Single polynomials that correspond to pairs of cyclotomic polynomials with interlacing zeros

of cyclotomic polynomials with interlacing zero

A conjectural extension of hecke's converse theorem

We formulate a precise conjecture that, if true, extends the converse theorem of Hecke without requiring hypotheses on twists by Dirichlet characters or an Euler product. The main idea is to linearize the Euler product, replacing it by twists by Ramanujan sums. We provide evidence for the conjecture, including proofs of some special cases and under various additional hypotheses

Comprehensive screening of eight known causative genes in congenital hypothyroidism with gland-in-situ

Context: lower thyroid-stimulating hormone (TSH) screening cut-offs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically-located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes, or the thyroid-stimulating hormone receptor (TSHR) underlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken.Objective: to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD and TSHR) in CH cases with GIS.Patients, Design and Setting: we screened forty-nine CH cases with GIS from thirty-four ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico.Results: twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (nineteen cases) most commonly involved TG (twelve), TPO (four), DUOX2 (two) and TSHR (one case). Ten cases harboured triallelic (digenic) mutations: TG and TPO (one); SLC26A4 and TPO (three) and DUOX2 and TG (six cases). Novel variants overall included fifteen TG, six TPO, and three DUOX2 mutations. Genetic basis was not ascertained in twenty patients, including fourteen familial cases.Conclusions: the aetiology ofCHwith GIS remains elusive, with only59%attributable to mutations in TSHR or known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TG or TPO mutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (~41%) of unsolved or ambiguous cases suggests novel genetic aetiologies that remain to be elucidated- See more at: http://press.endocrine.org/doi/10.1210/jc.2016-1879#sthash.8M832MqP.dpu

Comprehensive screening of eight known causative genes in congenital hypothyroidism with gland-in-situ

Context: lower thyroid-stimulating hormone (TSH) screening cut-offs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically-located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes, or the thyroid-stimulating hormone receptor (TSHR) underlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken.Objective: to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD and TSHR) in CH cases with GIS.Patients, Design and Setting: we screened forty-nine CH cases with GIS from thirty-four ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico.Results: twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (nineteen cases) most commonly involved TG (twelve), TPO (four), DUOX2 (two) and TSHR (one case). Ten cases harboured triallelic (digenic) mutations: TG and TPO (one); SLC26A4 and TPO (three) and DUOX2 and TG (six cases). Novel variants overall included fifteen TG, six TPO, and three DUOX2 mutations. Genetic basis was not ascertained in twenty patients, including fourteen familial cases.Conclusions: the aetiology ofCHwith GIS remains elusive, with only59%attributable to mutations in TSHR or known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TG or TPO mutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (~41%) of unsolved or ambiguous cases suggests novel genetic aetiologies that remain to be elucidated- See more at: http://press.endocrine.org/doi/10.1210/jc.2016-1879#sthash.8M832MqP.dpu

Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials.

OBJECTIVE: To explore the effect on perinatal outcome of different fetal monitoring strategies for early-onset fetal growth restriction (FGR). METHODS: This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age. RESULTS: Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P < 0.01). The rate of survival without impairment at 2 years was lowest in pregnancies that underwent immediate delivery (70% (95% CI, 61-78%)) or delayed delivery with monitoring by CTG (69% (95% CI, 57-82%)), increased in those monitored using cCTG only in both GRIT (80% (95% CI, 68-91%)) and TRUFFLE (77% (95% CI, 70-84%)), and was highest in pregnancies monitored using cCTG and DV Doppler (84% (95% CI, 80-89%)) (P < 0.01 for trend). CONCLUSIONS: This analysis supports the hypothesis that the optimal method for fetal monitoring in pregnancies complicated by early-onset FGR is a combination of cCTG and DV Doppler assessment. TRIAL REGISTRATION: GRIT ISRCTN41358726 and TRUFFLE ISRCTN56204499. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease