Are Biologics Safe in the Immediate Postoperative Period? A Single-Center Evaluation of Consecutive Crohn's Surgical Patients.

There is no study to date examining the safety of initiating or restarting biologic therapy after major abdominal surgery for Crohn's disease. The purpose of this study was to determine differences in the rates of 90-day superficial surgical site infections, intra-abdominal sepsis, and overall postoperative infectious complications among patients who were initiated on or restarted a biologic within 90 days postoperatively compared with those who were not. This was a retrospective cohort study. The study was conducted at an IBD referral center. Adult patients with Crohn's disease who received a biologic therapy within 90 days of a major abdominal operation between May 20, 2014, and December 31, 2018, were included. Ninety-day superficial surgical site infection, intra-abdominal sepsis, and overall postoperative infectious complications were measured. A total of 680 patients with Crohn's disease were included: 351 were initiated on biologic therapy within 90 days after surgery and 329 were not. Patients exposed to biologic therapy postoperatively were younger (p < 0.001), had a lower BMI (p = 0.0014), were less often diabetic (p = 0.0011), and were more often exposed preoperatively to biologics (p < 0.0001) and immunomodulators (p < 0.0001) but not corticosteroids (p = 0.8399). Of those exposed postoperatively, nearly all (93.7%) had been on a biologics preoperatively, and most resumed the same biologic (68.0%). The median time to starting biologic therapy postoperatively was 31 days (range, 7-89 d). Postoperative biologic exposure was not associated with an increased risk of superficial surgical site infection (HR = 1.02 (95% CI, 0.95-1.09) per week; p = 0.59), intra-abdominal sepsis (HR = 1.07 (95% CI, 0.99-1.16); p = 0.73), or overall postoperative infectious complications (HR = 1.02 (95% CI, 0.98-1.07); p = 0.338); the overall rates of each at 90 days was 13%, 8%, and 28%. The study was limited by its retrospective design and single-center data. Postoperative initiation or resumption of biologic therapy did not increase 90-day rates of superficial surgical site infection, intra-abdominal sepsis, or total infectious complications after major abdominal surgery for Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B207. ¿SON SEGUROS LOS FÁRMACOS BIOLÓGICOS EN EL POSTOPERATORIO INMEDIATO? UNA EVALUACIÓN DE UN SOLO CENTRO DE PACIENTES QUIRÚRGICOS CONSECUTIVOS CON ENFERMEDAD DE CROHN: No hay ningún estudio hasta la fecha que examine la seguridad de iniciar o reiniciar la terapia biológica después de una cirugía abdominal mayor en enfermedad de Crohn.Determinar las diferencias en las tasas a 90 días de infecciones del sitio quirúrgico superficial, sepsis intraabdominal y complicaciones infecciosas postoperatorias generales entre los pacientes en que se inició o reinició un biológico dentro de los 90 días después de la operación en comparación con aquellos que no lo recibieron.Estudio de cohorte retrospectivo.Centro de referencia de enfermedad inflamatoria intestinal.Pacientes adultos con enfermedad de Crohn que recibieron una terapia biológica dentro de los 90 días de una operación abdominal mayor entre el 20 de mayo de 2014 y el 31 de diciembre de 2018.Infección superficial del sitio quirúrgico, sepsis intraabdominal y complicaciones infecciosas postoperatorias generales a 90 días.Se incluyeron un total de 680 pacientes con enfermedad de Crohn: 351 se iniciaron en terapia biológica dentro de los 90 días posteriores a la cirugía y 329 no. Los pacientes expuestos a terapia biológica después de la operación eran más jóvenes (p <0.001), tenían un índice de masa corporal más bajo (p = 0.0014), eran con menos frecuencia diabéticos (p = 0.0011) y estaban expuestos con mayor frecuencia preoperatoriamente a fármacos biológicos (p <0.0001) e inmunomoduladores (p <0.0001) pero no a corticosteroides (p = 0.8399). De los expuestos postoperatoriamente, casi todos (93.7%) habían estado en terapia biológica en el preoperatorio, y la mayoría reanudó la misma terapia biológica (68%). La mediana de tiempo para comenzar la terapia biológica después de la operación fue de 31 días (rango, 7-89 días). La exposición biológica postoperatoria no se asoció con un mayor riesgo de infección superficial del sitio quirúrgico (HR 1.02 (0.95-1.09) por semana, p = 0.59), sepsis intraabdominal. (HR: 1.07 (0.99-1.16), p = 0.73), o complicaciones infecciosas postoperatorias generales (HR: 1.02, intervalo de confianza del 95% 0.98-1.07, p = 0.338); las tasas generales de cada uno a los 90 días fue del 13%, 8% y 28%.Diseño retrospectivo, y datos de un centro único.El inicio o la reanudación en el postoperatorio de la terapia biológica no aumentaron las tasas a 90 días de infección superficial de sitio quirúrgico, sepsis intraabdominal o complicaciones infecciosas totales después de una cirugía abdominal mayor por enfermedad de Crohn. Consulte el Video Resumen en http://links.lww.com/DCR/B207. (Traducción-Dr Jorge Silva Velazco)

Trends in HIV testing and recording of HIV status in the UK primary care setting: a retrospective cohort study 1995-2005

Objectives: To provide nationally representative data on trends in HIV testing in primary care and to estimate the proportion of diagnosed HIV positive individuals known to general practitioners (GPs). Methods: We undertook a retrospective cohort study between 1995 and 2005 of all general practices contributing data to the UK General Practice Research Database (GPRD), and data on persons accessing HIV care (Survey of Prevalent HIV Infections Diagnosed). We identified all practice-registered patients where an HIV test or HIV positive status is recorded in their general practice records. HIV testing in primary care and prevalence of recorded HIV positive status in primary care were estimated. Results: Despite 11-fold increases in male testing and 19-fold increases in non-pregnant female testing between 1995 and 2005, HIV testing rates remained low in 2005 at 71.3 and 61.2 tests per 100 000 person years for males and females, respectively, peaking at 162.5 and 173.8 per 100 000 person years at 25–34 years of age. Inclusion of antenatal tests yielded a 129-fold increase in women over the 10-year period. In 2005, 50.7% of HIV positive individuals had their diagnosis recorded with a lower proportion in London (41.8%) than outside the capital (60.1%). Conclusion: HIV testing rates in primary care remain low. Normalisation of HIV testing and recording in primary care in antenatal testing has not been accompanied by a step change in wider HIV testing practice. Recording of HIV positive status by GPs remains low and GPs may be unaware of HIV-related morbidity or potential drug interactions

Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database

Objective: To describe the contribution of primary care to the diagnosis and management of sexually transmitted infections in the United Kingdom, 1990-2000, in the context of increasing incidence of infections in genitourinary medicine clinics. Design: Population based study. Setting: UK primary care. Participants: Patients registered in the UK general practice research database. Main outcome measures: Incidence of diagnosed sexually transmitted infections in primary care and estimation of the proportion of major such infections diagnosed in primary care. Results: An estimated 23.0% of chlamydia cases in women but only 5.3% in men were diagnosed and treated in primary care during 1998-2000, along with 49.2% cases of non-specific urethritis and urethral discharge in men and 5.7% cases of gonorrhoea in women and 2.9% in men. Rates of diagnosis in primary care rose substantially in the late 1990s. Conclusions: A substantial and increasing number of sexually transmitted infections are diagnosed and treated in primary care in the United Kingdom, with sex ratios differing from those in genitourinary medicine clinics. Large numbers of men are treated in primary care for presumptive sexually transmitted infections

Resolutions and Characters of Irreducible Representations of the N=2 Superconformal Algebra

We evaluate characters of irreducible representations of the N=2 supersymmetric extension of the Virasoro algebra. We do so by deriving the BGG-resolution of the admissible N=2 representations and also a new 3,5,7...-resolution in terms of twisted massive Verma modules. We analyse how the characters behave under the automorphisms of the algebra, whose most significant part is the spectral flow transformations. The possibility to express the characters in terms of theta functions is determined by their behaviour under the spectral flow. We also derive the identity expressing every $\hat{sl}(2)$ character as a linear combination of spectral-flow transformed N=2 characters; this identity involves a finite number of N=2 characters in the case of unitary representations. Conversely, we find an integral representation for the admissible N=2 characters as contour integrals of admissible $\hat{sl}(2)$ characters.Comment: LaTeX2e: amsart, 34pp. An overall sign error corrected in (4.33) and several consequent formulas, and the presentation streamlined in Sec.4.2.3. References added. To appear in Nucl. Phys.

Runaway Events Dominate the Heavy Tail of Citation Distributions

Statistical distributions with heavy tails are ubiquitous in natural and social phenomena. Since the entries in heavy tail have disproportional significance, the knowledge of its exact shape is very important. Citations of scientific papers form one of the best-known heavy tail distributions. Even in this case there is a considerable debate whether citation distribution follows the log-normal or power-law fit. The goal of our study is to solve this debate by measuring citation distribution for a very large and homogeneous data. We measured citation distribution for 418,438 Physics papers published in 1980-1989 and cited by 2008. While the log-normal fit deviates too strong from the data, the discrete power-law function with the exponent $\gamma=3.15$ does better and fits 99.955% of the data. However, the extreme tail of the distribution deviates upward even from the power-law fit and exhibits a dramatic "runaway" behavior. The onset of the runaway regime is revealed macroscopically as the paper garners 1000-1500 citations, however the microscopic measurements of autocorrelation in citation rates are able to predict this behavior in advance.Comment: 6 pages, 5 Figure

Discrete Gauge Symmetries in Discrete MSSM-like Orientifolds

Motivated by the necessity of discrete Z_N symmetries in the MSSM to insure baryon stability, we study the origin of discrete gauge symmetries from open string sector U(1)'s in orientifolds based on rational conformal field theory. By means of an explicit construction, we find an integral basis for the couplings of axions and U(1) factors for all simple current MIPFs and orientifolds of all 168 Gepner models, a total of 32990 distinct cases. We discuss how the presence of discrete symmetries surviving as a subgroup of broken U(1)'s can be derived using this basis. We apply this procedure to models with MSSM chiral spectrum, concretely to all known U(3)xU(2)xU(1)xU(1) and U(3)xSp(2)xU(1)xU(1) configurations with chiral bi-fundamentals, but no chiral tensors, as well as some SU(5) GUT models. We find examples of models with Z_2 (R-parity) and Z_3 symmetries that forbid certain B and/or L violating MSSM couplings. Their presence is however relatively rare, at the level of a few percent of all cases.Comment: 47 pages. References adde

Does the inclusion of protease inhibitors in the insemination extender affect rabbit reproductive performance?

[EN] The bioavailability of buserelin acetate when added to the seminal dose appears to be determined by the activity of the existing aminopeptidases. Thus, the addition of amino peptidase inhibitors to rabbit semen extenders could be a solution to decrease the hormone degradation. This study was conducted to evaluate the effect of the protease activity inhibition on rabbit semen quality parameters and reproductive performance after artificial insemination. Seminal quality was not affected by the incubation with protease inhibitors, being the values of motility, viability, and acrosome integrity not significantly different between the protease inhibitors and the control group. In addition, seminal plasma aminopeptidase activity was inhibited in a 55.1% by the protease inhibitors. On the other hand, regarding the effect of protease inhibitors on reproductive performance, our results showed that the presence of protease inhibitors affected the prolificacy rate (9.2 +/- 0.26 and 9.3 +/- 0.23 vs. 8.2 +/- 0.22 total born per litter for negative control, positive control, and aminopeptidase inhibitors group, respectively; P < 0.05), having this group one kit less per delivery. We conclude that the addition of a wide variety of protease inhibitors in the rabbit semen extender negatively affects prolificacy rate. Therefore, the development of new extenders with specific aminopeptidase inhibitors would be one of the strategies to increase the bioavailability of GnRH analogues without affecting the litter size. (C) 2016 Elsevier Inc. All rights reserved.This research was supported in part by the RTA2013-00058-00-00 from INIA, the European Social Fund and the European FEDER Funds. L Casares-Crespo is supported by a scholarship from Institute Valenciano de Investigaciones Agrarias (IVIA) and the European Social Fund.Casares-Crespo, L.; Vicente Antón, JS.; Talavan, A.; Viudes De Castro, MP. (2016). Does the inclusion of protease inhibitors in the insemination extender affect rabbit reproductive performance?. Theriogenology. 85(5):928-932. doi:10.1016/j.theriogenology.2015.10.044S92893285

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

Background: Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. Methods: Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. Results: Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. Conclusions: These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs

Proficiency Testing of Metagenomics-Based Detection of Food-Borne Pathogens Using a Complex Artificial Sequencing Dataset

Metagenomics-based high-throughput sequencing (HTS) enables comprehensive detection of all species comprised in a sample with a single assay and is becoming a standard method for outbreak investigation. However, unlike real-time PCR or serological assays, HTS datasets generated for pathogen detection do not easily provide yes/no answers. Rather, results of the taxonomic read assignment need to be assessed by trained personnel to gain information thereof. Proficiency tests are important instruments of validation, harmonization, and standardization. Within the European Union funded project COMPARE [COllaborative Management Platform for detection and Analyses of (Re-) emerging and foodborne outbreaks in Europe], we conducted a proficiency test to scrutinize the ability to assess diagnostic metagenomics data. An artificial dataset resembling shotgun sequencing of RNA from a sample of contaminated trout was provided to 12 participants with the request to provide a table with per-read taxonomic assignments at species level and a report with a summary and assessment of their findings, considering different categories like pathogen, background, or contaminations. Analysis of the read assignment tables showed that the software used reliably classified the reads taxonomically overall. However, usage of incomplete reference databases or inappropriate data pre-processing caused difficulties. From the combination of the participants\u2019 reports with their read assignments, we conclude that, although most species were detected, a number of important taxa were not or not correctly categorized. This implies that knowledge of and awareness for potentially dangerous species and contaminations need to be improved, hence, capacity building for the interpretation of diagnostic metagenomics datasets is necessary