bluuebunny/crossref_metadata_2025 huggingface dataset:
Uniting Evidence-Based Evaluation with the ACGME Plastic Surgery Milestones: A Simple and Reliable Assessment of Resident Operative Performance
Authors: Kobraei Edward M. , Bohnen Jordan D. , George Brian C. , Mullen John T. , Lillemoe Keith D. , Austen William G. , Liao Eric C.
Published: April 2016

Background:

Milestones evaluations in plastic surgery reflect a shift toward competency-based training but have created a number of challenges. The authors have incorporated the smartphone application evaluation tool, System for Improving and Measuring Procedural Learning (SIMPL), that was recently developed by a multi-institutional research collaborative. In this pilot study, the authors hypothesize that SIMPL can improve resident evaluation and also collect granular performance data to simplify compliance with the plastic surgery Milestones.

Methods:

SIMPL was prospectively piloted with a plastic surgery resident and faculty surgeon at Massachusetts General Hospital in this institutional review board–approved study. The study period was a 2-month interval corresponding to the resident’s rotation.

Results:

The resident-faculty combination performed 20 cases together. All cases were evaluated with SIMPL. SIMPL evaluations uniformly took under 1 minute to submit. The average time to completed evaluation from surgery completion was 5 hours (<0.5 hour to 12 hours). Concrete, objective, and specific data about resident performance were collected for every case and presented in a concise format.

Conclusions:

SIMPL is an innovative, evidence-based evaluation system that makes performance assessment feasible for every procedure in which a plastic surgery resident participates. SIMPL’s competency-based framework can be easily scaled to facilitate data collection and reporting of mandatory Milestones evaluations at the program and national levels. This technology will support a shared vocabulary between residents and faculty to enhance intraoperative education.
Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships
Authors: Lyte Mark , Fodor Anthony A. , Chapman Clinton D. , Martin Gary G. , Perez-Chanona Ernesto , Jobin Christian , Dess Nancy K.
Published: April 2016

Objectives

The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress.

Methods

Occidental low and high-saccharin–consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition.

Results

The saccharin phenotype was confirmed (low-saccharin–consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin–consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate.

Discussion

The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.
Interactions Between Depression and Lower Urinary Tract Symptoms: The Role of Adverse Life Events and Inflammatory Mechanisms. Results From the European Male Ageing Study
Authors: Castellini Giovanni , Wu Frederick C.W. , Finn Joseph D. , O'Neill Terrence W. , Lean Michael E.J. , Pendleton Neil , Rastrelli Giulia , Rutter Martin K. , Gacci Mauro , Ricca Valdo , Maggi Mario
Published: April 2016

Objectives

Depression and lower urinary tract symptoms (LUTSs) have been found to co-occur among aging men. The present study attempted to clarify the nature of this relationship, considering adverse life events as potential moderators and the inflammation as an underlying biological mechanism.

Methods

The relationship between depression and LUTS was evaluated using data from the European Male Ageing Study, the largest multicenter population-based study of aging in European men. The sample included 3369 men who were assessed by means of several self-reported questionnaires, including the Beck Depression Inventory-II, the International Prostate Symptom Score, and the Adverse Life Events Scale. Participants were asked to provide information regarding general health and life-style, and medical comorbidities. Biological measures including prostate-specific antigen, testosterone, and C-reactive protein were measured.

Results

LUTS and depressive symptoms were correlated (R
2 = 0.32, β = .10, p < .001), even after adjusting for life-style, psychological, and medical variables. A history of adverse life events was associated with both higher LUTS and Beck Depression Inventory scores. Furthermore, adverse life events moderated the LUTS-depression association (F = 22.62, b = 0.061, p < .001), which increased as a function of the number of life events. C-reactive protein was found to mediate the LUTS-depression association. This mediation effect was moderated by number of adverse life events.

Conclusions

Participants with a history of adverse life events represent a vulnerable population in whom the association between somatic and depressive symptoms is stronger. One of the biological mechanisms underlying this association could be an activation of the central inflammatory signaling pathways.
Brief Report: Rethinking Data Collection for HIV Prevention Trials
Authors: Harel Ofer , Nazzaro Valerie
Published: April 2016

There is a strong push to conduct large-scale randomized controlled study designs in HIV prevention studies. In these randomized controlled studies, the primary research objective is typically to determine the treatment effect based on some biological outcome (eg, HIV infection). But many unused self-reported outcomes are also being collected. We illustrate the extent of this problem using the EXPLORE data as an example.
High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department
Authors: Jacobson Kathleen R. , Arora Sanjay , Walsh Kristin B. , Lora Meredith , Merjavy Stephen , Livermore Shanna , Menchine Michael
Published: April 2016

Earlier intervention in acute HIV infection limits HIV reservoirs and may decrease HIV transmission. We developed criteria for empiric antiretroviral therapy (ART) in an emergency department (ED) routine HIV screening program. We assessed the feasibility and willingness of patients with suspected acute HIV infection in the ED to begin ART. A suspected acute HIV infection was defined as a positive HIV antigen antibody combination immunoassay with pending HIV-antibody differentiation test results and HIV RNA viral load. During the study period, there were 16 confirmed cases of acute HIV infection: 11 met our criteria for empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED against medical advice without a prescription for ART. Eight patients completed at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well received by patients, and offers a unique entry point into the HIV care continuum.
Timing of Antiretroviral Treatment, Immunovirologic Status, and TB Risk: Implications for Testing and Treatment
Authors: Pettit April C. , Mendes Adell , Jenkins Cathy , Napravnik Sonia , Freeman Aimee , Shepherd Bryan E. , Dowdy David , Gill John , Rachlis Anita , Moore Richard , Sterling Timothy R. ,   for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) investigators of International epidemiologic Databases to Evaluate AIDS (IeDEA)
Published: April 2016

Background:

Tuberculosis (TB) risk and mortality increase in the 6 months after highly active antiretroviral therapy (HAART) initiation. This short-term risk may be a consequence of HAART initiation and immune reconstitution. Alternatively, it may be due to confounding by low CD4+ counts and high HIV viral loads (VLs). We assessed the TB risk before and after HAART initiation while appropriately controlling for time-updated laboratory values and HAART exposure.

Methods:

We conducted an observational cohort study among persons enrolled in the North American AIDS Cohort Collaboration on Research and Design from 1998 through 2011. A marginal structural model was constructed to estimate the association of HAART initiation and TB risk. Inverse probability weights for the probability of HAART initiation were incorporated.

Results:

Among 26,342 patients, 94 cases of TB were diagnosed during 147,557 person-years (p-y) of follow-up. The unadjusted TB rates were 93/100,000 p-y [95% confidence interval (CI): 63 to 132] before HAART initiation, 203/100,000 p-y (95% CI: 126 to 311) ≤6 months after HAART initiation, and 40/100,000 p-y (95% CI: 29 to 55) >6 months on HAART. After controlling for time-updated laboratory values, the adjusted odds of TB ≤6 months after HAART initiation and >6 months was 0.65 (95% CI: 0.28 to 1.51) and 0.29 (95% CI: 0.16 to 0.53), respectively.

Conclusions:

TB risk in the first 6 months after HAART initiation is not higher than that before HAART initiation after adjusting for CD4+ count and VLs. These findings suggest that short-term TB risk may be related to low CD4+ counts and high VLs near HAART initiation and support early HAART initiation to decrease TB risk.
HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy
Authors: Mujugira Andrew , Celum Connie , Coombs Robert W. , Campbell James D. , Ndase Patrick , Ronald Allan , Were Edwin , Bukusi Elizabeth A. , Mugo Nelly , Kiarie James , Baeten Jared M. ,   for the Partners PrEP Study Team
Published: April 2016

Objective:

Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. We sought to determine HIV transmission risk prior to achieving complete viral suppression.

Design:

Prospective cohort study.

Methods:

Using data from the Partners PrEP Study, a prospective study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, we examined multiple markers of HIV transmission risk during the first months after ART initiation: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and generalized estimating equations logistic regression.

Results:

The cumulative probabilities of achieving blood viral suppression (<80 copies per milliliter) 3, 6, and 9 months after ART initiation were 65.3%, 84.8%, and 89.1%, respectively. Endocervical and seminal HIV RNA were detectable in 12% and 21% of samples obtained within 6 months of ART. Pregnancy incidence was 8.8 per 100 person-years during the first 6 months of ART, and sex unprotected by condoms was reported at 10.5% of visits. Among initially uninfected partners, HIV incidence before ART was 2.08 per 100 person-years (55 infections; 2644 person-years), 1.79 for 0–6 months after ART initiation (3 infections; 168 person-years), and 0.00 with >6 months of ART (0 infections; 167 person-years).

Conclusions:

Residual HIV transmission risk persists during the first 6 months of ART, with incomplete viral suppression in blood and genital compartments. For HIV-serodiscordant couples in which the infected partner starts ART, other prevention options are needed, such as pre-exposure prophylaxis, until viral suppression is achieved.
Complications and Route of Delivery in a Large Cohort Study of HIV-1–Infected Women—IMPAACT P1025
Authors: Livingston Elizabeth G. , Huo Yanling , Patel Kunjal , Tuomala Ruth E. , Scott Gwendolyn B. , Stek Alice ,   for the P1025 Team of the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group
Published: April 2016

Objective:

To investigate complications of cesarean section in a cohort of HIV-infected pregnant women.

Methods:

IMPAACT P1025 is a prospective cohort study of HIV-1–infected women and infants, enrolled 2002–2013, at clinical sites in the United States and Puerto Rico. Demographic, medical, and obstetric data were collected and analyzed including cesarean indications. The delivery route was categorized as elective cesarean (ECS) (before labor and <5 minutes before membrane rupture), nonelective cesarean (NECS) (all other cesareans) or vaginal delivery. Logistic regression models evaluated associations between delivery route and maternal intrapartum/postpartum morbidities. Composite morbidity of vaginal delivery was compared with ECS and NECS.

Results:

This study included 2297 women. Of note, 99% used antiretroviral medication and 89% were on a combination antiretroviral therapy regimen; 84% had a HIV-1 viral load ≤400 copies per milliliter before delivery; 46% (1055) delivered vaginally, 35% (798) by ECS, and 19% (444) by NECS. Although interruption of HIV-1 infection was the second most frequent indication for cesarean after repeat cesarean, it decreased as an indication over time. There were no delivery-related maternal mortalities. Overall, 19% of women had ≥1 complication(s)—primarily wound complications (14%) or other infections (11%). Vaginal delivery had the lowest complication rate (13%), followed by ECS (23%), and highest NECS (28%) with an overall P < 0.001. HIV-1 mother-to-child transmission rates were low and did not differ by delivery mode group.

Conclusions:

HIV interruption as cesarean indicator declined during the study. Morbidity was more common in HIV-infected women delivering by NECS than ECS and lowest with vaginal delivery.

Clinical Trial Registration:

Prenatal and Postnatal Studies of Interventions for Prevention of Mother-To-Child Transmission https://clinicaltrials.gov/ct2/show/NCT00028145?term=impaact+1025&rank=2 NCT00028145.
Implementation and Operational Research: Impact of a Systems Engineering Intervention on PMTCT Service Delivery in Côte d'Ivoire, Kenya, Mozambique: A Cluster Randomized Trial
Authors: Rustagi Alison Silvis , Gimbel Sarah , Nduati Ruth , Cuembelo Maria de Fatima , Wasserheit Judith N. , Farquhar Carey , Gloyd Stephen , Sherr Kenneth ,   with input from the SAIA Study Team
Published: April 2016

Background:

Efficacious interventions to prevent mother-to-child HIV transmission (PMTCT) have not translated well into effective programs. Previous studies of systems engineering applications to PMTCT lacked comparison groups or randomization.

Methods:

Thirty-six health facilities in Côte d'Ivoire, Kenya, and Mozambique were randomized to usual care or a systems engineering intervention, stratified by country and volume. The intervention guided facility staff to iteratively identify and then rectify barriers to PMTCT implementation. Registry data quantified coverage of HIV testing during first antenatal care visit, antiretrovirals (ARVs) for HIV-positive pregnant women, and screening HIV-exposed infants (HEI) for HIV by 6–8 weeks. We compared the change between baseline (January 2013–January 2014) and postintervention (January 2015–March 2015) periods using t-tests. All analyses were intent-to-treat.

Results:

ARV coverage increased 3-fold [+13.3% points (95% CI: 0.5 to 26.0) in intervention vs. +4.1 (−12.6 to 20.7) in control facilities] and HEI screening increased 17-fold [+11.6 (−2.6 to 25.7) in intervention vs. +0.7 (−12.9 to 14.4) in control facilities]. In prespecified subgroup analyses, ARV coverage increased significantly in Kenya [+20.9 (−3.1 to 44.9) in intervention vs. −21.2 (−52.7 to 10.4) in controls; P = 0.02]. HEI screening increased significantly in Mozambique [+23.1 (10.3 to 35.8) in intervention vs. +3.7 (−13.1 to 20.6) in controls; P = 0.04]. HIV testing did not differ significantly between arms.

Conclusions:

In this first randomized trial of systems engineering to improve PMTCT, we saw substantially larger improvements in ARV coverage and HEI screening in intervention facilities compared with controls, which were significant in prespecified subgroups. Systems engineering could strengthen PMTCT service delivery and protect infants from HIV.
Morphology of the Aging Lung on Computed Tomography
Authors: Copley Susan J.
Published: April 2016

As the population becomes older, recognition of the pulmonary computed tomography (CT) features of “normal” aging is likely to become increasingly important to differentiate from clinically significant disease. Several studies have evaluated the appearances of the lung parenchyma and large and small airways in asymptomatic older individuals and found increased prevalence of cysts, reticular pattern, air trapping, bronchial dilation, and bronchial wall thickening in older individuals compared with younger individuals. Objective differences in CT lung parenchymal attenuation and complexity have also been described. The CT appearances of the aging lung are illustrated, and the histopathologic and functional changes are discussed.
Contributions of the Musculus Uvulae to Velopharyngeal Closure Quantified With a 3-Dimensional Multimuscle Computational Model
Authors: Inouye Joshua M. , Lin Kant Y. , Perry Jamie L. , Blemker Silvia S.
Published: April 2016

The convexity of the dorsal surface of the velum is critical for normal velopharyngeal (VP) function and is largely attributed to the levator veli palatini (LVP) and musculus uvulae (MU). Studies have correlated a concave or flat nasal velar surface to symptoms of VP dysfunction including hypernasality and nasal air emission. In the context of surgical repair of cleft palates, the MU has been given relatively little attention in the literature compared with the larger LVP. A greater understanding of the mechanics of the MU will provide insight into understanding the influence of a dysmorphic MU, as seen in cleft palate, as it relates to VP function. The purpose of this study was to quantify the contributions of the MU to VP closure in a computational model. We created a novel 3-dimensional (3D) finite element model of the VP mechanism from magnetic resonance imaging data collected from an individual with healthy noncleft VP anatomy. The model components included the velum, posterior pharyngeal wall (PPW), LVP, and MU. Simulations were based on the muscle and soft tissue mechanical properties from the literature. We found that, similar to previous hypotheses, the MU acts as (i) a space-occupying structure and (ii) a velar extensor. As a space-occupying structure, the MU helps to nearly triple the midline VP contact length. As a velar extensor, the MU acting alone without the LVP decreases the VP distance 62%. Furthermore, activation of the MU decreases the LVP activation required for closure almost 3-fold, from 20% (without MU) to 8% (with MU). Our study suggests that any possible salvaging and anatomical reconstruction of viable MU tissue in a cleft patient may improve VP closure due to its mechanical function. In the absence or dysfunction of MU tissue, implantation of autologous or engineered tissues at the velar midline, as a possible substitute for the MU, may produce a geometric convexity more favorable to VP closure. In the future, more complex models will provide further insight into optimal surgical reconstruction of the VP musculature in normal and cleft palate populations.
Simulation-Based Assessment of ECMO Clinical Specialists
Authors: Fehr James J. , Shepard Mark , McBride Mary E. , Mehegan Mary , Reddy Kavya , Murray David J. , Boulet John R.
Published: April 2016

Objective

The aims of the study were (1) to create multiple scenarios that simulate a range of urgent and emergent extracorporeal membrane oxygenation (ECMO) events and (2) to determine whether these scenarios can provide reliable and valid measures of a specialist’s advanced skill in managing ECMO emergencies.

Design

Multiscenario simulation-based performance assessment was performed.

Setting

The study was conducted in the Saigh Pediatric Simulation Center at St. Louis Children’s Hospital.

Subjects

ECMO clinical specialists participated in the study.

Measurements and Main Results

Twenty-five ECMO specialists completed 8 scenarios presenting acute events in simulated ECMO patients. Participants were evaluated by 2 separate reviewers for completion of key actions and for global performance. The scores were highest for the hemodilution scenario, whereas the air entrainment scenario had the lowest scores. Psychometric analysis demonstrated that ECMO specialists with more than 1 year of experience outperformed the specialists with less than 1 year of experience. Participants endorsed these sessions as important and representative of events that might be encountered in practice.

Conclusions

The scenarios could serve as a component of an ECMO education curriculum and be used to assess clinical specialists’ readiness to manage ECMO emergencies.
Laparoscopic Versus Open Adhesiolysis for Small Bowel Obstruction: A Single-Center Retrospective Case-Control Study
Authors: Lin Hao , Li Jiante , Xie Zhiyuan , Zhang Wentao , Lv Xiaopeng
Published: April 2016

Aim:

This study is to investigate the short-term outcomes of small bowel obstruction (SBO) patients undergoing laparoscopic versus open adhesiolysis.

Patients and Methods:

A total of 202 patients with SBO were enrolled in this study. The patients underwent either laparoscopic (n=101) or open adhesiolysis (n=101). The primary end point was 30-day overall complications and secondary outcomes included major complications such as superficial and deep wound infections, mortality, postoperative length of stay, and operative time.

Results:

There was no statistically significant difference in the demographic parameters between laparoscopic and open adhesiolysis populations. The mean operative time for laparoscopic adhesiolysis was significantly less than open adhesiolysis (70±34.2 vs. 101±50.2, P=0.01). Statistically significant differences in flatus day (3.5±1.2 vs. 4.5±1.8, P=0.035) and postoperative hospital stay (6.4±2.1 vs. 7.2±2.9, P=0.041) were identified in favor of laparoscopic group, whereas the medical expenses for both groups were not different (31012.0±3412.9 vs. 30029.0±3100.9, P>0.05). The overall complications for open and laparoscopic group were 19.8% and 9.9%, respectively (P=0.048). The important factors that led to a significantly lower overall complications rate in laparoscopic group might result from the lower wound (9.9% vs. 2.0%, P=0.017) and infectious (10.9% vs. 3.0%, P=0.027) complications.

Conclusions:

The laparoscopic approach for SBO is feasible because of its fewer complications and hospital stay.
Pelvic Floor Symptoms and Spinal Curvature in Women
Authors: Meyer Isuzu , McArthur Tatum A. , Tang Ying , McKinney Jessica L. , Morgan Sarah L. , Richter Holly E.
Published: April 2016

Objectives

To characterize the association between thoracic (T) and lumbar (L) spinal curvature and pelvic floor (PF) symptoms (pelvic organ prolapse, urinary incontinence [UI], fecal incontinence [FI]).

Methods

Of women undergoing a bone mineral density scan from January 2007 to October 2010, patients who completed PF symptom questionnaires and had T and/or L spine radiographs or computed tomography examinations within 3 years of questionnaire completion were included in this study. The spine angles were measured using the Cobb angle method. The T and L curvatures were categorized as hypokyphosis (<20°), normal T kyphosis (20–40°), hyperkyphosis (>40°), hypolordosis (<40°), normal L lordosis (40–70°), and hyperlordosis (>70°). The presence and type of UI were identified with the 3 Incontinence Questionnaire and FI with the Modified Manchester Questionnaire. Pelvic organ prolapse was defined as a positive response to the presence of a bulge question from the PF Distress Inventory-20.

Results

Of 1665 eligible women, 824 and 302 (mean age 64 ± 10 for both) had T and L spine images, respectively. No differences in PF symptoms were observed in the T or L spine groups categorized by hypo-, normal, and hyperkyphosis/lordosis except for urgency UI being more prevalent in the hypolordosis group (P = 0.01). However, upon further characterization using logistic regression, no association was noted between PF symptoms and T or L spine angles; no differences in the mean angles were found between women with versus without PF symptoms (P ≥ 0.05).

Conclusions

The current study shows that the T and L spinal curvatures are not associated with the presence of PF symptoms.
Is Occult Stress Urinary Incontinence a Reliable Predictive Marker?
Authors: Manodoro Stefano , Spelzini Federico , Frigerio Matteo , Nicoli Elena , Verri Debora , Milani Rodolfo
Published: April 2016

Objective

Pelvic reconstructive surgery can be associated to correction, persistence, or onset of stress urinary incontinence. The aim of our study was to evaluate the incidence of stress incontinence (SI) after prolapse repair in 3 groups with different preoperative urodynamic findings and to find out the predictiveness of occult SI.

Methods

Patients undergoing vaginal hysterectomy, uterus-sacral ligament colposuspension, and traditional anterior repair for pelvic prolapse were retrospectively analyzed. No patient underwent any additional anti-incontinence procedure. Preoperative evaluation included clinical history, physical examination, and urodynamic assessment with a pessary reduction test. According to urodynamic findings, women were divided into SI (A), occult SI (B), and continence (C) groups. Primary outcome was to compare the incidence of postoperative SI among groups. Secondary outcome was to assess postoperative quality of life with International Consultation on Incontinence questionnaire-short form questionnaire.

Results

One hundred fifty patients were analyzed (A: n = 30; B: n = 43; C: n = 77). Mean follow-up was 18.4 ± 0.9 months without differences among groups. Patients in group B did not have higher postoperative SI rate compared to group C. There were no differences in International Consultation on Incontinence questionnaire-short form scores in symptomatic women among groups.

Conclusions

In our series, occult stress urinary incontinence is a poor urodynamic marker to predict the development of postoperative SI.
Effect of Supervised Pelvic Floor Biofeedback and Electrical Stimulation in Women With Mixed and Stress Urinary Incontinence
Authors: Richmond Cherrilyn F. , Martin Deanna K. , Yip Sallis O. , Dick Madeline A. , Erekson Elisabeth A.
Published: April 2016

Objective

The aim of this study was to compare the symptomatic change in urinary symptom distress before and after treatment with pelvic floor biofeedback and electrical stimulation in women with mixed urinary incontinence (MUI) and stress urinary incontinence (SUI).

Methods

We conducted a retrospective cohort study of women who underwent supervised pelvic floor biofeedback therapy and electrostimulation for the treatment of MUI and SUI. Our primary outcome was change in the Urinary Distress Inventory-6 (UDI-6) score before and after therapy.

Results

Overall, a significant drop in UDI-6 score was seen in women with MUI (mean decrease, 29.1 [27.5]; P < 0.001), and a nonsignificant drop was seen in women with SUI (mean decrease, 6.8 [20.3]; P = 0.07) after treatment. Significantly greater change in UDI-6 score from baseline to follow-up was noted in women with MUI compared with those with SUI (P = 0.002).

Conclusions

Women with MUI have greater urinary distress symptoms than women with SUI. Both women with MUI and SUI experienced significant improvement in their urinary distress symptoms after pelvic floor biofeedback and electrostimulation.
New Measures for Predicting Birth-Related Pelvic Floor Trauma
Authors: Rostaminia Ghazaleh , Peck Jennifer D. , Van Delft Kim , Thakar Ranee , Sultan Abdul , Shobeiri S. Abbas
Published: April 2016

Objectives

The aim of this study was to establish the predictive role of obstetric variables for obstetric outcomes and birth related levator ani muscle (LAM) trauma.

Methods

In this prospective study, women underwent 3-dimensional pelvic floor ultrasound at their first appointment at 36 weeks and also 3 months postpartum. The measurements included minimal levator hiatus circumference (MLHC) and the ratio of fetal head circumference to MLHC = head-induced stretch ratio (HISR) as an indicator of the discrepancy between passage and passing canal. To derive the true impact of baby's mass on the levator ani musculature, we devised the levator ani stretch ratio (LASR), which was calculated by multiplying the HISR and the baby's weight.

Results

Data set of 173 women was available for analysis. Mean HISR and LASR values were statistically different across all binary outcome categories, with 1 exception for HISR and levator ani injury. The odds ratios for LASR indicated positive and statistically significant associations with all obstetric outcomes examined. The probability of the LASR correctly classifying those with the adverse obstetric outcome, as estimated by the area under the curve, ranged from 0.64 to 0.80 with the strongest discriminatory ability observed for severe LAM trauma.

Conclusions

Fetal head circumference/mother MLHC ratio (HISR) is associated with longer length of second stage of labor, assisted delivery, and increased severity of perineal trauma. Similar associations were observed for LASR, but in addition, LASR had good discriminatory ability to identify severe LAM trauma.
Rescue Therapy Using Rituximab for Multiple Sclerosis
Authors: Berenguer-Ruiz Leticia , Sempere Angel P. , Gimenez-Martinez Juana , Gabaldon-Torres Laura , Tahoces Luisa , Sanchez-Perez Rosa , Diaz-Marin Carmen
Published: April 2016

Objectives

The aim of the study was to describe the effectiveness and safety data of rituximab in a group of patients with relapsing-remitting multiple sclerosis (MS) treated with rituximab due to failure of previous treatments or concomitant autoimmune diseases.

Methods

This is an observational study. Rituximab was considered in case of failure of the second-line therapy, failure of the first-line therapy and a contraindication to second-line therapies, or concomitant autoimmune disease. Relapses, the Expanded Disability Status Scale, the EQ VAS, and magnetic resonance imaging activity were assessed.

Results

This study included 12 patients with relapsing-remitting MS. The mean (range) age of the patients was 35 (19–54) years. Ten patients were treated with rituximab because of treatment failure, and 2 patients were treated with rituximab because of the development of idiopathic thrombocytopenic purpura. The mean (range) follow-up duration after beginning rituximab was 40 (18–72) months. Rituximab was well tolerated, because no patient experienced serious adverse reactions or discontinued treatment. During treatment with rituximab, no patient suffered a clinical relapse, and magnetic resonance imaging activity was not detected. The Expanded Disability Status Scale scores improved in 11 of 12 patients and remained stable in 1 patient. The EuroQol visual analogue scale scores improved in 8 of 9 patients in whom the EuroQol visual analogue scale was assessed.

Conclusions

Treatment with rituximab seems to be safe and effective for some patients with relapsing-remitting MS who have failed to respond to first- and second-line therapies and may also be a useful option for patients with concomitant autoimmune disorders.
Statin Use and Cognitive Impairment in Patients With Type 1 Diabetes: An Observational Study
Authors: Moryś Joanna M. , Kozera Grzegorz M. , Neubauer-Geryk Jolanta , Kruszewski Piotr , Wolnik Bogumił , Nyka Walenty M. , Bieniaszewski Leszek
Published: April 2016

Objective

We aimed to assess a wide range of cognitive functions in patients with type 1 diabetes (DM1) compared with healthy control subjects and to evaluate the effects of statins on cognitive functions in DM1 patients.

Materials and Methods

The sample studied consisted of 55 DM1 patients (80.0% with hyperlipidemia, 20% with statin treatment) and 36 age-matched control subjects (77.8% with hyperlipidemia) without diabetes or statin use. Their cognitive functions (attention, memory, and executive functions) were evaluated with the trail making test, controlled oral word association test (COWAT), Rey-Osterrieth complex figure test, brain damage test (diagnosticum für cerebralschädigung, DCS), Wisconsin card sorting test (WCST), and digit span and block design tests from the revised Wechsler adult intelligence scale.

Results

Cognitive performance was impaired in DM1 patients when compared with the control group with regard to semantic verbal fluency (COWAT_animals), visual learning (DCS), conceptual-level responses, executive functions (WCST random errors), and WCST trials to complete the first category. Subgroups of DM1 patients distinguished on the basis of statin therapy did not differ with regard to verbal fluency (COWAT_animals), visual learning (DCS), conceptual-level responses, executive functions (WCST random errors), and WCST trials to complete the first category. Multivariate analysis also does not show the impact of statin therapy on cognitive functioning regardless of the duration of education, microangiopathic evidence, the presence of hyperlipidemia, or antihypertensive therapy.

Conclusions

We find impairment of cognitive functions in DM1 patients when compared with control subjects without diabetes. However, we show neither the effect of statins nor the significant influence of metabolic control, microangiopathic complications, or the presence of hyperlipidemia on cognitive functions in DM1 patients.
On contextuality in behavioural data
Authors: Dzhafarov Ehtibar N. , Kujala Janne V. , Cervantes Víctor H. , Zhang Ru , Jones Matt
Published: April 2016

Dzhafarovet al.(Dzhafarovet al.2016Phil. Trans. R. Soc. A374, 20150099. (doi:10.1098/rsta.2015.0099)) reviewed several behavioural datasets imitating the formal design of the quantum-mechanical contextuality experiments. The conclusion was that none of these datasets exhibited contextuality if understood in the generalized sense proposed by Dzhafarovet al.(2015Found. Phys.7, 762–782. (doi:10.1007/s10701-015-9882-9)), while the traditional definition of contextuality does not apply to these data because they violate the condition of consistent connectedness (also known as marginal selectivity, no-signalling condition, no-disturbance principle, etc.). In this paper, we clarify the relationship between (in)consistent connectedness and (non)contextuality, as well as between the traditional and extended definitions of (non)contextuality, using as an example the Clauser–Horn–Shimony–Holt inequalities originally designed for detecting contextuality in entangled particles.
Grounding the randomness of quantum measurement
Authors: Jaeger Gregg
Published: April 2016

Julian Schwinger provided to physics a mathematical reconstruction of quantum mechanics on the basis of the characteristics of sequences of measurements occurring at the atomic level of physical structure. The central component of this reconstruction is an algebra of symbols corresponding to quantum measurements, conceived of as discrete processes, which serve to relate experience to theory; collections of outcomes of identically circumscribed such measurements are attributed expectation values, which constitute the predictive content of the theory. The outcomes correspond to certain phase parameters appearing in the corresponding symbols, which are complex numbers, the algebra of which he finds by a process he refers to as ‘induction’. Schwinger assumed these (individually unpredictable) phase parameters to take random, uniformly distributed definite values within a natural range. I have previously suggested that the ‘principle of plenitude’ may serve as a basis in principle for the occurrence of the definite measured values that are those members of the collections of measurement outcomes from which the corresponding observed statistics derive (Jaeger 2015
Found. Phys.
45, 806–819. (
doi:10.1007/s10701-015-9893-6
)). Here, I evaluate Schwinger's assumption in the context of recent critiques of the notion of randomness and explicitly relate the randomness of these phases with the principle of plenitude and, in this way, provide a fundamental grounding for the objective, physically irreducible probabilities, conceived of as graded possibilities, that are attributed to measurement outcomes by quantum mechanics.
Note on entropies for quantum dynamical systems
Authors: Watanabe Noboru
Published: April 2016

Quantum entropy and channel are fundamental concepts for quantum information theory progressed recently in various directions. We will review the fundamental aspects of mean entropy and mean mutual entropy and calculate them for open system dynamics.
Three-body system metaphor for the two-slit experiment andEscherichia colilactose–glucose metabolism
Authors: Asano Masanari , Khrennikov Andrei , Ohya Masanori , Tanaka Yoshiharu , Yamato Ichiro
Published: April 2016

We compare the contextual probabilistic structures of the seminal two-slit experiment (quantum interference experiment), the system of three interacting bodies andEscherichia colilactose–glucose metabolism. We show that they have the same non-Kolmogorov probabilistic structure resulting from multi-contextuality. There are plenty of statistical data with non-Kolmogorov features; in particular, the probabilistic behaviour of neither quantum nor biological systems can be described classically. Biological systems (even cells and proteins) are macroscopic systems and one may try to present a more detailed model of interactions in such systems that lead to quantum-like probabilistic behaviour. The system of interactions between three bodies is one of the simplest metaphoric examples for such interactions. By proceeding further in this way (by playing withn-body systems) we shall be able to find metaphoric mechanical models for complex bio-interactions, e.g. signalling between cells, leading to non-Kolmogorov probabilistic data.
Quantum Bayesianism as the basis of general theory of decision-making
Authors: Khrennikov Andrei
Published: April 2016

We discuss the subjective probability interpretation of the quantum-like approach to decision making and more generally to cognition. Our aim is to adopt the subjective probability interpretation of quantum mechanics, quantum Bayesianism (QBism), to serve quantum-like modelling and applications of quantum probability outside of physics. We analyse the classical and quantum probabilistic schemes of probability update, learning and decision-making and emphasize the role of Jeffrey conditioning and its quantum generalizations. Classically, this type of conditioning and corresponding probability update is based on the formula of total probability—one the basic laws of classical probability theory.
Comparative genomics and evolution of transcriptional regulons in Proteobacteria
Authors: Leyn Semen A. , Suvorova Inna A. , Kazakov Alexey E. , Ravcheev Dmitry A. , Stepanova Vita V. , Novichkov Pavel S. , Rodionov Dmitry A.
Published: April 2016

Comparative genomics approaches are broadly used for analysis of transcriptional regulation in bacterial genomes. In this work, we identified binding sites and reconstructed regulons for 33 orthologous groups of transcription factors (TFs) in 196 reference genomes from 21 taxonomic groups of Proteobacteria. Overall, we predict over 10 600 TF binding sites and identified more than 15 600 target genes for 1896 TFs constituting the studied orthologous groups of regulators. These include a set of orthologues for 21 metabolism-associated TFs from Escherichia coli and/or Shewanella that are conserved in five or more taxonomic groups and several additional TFs that represent non-orthologous substitutions of the metabolic regulators in some lineages of Proteobacteria. By comparing gene contents of the reconstructed regulons, we identified the core, taxonomy-specific and genome-specific TF regulon members and classified them by their metabolic functions. Detailed analysis of ArgR, TyrR, TrpR, HutC, HypR and other amino-acid-specific regulons demonstrated remarkable differences in regulatory strategies used by various lineages of Proteobacteria. The obtained genomic collection of in silico reconstructed TF regulons contains a large number of new regulatory interactions that await future experimental validation. The collection provides a framework for future evolutionary studies of transcriptional regulatory networks in Bacteria. It can be also used for functional annotation of putative metabolic transporters and enzymes that are abundant in the reconstructed regulons.
Exploiting Homeostatic Repopulation to Increase DC Vaccine Efficacy in Multiple Myeloma
Authors: Gatenbee Chandler D. , Folguera-Blasco Núria , Daneils Charlie , Gallaher Jill , Rockne Russell C. , Adams Casey , Nicholson Michael , Maniati Eleni , Kennedy John , Luddy Kimberly , Locke Frederick L. , Robertson-Tessi Mark
Published: April 2016

Standard of care for multiple myeloma involves autologous hematopoietic cell transplant (AHCT), which can extend life by a year; however the disease remains incurable. A dendritic cell vaccine developed at Moffitt will be used both immediately before and after AHCT, with the aim of achieving complete response. Data will be collected during the trial to test the biological activity of the vaccine. This data will parameterize a model that facilitates the exploration of outcomes when varying the timing of vaccination. This calibrated model will also inform the design of a follow-up trial, which will include vaccination in conjunction with other immunotherapies.
High-resolution interrogation of functional elements in the noncoding genome
Authors: Sanjana Neville E. , Wright Jason , Zheng Kaijie , Shalem Ophir , Fontanillas Pierre , Joung Julia , Cheng Christine , Regev Aviv , Zhang Feng
Published: April 2016

The noncoding genome plays a major role in gene regulation and disease yet we lack tools for rapid identification and manipulation of noncoding elements. Here, we develop a large-scale CRISPR screen employing ~18,000 sgRNAs targeting >700 kb of noncoding sequence in an unbiased manner surrounding three genes (NF1, NF2, andCUL3) involved in resistance to the BRAF inhibitor vemurafenib in theBRAF-mutant melanoma cell line A375. We identify specific noncoding locations near genes that modulate drug resistance when mutated. These sites have predictive hallmarks of noncoding function, such as physical interaction with gene promoters, evolutionary conservation and tissue-specific chromatin accessibility. At a subset of identified elements at theCUL3locus, we show that engineered mutations lead to a loss of gene expression associated with changes in transcription factor occupancy and in long-range and local epigenetic environments, implicating these sites in gene regulation and chemotherapeutic resistance. This demonstration of an unbiased mutagenesis screen across large noncoding regions expands the potential of pooled CRISPR screens for fundamental genomic discovery and for elucidating biologically relevant mechanisms of gene regulation.
Mega-analysis of 31,396 individuals from 6 countries uncovers strong gene-environment interaction for human fertility
Authors: Tropf Felix C. , Verweij Renske M. , van der Most Peter J. , Stulp Gert , Bakshi Andrew , Briley Daniel A. , Robinson Matthew , Numan Anastasia , Esko Tõnu , Metspalu Andres , Medland Sarah E. , Martin Nicholas G. , Snieder Harold , Lee S. Hong , Mills Melinda C.
Published: April 2016

Family and twin studies suggest that up to 50% of individual differences in human fertility within a population might be heritable. However, it remains unclear whether the genes associated with fertility outcomes such as number of children ever born (NEB) or age at first birth (AFB) are the same across geographical and historical environments. By not taking this into account, previous genetic studies implicitly assumed that the genetic effects are constant across time and space. We conduct a mega-analysis applying whole genome methods on 31,396 unrelated men and women from six Western countries. Across all individuals and environments, common single-nucleotide polymorphisms (SNPs) explained only ~4% of the variance in NEB and AFB. We then extend these models to test whether genetic effects are shared across different environments or unique to them. For individuals belonging to the same population and demographic cohort (born before or after the 20thcentury fertility decline), SNP-based heritability was almost five times higher at 22% for NEB and 19% for AFB. We also found no evidence suggesting that genetic effects on fertility are shared across time and space. Our findings imply that the environment strongly modifies genetic effects on the tempo and quantum of fertility, that currently ongoing natural selection is heterogeneous across environments, and that gene-environment interactions may partly account for missing heritability in fertility. Future research needs to combine efforts from genetic research and from the social sciences to better understand human fertility.

Authors Summary

Fertility behavior – such as age at first birth and number of children – varies strongly across historical time and geographical space. Yet, family and twin studies, which suggest that up to 50% of individual differences in fertility are heritable, implicitly assume that the genes important for fertility are the same across both time and space. Using molecular genetic data (SNPs) from over 30,000 unrelated individuals from six different countries, we show that different genes influence fertility in different time periods and different countries, and that the genetic effects consistently related to fertility are presumably small. The fact that genetic effects on fertility appear not to be universal could have tremendous implications for research in the area of reproductive medicine, social science and evolutionary biology alike.
High-Throughput Sequencing of Transposable Element Insertions Suggests Adaptive Evolution of the Invasive Asian Tiger Mosquito Towards Temperate Environments
Authors: Goubert Clément , Henri Hélène , Minard Guillaume , Valiente Moro Claire , Mavingui Patrick , Vieira Cristina , Boulesteix Matthieu
Published: April 2016

Invasive species represent unique opportunities to evaluate the role of local adaptation during colonization of new environments. Among these species, the Asian tiger mosquito,Aedes albopictus, is a threatening vector of several human viral diseases, including dengue and chikungunya, and raises concerns about the Zika fever. Its broad presence in both temperate and tropical environments has been considered the reflection of great “ecological plasticity”. However, no study has been conducted to assess the role of adaptive evolution in the ecological success ofAe. albopictusat the molecular level. In the present study, we performed a genomic scan to search for potential signatures of selection leading to local adaptation in one-hundred-forty field-collected mosquitoes from native populations of Vietnam and temperate invasive populations of Europe. High-throughput genotyping of transposable element insertions led to the discovery of more than 120 000 polymorphic loci, which, in their great majority, revealed a virtual absence of structure between the bio-geographic areas. Nevertheless, 92 outlier loci showed a high level of differentiation between temperate and tropical populations. The majority of these loci segregates at high insertion frequencies among European populations, indicating that this pattern could have been caused by recent adaptive evolution events in temperate areas. An analysis of the overlapping and neighboring genes highlighted several candidates, including diapause, lipid and juvenile hormone pathways.