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Copy number variations (CNVs) of the human 16p11.2 locus are associated with several developmental/neurocognitive syndromes. Particularly, deletion and duplication of this genetic interval are found in patients with autism spectrum disorders, intellectual disability and other psychiatric traits. The high gene density associated with the region and the strong phenotypic variability of incomplete penetrance, make the study of the 16p11.2 syndromes extremely complex. To systematically study the effect of 16p11.2 CNVs and identify candidate genes and molecular mechanisms involved in the pathophysiology, mouse models were generated previously and showed learning and memory, and to some extent social deficits. To go further in understanding the social deficits caused by 16p11.2 syndromes, we engineered deletion and duplication of the homologous region to the human 16p11.2 genetic interval in two rat outbred strains, Sprague Dawley (SD) and Long Evans (LE). The 16p11.2 rat models displayed convergent defects in social behavior and in the novel object test in male carriers from both genetic backgrounds. Interestingly major pathways affecting MAPK1 and CUL3 were found altered in the rat 16p11.2 models with additional changes in males compared to females. Altogether, the consequences of the 16p11.2 genetic region dosage on social behavior are now found in three different species: humans, mice and rats. In addition, the rat models pointed to sexual dimorphism with lower severity of phenotypes in rat females compared to male mutants. This phenomenon is also observed in humans. We are convinced that the two rat models will be key to further investigating social behavior and understanding the brain mechanisms and specific brain regions that are key to controlling social behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martin Lorenzo, Muniz Moreno, Atas, Pellen, Nalesso, Raffelsberger, Prevost, Lindner, Birling, Menoret, Tesson, Negroni, Concordet, Anegon and Herault.)

Background: Roux-en-Y gastric bypass (RYGB) is a recommended treatment for type 2 diabetes mellitus (T2DM) in patients with obesity, with superiority over medical therapy. While diabetes remission is achieved initially in 60-90% of patients following surgery, many may experience relapse of diabetes on the long-term. Data on long-term follow-up of bariatric surgery is scarce. We report this 12-year follow-up study of glycaemic control following RYGB., Methods: Two hundred seventeen patients with obesity (109 diabetic, 108 matched nondiabetic) who underwent RYGB between 2000 and 2008 were identified. Data was recorded prospectively for these patients at baseline and 2 years postoperatively. The long-term data was obtained via direct contact with the patients cross-checked with our hospital/national patients' electronic databases., Results: The follow-up rate was 88% (initial age 44 ± 9 years, female 79%). The mean (± SD) percentage total weight loss was 28% (± 15%) and 27% (± 17%) at 2 years and 12 years, respectively. Diabetes remission rate was 69% at 2 years, but decreased to 36% at 12 years following surgery. The 12-year incidence of new-onset T2DM in the control group was 4.3%. On univariate analysis, age, preoperative duration of diabetes and use of insulin were associated with less chance of diabetes remission at long-term (p value 0.06, 0.01 and 0.03, respectively). However, on multivariate regression analysis, only the duration of diabetes preoperatively remained significant (p = 0.025)., Conclusion: This study shows a high relapse of diabetes 12-year post-RYGB despite the durability of weight loss. This affects preoperative counselling and indicates a need for a longer follow-up to detect relapse.

Theoretical predictions with next-to-next-to-leading order (NNLO) QCD accuracy combined with the next-to-leading order (NLO) electroweak (EW) corrections are presented for differential observables of the double-Higgs production process via vector-boson fusion. While the QCD corrections were previously known, the EW ones are computed here for the first time. The numerical results are obtained for a realistic experimental set-up at the LHC and are presented in the form of fiducial cross sections and differential distributions. Within this setup we find that the VBF approximation employed in the NNLO QCD correction is accurate at the sub-percent level. We find that the NLO EW corrections within the fiducial volume are - 6.1 % , making them of almost the same order as the NLO QCD corrections. In some kinematic regions they can grow as large as - 30 % making them the dominant radiative corrections. When the EW corrections are combined with the NNLO QCD corrections we find a total correction of - 14.8 % . The results presented here thus comprise the state-of-the-art theoretical predicition for the double-Higgs production via vector-boson fusion, which will be of value to the high-luminosity programme at the LHC., (© The Author(s) 2020.)

In this article we present an event generator based on the Monte Carlo program Powheg in combination with the matrix-element generator Recola. We apply it to compute NLO electroweak corrections to same-sign W-boson scattering, which have been shown to be large at the LHC. The event generator allows for the generation of unweighted events including the effect of the NLO electroweak corrections matched to a QED parton shower and interfaced to a QCD parton shower. In view of the expected experimental precision of future measurements, the use of such a tool will be indispensable., (© The Author(s) 2019.)

Vector-boson scattering processes are of great importance for the current run-II and future runs of the Large Hadron Collider. The presence of triple and quartic gauge couplings in the process gives access to the gauge sector of the Standard Model (SM) and possible new-physics contributions there. To test any new-physics hypothesis, sound knowledge of the SM contributions is necessary, with a precision which at least matches the experimental uncertainties of existing and forthcoming measurements. In this article we present a detailed study of the vector-boson scattering process with two positively-charged leptons and missing transverse momentum in the final state. In particular, we first carry out a systematic comparison of the various approximations that are usually performed for this kind of process against the complete calculation, at LO and NLO QCD accuracy. Such a study is performed both in the usual fiducial region used by experimental collaborations and in a more inclusive phase space, where the differences among the various approximations lead to more sizeable effects. Afterwards, we turn to predictions matched to parton showers, at LO and NLO: we show that on the one hand, the inclusion of NLO QCD corrections leads to more stable predictions, but on the other hand the details of the matching and of the parton-shower programs cause differences which are considerably larger than those observed at fixed order, even in the experimental fiducial region. We conclude with recommendations for experimental studies of vector-boson scattering processes.

For the first time full next-to-leading-order electroweak corrections to off-shell vector-boson scattering are presented. The computation features the complete matrix elements, including all nonresonant and off-shell contributions, to the electroweak process pp→μ^{+}ν_{μ}e^{+}ν_{e}jj and is fully differential. We find surprisingly large corrections, reaching -16% for the fiducial cross section, as an intrinsic feature of the vector-boson-scattering processes. We elucidate the origin of these large electroweak corrections upon using the double-pole approximation and the effective vector-boson approximation along with leading-logarithmic corrections.

Weakly interacting dark matter particles can be pair-produced at colliders and detected through signatures featuring missing energy in association with either QCD/EW radiation or heavy quarks. In order to constrain the mass and the couplings to standard model particles, accurate and precise predictions for production cross sections and distributions are of prime importance. In this work, we consider various simplified models with s -channel mediators. We implement such models in the FeynRules/MadGraph5_aMC@NLO framework, which allows to include higher-order QCD corrections in realistic simulations and to study their effect systematically. As a first phenomenological application, we present predictions for dark matter production in association with jets and with a top-quark pair at the LHC, at next-to-leading order accuracy in QCD, including matching/merging to parton showers. Our study shows that higher-order QCD corrections to dark matter production via s -channel mediators have a significant impact not only on total production rates, but also on shapes of distributions. We also show that the inclusion of next-to-leading order effects results in a sizeable reduction of the theoretical uncertainties.

Patients with esophageal cancer may present with dysphagia and weight loss. Resectable lesions require consideration of neoadjuvant chemotherapy, which improves survival but have side effects, which compound already poor intake. Prevention of malnutrition has historically required interventions such as surgical jejunostomy or percutaneous endoscopic gastrostomy, which carry associated morbidity. With established roles in palliation, self-expanding removable metal stents (SERMS) may provide an alternative intervention in resectable disease. We sought to evaluate outcomes from our unit's introduction of SERMS in dysphagic patients prior to esophagectomy. All dysphagic patients presenting with esophageal cancer and considered for curative surgery between April 2006 and November 2008 were offered preoperative treatment of dysphagia with SERMS during neoadjuvant chemotherapy. Baseline and preoperative outcomes assessed included dysphagia score and nutritional markers. Sixteen patients underwent esophageal stenting during neoadjuvant therapy of whom 7/16 (44%) were female with mean age 63 (53-76). In 12/16 (75%), tumors were located in the lower one third of the esophagus. There was a significant fall in mean dysphagia score from 2.5 (range 1-4) to 1.1 (range 0-3) immediately preoperatively. There was no significant change in serum albumin, weight, or body mass index. Stent-related morbidity occurred in 4/16 (25%) patients and stomach migration occurred in 7/16 (43.8%). All were resolved endoscopically and there was no stent-related mortality. Of 10/16 (62.5%) patients ultimately progressing to esophagectomy, 30-day mortality was 6.3%. Anastomotic leak occurred in one patient (10%) and R1 resection rate was 20%. SERMS are a safe and effective intervention in dysphagic patients undergoing neoadjuvant chemotherapy for esophageal cancer. Complications are minor and readily treatable with endoscopy. Objective parameters suggest nutritional status is maintained and symptoms are improved. SERMS do not appear to compromise resection., (© 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Introduction: Global Rating Scales (GRS) quantify and structure subjective expert assessment of skill. Hybrid simulators measure performance during physical laparoscopic tasks through instrument motion analysis. We assessed whether motion analysis metrics were as accurate as structured expert opinion by using GRS., Methods: A random sample of 10 consultant laparoscopic surgeons, 10 senior trainees, and 10 novice students were assessed on a Sharp Dissection task. Coded video footage was reviewed by two blinded assessors and scored using a Likert Scale. Correlation with metrics was tested using Spearman's rho. Inter-rater reliability was measured using intraclass correlation coefficient (ICC)., Results: Strongest GRS-Metric correlations were found for Time/Motion/Progress with Time (Spearman's rho 0.88; p < 0.05) and Instrument Handling with Path Length (Spearman's rho 0.8; p < 0.05). Smoothness correlated with Respect for Tissue in Rater 1 (rho 0.68) but not Rater 2 (rho 0.18). Mean GRS showed stronger inter-rater agreement than individual scale components (ICC 0.68). Correlation coefficients with actual experience group were 0.58-0.74 for mean GRS score and 0.67-0.78 for metrics (Spearman's rho, p < 0.05)., Conclusions: Metrics correlate well with GRS assessment, supporting concurrent validity. Metrics predict experience level as accurately as global rating and are construct valid. Hybrid simulators could provide resource-efficient feedback, freeing trainers to concentrate on teaching.

We report on investigations of the interaction of light with nanoscale antennae made from crystalline GaP nanowires (NWs). Using Raman scattering, we have observed strong optical antenna effects which we identify with internal standing wave photon modes of the wire. The antenna effects were probed in individual NWs whose diameters are in the range 40 < d < 300 nm. The data and our calculations show that the nature of the backscattered light is critically dependent on the interplay between a photon confinement effect and bulk Raman scattering. At small diameter, d < 65 nm, the NWs are found to act like a nearly perfect dipole antenna and the bulk Raman selection rules are masked leading to a polarized scattering intensity function I R approximately cos4 theta. Underscoring the importance of this work is the realization that a fundamental understanding of the "optical antenna effect" in semiconducting NWs is essential to the analysis of all electro-optic effects in small diameter filaments.

Problem: A large audit of colonoscopy in the United Kingdom showed that the unadjusted completion rate was 57% when stringent criteria for identifying the caecum were applied. The caecum should be reached 90% of the time. Little information is available on what units or operators need to do to improve to acceptable levels., Design: Quality improvement programme using two completed cycles of audit., Setting: Endoscopy department in a university linked general hospital in northeast England., Key Measures for Improvement: Colonoscopy completion rate., Strategy for Change: Two audit cycles were completed between 1999 and 2002. Changes to practice were based on results of audit and took into account the opinions of relevant staff. Lack of time for each colonoscopy, poor bowel preparation, especially in frail patients, and a mismatch between number of colonoscopies done and completion rate for individual operators were responsible for failed colonoscopies. Appropriate changes were made., Effects of Change: The initial crude colonoscopy completion rate was 60%, improving to 71% after the first round of audit and 88% after the second round, which approximates to the agreed audit standard of 90%. The final adjusted completion rate was 94%., Lessons Learnt: Achievement of the national targets in a UK general hospital is possible by lengthening appointments, admitting frail patients for bowel preparation to one ward, and allocating colonoscopies to the most successful operators.