Template MRI scans reliably approximate individual and group-level tES and TMS electric fields induced in motor and prefrontal circuits

BackgroundElectric field (E-field) modeling is a valuable method of elucidating the cortical target engagement from transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), but it is typically dependent on individual MRI scans. In this study, we systematically tested whether E-field models in template MNI-152 and Ernie scans can reliably approximate group-level E-fields induced in N = 195 individuals across 5 diagnoses (healthy, alcohol use disorder, tobacco use disorder, anxiety, depression).MethodsWe computed 788 E-field models using the CHARM–SimNIBS 4.0.0 pipeline with 4 E-field models per participant (motor and prefrontal targets for TMS and tES). We additionally calculated permutation analyses to determine the point of stability of E-fields to assess whether the 152 brains represented in the MNI-152 template is sufficient.ResultsGroup-level E-fields did not significantly differ between the individual vs. MNI-152 template and Ernie scans for any stimulation modality or location (p > 0.05). However, TMS-induced E-field magnitudes significantly varied by diagnosis; individuals with generalized anxiety had significantly higher prefrontal and motor E-field magnitudes than healthy controls and those with alcohol use disorder and depression (p < 0.001). The point of stability for group-level E-field magnitudes ranged from 42 (motor tES) to 52 participants (prefrontal TMS).ConclusionMNI-152 and Ernie models reliably estimate group-average TMS and tES-induced E-fields transdiagnostically. The MNI-152 template includes sufficient scans to control for interindividual anatomical differences (i.e., above the point of stability). Taken together, using the MNI-152 and Ernie brains to approximate group-level E-fields is a valid and reliable approach

Estrogen Receptor-1 Genetic Polymorphisms for the Risk of Premature Ovarian Failure and Early Menopause

Background: The aim of this study was to investigate the role of the estrogen receptor 1 (ESR1) genetic polymorphisms for early menopause that was classified as premature ovarian failure (POF) and early menopause (EM) and to examine whether the associations of ESR1 genetic variants are different for POF and EM. Methods: We selected 100 POF cases and matched 100 EM cases and 200 normal menopause (NM) controls from the Korean Multi-Center Cohort. Among them, we restricted idiopathic POF and EM cases vs NM controls by excluding POF/EM cases with medical/surgical causes. The XbaI (rs9340799) and PvuII (rs2234693) in the ESR1 gene were genotyped. The single-nucleotide polymorphism (SNP) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis. Also nominal polytomous logistic regression was used to find whether ESR1 genetic variants are differently associated with POF and EM. Results: The global p values for idiopathic POF and EM were 0.08 and 0.39 (SNP-based), and <0.001 and 0.12 (haplotype-based), respectively. The XbaI genetic variant containing the X allele was marginally significantly associated with a reduced risk of idiopathic POF (OR=0.6, 95% CI 0.3-1.0). The P-x haplotype and diplotypes significantly decreased the risk of idiopathic POF (OR=0.5, 95% CI 0.2-0.9; OR 0.4, 95% CI 0.2-0.9, respectively). In contrast from POF, the P-x haplotypes and diplotypes insignificantly increased the risk for both idiopathic EM (p(polytomous)=0.009 for P-x haplotype; p(polytomous)=0.02 for P-x diplotypes). Conclusion: Our results suggest that the ESR1 gene including PvuII and XbaI polymorphisms may modify the risk of idiopathic premature ovarian failure (POF) but not idiopathic early menopause (EM) risk.Bretherick KL, 2008, FERTIL STERIL, V89, P318, DOI 10.1016/j.fertnstert.2007.03.008Chang SH, 2007, MATURITAS, V58, P19, DOI 10.1016/j.maturitas.2007.04.001Kitamura I, 2007, BONE, V40, P1623, DOI 10.1016/j.bone.2007.02.016Molvarec A, 2007, HYPERTENS RES, V30, P205Hsieh YY, 2007, MOL HUM REPROD, V13, P117, DOI 10.1093/molehr/gal099Dvornyk V, 2006, MATURITAS, V54, P19, DOI 10.1016/j.maturitas.2005.08.005Onland-Moret NC, 2005, CANCER CAUSE CONTROL, V16, P1195, DOI 10.1007/s10552-005-0307-5Popat RA, 2005, NEUROLOGY, V65, P383Schuit SCE, 2005, EUR J ENDOCRINOL, V153, P327, DOI 10.1530/eje.1.01973Kok HS, 2005, HUM REPROD, V20, P536, DOI 10.1093/humrep/deh600Ioannidis JPA, 2004, JAMA-J AM MED ASSOC, V292, P2105van der Klift M, 2004, J BONE MINER RES, V19, P1172, DOI 10.1359/JBMR.040215Schuit SCE, 2004, JAMA-J AM MED ASSOC, V291, P2969Wasserman L, 2004, INT J OBESITY, V28, P49, DOI 10.1038/sj.ijo.0802481van Meurs JBJ, 2003, HUM MOL GENET, V12, P1745, DOI 10.1093/hmg/ddg176Gorai I, 2003, J CLIN ENDOCR METAB, V88, P799, DOI 10.1210/jc.2002-020353Laml T, 2002, HUM REPROD UPDATE, V8, P483Herrington DM, 2002, CIRCULATION, V105, P1879, DOI 10.1161/01.CIR.0000016173.98826.88Kobayashi N, 2002, MATURITAS, V41, P193YOO KY, 2002, ASIAN PAC J CANCER P, V3, P85de Bruin JP, 2001, HUM REPROD, V16, P2014Pelletier G, 2000, J CLIN ENDOCR METAB, V85, P4835Weiderpass E, 2000, CARCINOGENESIS, V21, P623Yan G, 2000, J WOMEN HEALTH GEN-B, V9, P275Lorentzon M, 1999, J CLIN ENDOCR METAB, V84, P4597Weel AEAM, 1999, J CLIN ENDOCR METAB, V84, P3146Drummond AE, 1999, MOL CELL ENDOCRINOL, V151, P57, DOI 10.1016/S0303-7207(99)00038-6Christin-Maitre S, 1998, MOL CELL ENDOCRINOL, V145, P75Torgerson DJ, 1997, EUR J OBSTET GYN R B, V74, P63vanderSchouw YT, 1996, LANCET, V347, P714Kobayashi S, 1996, J BONE MINER RES, V11, P306NELSON LM, 1996, REPROD ENDOCRINOLOGY, P1394KAPRIO J, 1995, HUM BIOL, V67, P739CRAMER DW, 1995, FERTIL STERIL, V64, P740EXCOFFIER L, 1995, MOL BIOL EVOL, V12, P921NELSON LM, 1994, J CLIN ENDOCR METAB, V79, P1470CAPLAN GA, 1994, J ROY SOC MED, V87, P200PALMER JR, 1992, AM J EPIDEMIOL, V136, P408BAGUR AC, 1992, CALCIFIED TISSUE INT, V51, P4FRANCESCHI S, 1991, INT J CANCER, V49, P57MEYER JM, 1991, AM J MED GENET, V39, P148TRELOAR SA, 1990, AM J HUM GENET, V47, P137SNOWDON DA, 1989, AM J PUBLIC HEALTH, V79, P709

Spin effects in the antler event topology at hadron colliders

We investigate spin correlation effects in the "antler" event topology pp-> A-> B1, B2 -> l^{-}, C1, l^{+}, C2 at the LHC. We study the shapes of several kinematic variables, including the relative pseudorapidity, relative azimuthal angle and the energies of the two leptons, as well as several mass variables M_{ll}, Meff, \sqrt{s}_{min}, MT2, MCT and MCTx. We focus on the two kinematic extremes of \sqrt{s} - threshold and infinity - and derive analytical expressions for the differential distributions of several variables, most notably the cos{\theta_{ll}}^* variable proposed by Barr in hep-ph/0511115. For all possible spin assignments of particles A, B and C, we derive the cos{\theta_{ll}}^* differential distribution at threshold, including the effects of spin correlations. Our analytical results help identify the problematic cases for spin discrimination.Comment: 43 pages, 14 figures, Preprint typeset in JHEP styl

The role of TNF genetic variants and the interaction with cigarette smoking for gastric cancer risk: a nested case-control study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the role of <it>TNF </it>genetic variants and the combined effect between <it>TNF </it>gene and cigarette smoking in the development of gastric cancer in the Korean population.</p> <p>Methods</p> <p>We selected 84 incident gastric cancer cases and 336 matched controls nested within the Korean Multi-Center Cancer Cohort. Six SNPs on the <it>TNF </it>gene, <it>TNF</it>-α-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C, and <it>TNF</it>-β 252 A/G were genotyped. The ORs (95% CIs) were calculated using unconditional logistic regression model to detect each SNP and haplotype-pair effects for gastric cancer. The combined effects between the <it>TNF </it>gene and smoking on gastric cancer risk were also evaluated. Multi dimensionality reduction (MDR) analyses were performed to explore the potential <it>TNF </it>gene-gene interactions.</p> <p>Results</p> <p><it>TNF</it>-α-857 C/T containing the T allele was significantly associated with an increased risk of gastric cancer and a linear trend effect was observed in the additive model (OR = 1.6, 95% CI 1.0–2.5 for CT genotype; OR = 2.6, 95% CI 1.0–6.4 for TT genotype). All haplotype-pairs that contained TCT or CCC of <it>TNF</it>-α-1031 T/C, <it>TNF</it>-α-863 C/A, and <it>TNF</it>-α-857 C/T were associated with a significantly higher risk for gastric cancer only among smokers. In the MDR analysis, regardless of smoking status, <it>TNF</it>-α-857 C/T was included in the first list of SNPs with a significant main effect.</p> <p>Conclusion</p> <p><it>TNF</it>-α-857 C/T polymorphism may play an independent role in gastric carcinogenesis and the risk for gastric cancer by <it>TNF </it>genetic effect is pronounced by cigarette smoking.</p

Oncogenic CagA Promotes Gastric Cancer Risk via Activating ERK Signaling Pathways: A Nested Case-Control Study

Background: CagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer. Methods: In the discovery phase, a total of 580 SNPs within +/-5 kbp of 30 candidate genes were genotyped to examine an association with gastric cancer risk in the Korean Multi-center Cancer Cohort (100 incident gastric cancer case-control sets). The most significant SNPs (raw or permutated p value??0.02) identified in the discovery analysis were re-evaluated in the extension phase using unconditional logistic regression model (400 gastric cancer case-control sets). Combined analyses including pooled-and meta-analysis were conducted to summarize all the results. Results: 24 SNPs in eight genes (ERK, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk) were significantly associated with gastric cancer risk in the individual SNP analyses in the discovery phase (p??0.05). In the extension analyses, ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 showed marginally significant gene-dose effects for gastric cancer. Consistently, final combined analysis presented the SNPs as significantly associated with gastric cancer risk (OR = 1.56, [95% CI: 1.19-2.06], OR = 0.61, [95% CI: 0.43-0.87], OR = 0.59, [95% CI: 0.54-0.76], respectively). Conclusions: Our findings suggest that ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 are genetic determinants in gastric carcinogenesis

Genetic Susceptibility on CagA-Interacting Molecules and Gene-Environment Interaction with Phytoestrogens: A Putative Risk Factor for Gastric Cancer

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk

Acyclovir for treating varicella in otherwise healthy children and adolescents: a systematic review of randomised controlled trials

BACKGROUND: Acyclovir has the potential to shorten the course of chickenpox which may result in reduced costs and morbidity. We conducted a systematic review of randomised controlled trials that evaluated acyclovir for the treatment of chickenpox in otherwise healthy children. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched. The reference lists of relevant articles were examined and primary authors and Glaxo Wellcome were contacted to identify additional trials. Two reviewers independently screened studies for inclusion, assessed study quality using the Jadad scale and allocation concealment, and extracted data. Continuous data were converted to a weighted mean difference (WMD). Overall estimates were not calculated due to differences in the age groups studied. RESULTS: Three studies were included. Methodological quality was 3 (n = 2) and 4 (n = 1) on the Jadad scale. Acyclovir was associated with a significant reduction in the number of days with fever, from -1.0 (95% CI -1.5,-0.5) to -1.3 (95% CI -2.0,-0.6). Results were inconsistent with respect to the number of days to no new lesions, the maximum number of lesions and relief of pruritis. There were no clinically important differences between acyclovir and placebo with respect to complications or adverse effects. CONCLUSION: Acyclovir appears to be effective in reducing the number of days with fever among otherwise healthy children with chickenpox. The results were inconsistent with respect to the number of days to no new lesions, the maximum number of lesions and the relief of itchiness. The clinical importance of acyclovir treatment in otherwise healthy children remains controversial

Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin