N/A	71	epilepsy

55	R	0.44	0.03	0.19	50.42	54	recidivating granulomatous hepatopathy with hepatomegaly, mild hypertonus, mild DD/ID, epilepsy, apnoic pauses

56	R	0.86	0.03	0.41	21.15	110	recurrent seizures

Phenotype	ACADS genotype

microcephaly, DD/ID, marked hypotonus, horizontal nystagmus	c.310_312delGAG/c.310_312delGAG

DD/ID, apnoic pause, bleeding into the adrenal glands in the neonatal age, hypoglycaemia

central hypotonus with acral hypertonus, laryngomalatia

epilepsy, hypotonus, irritability, cerebral palsy, pectus carinatum, kyphoscoliosis

recurrent sepsis, MAC, hepatosplenomegaly, severe hepatopathy along with gastroenteritis

mild MAC in neonatal age, at age 2 yo - DD/ID, hypotonus, at age 3 yo – without DD/ID

severe DD/ID, parents consanguinity, MAC, brother – DD/ID with no biochemical positivity to SCADD

hypoglycaemia, elevated CK

mild MAC

DD	c.310_312delGAG/c.1138C>T

prematurity, severe DD/ID, quadruparesis, recurrent hypoglycaemia

DD/ID(milder than brother - patient No. 32)

mild hepatomegaly, hyperammonemia, MAC

DD/ID c	c.310_312delGAG/c.625G>A

short stature, ophtalmoplegia (first sign – suspicion for congenital myasthenia), hypomimic facies, severe kyphoscoliosis, DD/ID, cachexia, hypotonus, respiratory failure, diffuse brain edema, coma vigile (high suspicion for other unknown neuromuscular disease)

epilepsy

recidivating granulomatous hepatopathy with hepatomegaly, mild hypertonus, mild DD/ID, epilepsy, apnoic pauses

recurrent seizures


		Non-surgical n = 261	Bariatric surgery n = 301	Adjusted for gender/age/BMI

Range	Mean (SD)	Mean (SD)	F	P	ηp2