bluuebunny/crossref_metadata_2025 huggingface dataset:
Poor work ability increases sickness absence over 10 years
Authors: Palmlöf L , Skillgate E , Talbäck M , Josephson M , Vingård E , Holm L W
Published: May 2019

Background

Little is known about the predictive value of single items from the work ability index (WAI) on the risk of sickness absence over several years, and whether such risk varies across age groups.

Aims

The aim of the study was to investigate whether poor self-perceived physical and mental work ability among employees in the public sector are associated with long-term sickness absence over a 10-year period.

Methods

The study was based on a prospective cohort of employees within the public sector in Sweden reporting ‘good health for working’. Baseline information was collected with questionnaires from 2000 to 2003. Poor physical and mental work ability in relation to work demands were assessed with two items from the WAI. The outcome was the number of years of long-term sickness absence between 2003 and 2012. Long-term sickness absence was defined as ≥28 days of sickness and this information was retrieved from Swedish National Registers. Crude and adjusted incidence rate ratios were calculated with analyses stratified by age.

Results

Compared with those reporting very good physical work ability, employees reporting any lower grade of physical work ability had a higher risk of long-term sickness absence across all age strata, with higher risk estimates in the highest age groups and 6-fold increased risk in the oldest age group. Similar results were found for mental work ability with an almost 4-fold increased risk in the highest age group.

Conclusions

Self-reported physical and mental poor work ability are associated with long-term sickness absence during the subsequent 10 years. The risk increases with age.
A regularization approach to the minimum distance estimation: application to structural macroeconomic estimation using IRFs
Authors: Sokullu Senay
Published: May 2019

This article considers the invertibility problem of the optimal weighting matrix encountered during Impulse Response Function Matching Estimation (IRFME) of Dynamic Stochastic General Equilibrium (DSGE) Models. We propose to use a regularized inverse and derive the asymptotic properties of the estimator. We show that the asymptotic distribution of our estimator converges to that of the optimal estimator which has important implications for testing the fit of the model. We demonstrate the small sample properties of the estimator by Monte Carlo simulation exercises. Finally, we use our estimator to estimate the model in Altig et al.
Opinions et positions de médecins à l’endroit de la punition corporelle comme pratique parentale disciplinaire
Authors: Clément Marie-Ève , Gagné Marie-Hélène , Dufour Sarah , Frappier Jean-Yves
Published: May 2019

Contexte de l’étude

Les médecins sont parmi les professionnels les plus sollicités par les parents pour obtenir des conseils sur l’exercice du rôle parental. Pourtant, ils sont rarement formés pour informer les parents, et particulièrement en ce qui concerne la légitimité des pratiques disciplinaires comme la punition corporelle (PC).

Objectifs

Cette étude vise à documenter les attitudes de médecins québécois en faveur de la PC ainsi que leur pratique de soutien auprès des parents.

Méthodes

Au total 113 médecins œuvrant au moins 20% du temps avec des enfants mineurs ou leurs parents ont complété un sondage en ligne sur leurs caractéristiques personnelles et professionnelles, leurs connaissances et attitudes face à la PC et leurs pratiques de soutien.

Résultats

Les résultats montrent que les répondants connaissent bien les balises légales de l’article 43 du Code criminel canadien qui encadrent le recours aux PC et qu’ils sont en désaccord avec cette méthode disciplinaire. Lorsqu’ils soupçonnent une situation de PC envers un enfant, les médecins répondants offrent diverses modalités de soutien aux parent (ex.: aborder le sujet, proposer d’autres pratiques disciplinaires), ce qui est moins souvent le cas lorsque la situation implique un adolescent. Enfin, les résultats montrent que certains facteurs sont associés aux pratiques de soutien des répondants, dont les attitudes face aux PC et le sentiment d’être suffisamment formé pour aborder les pratiques disciplinaires avec les parents.

Conclusions

Ces résultats soulignent l’importance d’outiller et de soutenir les médecins dans leurs interventions auprès des parents en difficulté.
The Alkaline Lamprophyres of the Dolomitic Area (Southern Alps, Italy): Markers of the Late Triassic Change from Orogenic-like to Anorogenic Magmatism
Authors: Casetta Federico , Ickert Ryan B , Mark Darren F , Bonadiman Costanza , Giacomoni Pier Paolo , Ntaflos Theodoros , Coltorti Massimo
Published: May 2019

We present the first complete petrological, geochemical and geochronological characterization of the oldest lamprophyric rocks in Italy, which crop out around Predazzo (Dolomitic Area), with the aim of deciphering their relationship with Triassic magmatic events across the whole of the Southern Alps. Their Mg# of between 37 and 70, together with their trace element contents, suggests that fractional crystallization was the main process responsible for their differentiation, together with small-scale mixing, as evidenced by some complex amphibole textures. Moreover, the occurrence of primary carbonate ocelli suggests an intimate association between the alkaline lamprophyric magmas and a carbonatitic melt. 40Ar/39Ar data show that the lamprophyres were emplaced at 219·22 ± 0·73 Ma (2σ; full systematic uncertainties), around 20 Myr after the high-K calc-alkaline to shoshonitic, short-lived, Ladinian (237–238 Ma) magmatic event of the Dolomitic Area. Their trace element and Sr–Nd isotopic signatures (87Sr/86Sri = 0·7033–0·7040; 143Nd/144Ndi = 0·51260–0·51265) are probably related to a garnet–amphibole-bearing lithosphere interacting with an asthenospheric component, significantly more depleted than the mantle source of the high-K calc-alkaline to shoshonitic magmas. These features suggest that the Predazzo lamprophyres belong to the same alkaline–carbonatitic magmatic event that intruded the mantle beneath the Southern Alps (e.g. Finero peridotite) between 190 and 225 Ma. In this scenario, the Predazzo lamprophyres cannot be considered as a late-stage pulse of the orogenic-like Ladinian magmatism of the Dolomitic Area, but most probably represent a petrological bridge to the opening of the Alpine Tethys.
Exploring the Meaning of Cognitive Behavioral Therapy for Insomnia for Patients with Chronic Pain
Authors: Koffel Erin , Amundson Erin , Wisdom Jennifer P
Published: May 2019

Objective

Insomnia is one of the most common, persistent, and distressing symptoms associated with chronic pain. Cognitive behavioral therapy for insomnia (CBT-I) is the firstline treatment for insomnia, but patient preferences and perspectives about CBT-I within the context of chronic pain are unknown. The current qualitative study sought to understand the experience of CBT-I among patients with chronic pain, including aspects of CBT-I that were found to be difficult (e.g., pain as a specific barrier to adherence/dropout), changes in sleep and pain functioning after CBT-I, and aspects of CBT-I that were appreciated.

Design

Qualitative semistructured interviews.

Methods

We conducted individual semistructured interviews with 17 veterans with chronic pain and insomnia who had recently participated in CBT-I, as well as their CBT-I therapists, and used thematic analysis to identify conceptual themes.

Results

Results revealed that patients and CBT-I therapists found changing sleep habits during CBT-I challenging due to anxiety and temporary increases in fatigue, but did not identify major pain-related barriers to adhering to CBT-I recommendations; patients experienced better sleep, mood, energy, and socialization after CBT-I despite minimal changes in pain intensity; and patients highly valued CBT-I as a personalized treatment for sleep and strongly recommended it for other patients with chronic pain.

Conclusions

Findings of improved sleep and functional outcomes support efforts to incorporate CBT-I into chronic pain treatment, including educating patients and providers about the strong feasibility of improving sleep and quality of life despite ongoing pain.
Assessing Emotional Intelligence of Graduate Probationer Police Officers: A UK Pilot Study
Authors: McDowall Almuth , Brown Jennifer , Gamblin David
Published: May 2019

The present article summarizes a small-scale pilot study as part of a wider research programme to understand and track learner motivations and characteristics as they change and develop over the course of a policing education and training programme. Emotional intelligence (EI), enabling capacity to recognize and work with emotions, is crucial in policing given demanding interactions with the public and inherently stressful role demands. We assessed levels of EI in a group of participants (N = 84) from the Police Now leadership training programme. Using an established psychometric EI assessment, Emotions and Behaviours at Work, scores were collected and benchmarked. Results showed that participants rated themselves as comparatively low on Influence and Decisiveness and high on Conscientiousness and Rules. We discuss findings in terms of attitudes to the public and towards evidence-based policing, as well as potential selection, training, and research implications.
Professionalizing Contingency: How Journalism Schools Adapt to Deprofessionalization
Authors: Besbris Max , Petre Caitlin
Published: May 2019

Many professional labor markets are currently experiencing signs of deprofessionalization, including automation of tasks and increasingly unstable employment conditions. Drawing on the case of journalism schools, this article examines how these shifts affect professional education, which has historically been positioned as a means to avoiding precarious employment. How do professional schools cope with inimical disruptions to the labor markets for which they are training students? Based on 113 in-depth interviews with faculty, staff, and administrators from 44 U.S. journalism programs, we argue that journalism schools have sought to reframe labor market instability as an inevitable and even desirable aspect of journalistic practice and professional identity. They do this by dismantling boundaries, valorizing entrepreneurialism, and seeking to alter institutional practices to emphasize skills over abstract knowledge. Taken together, we call this professionalizing contingency. As labor market precarity continues to spread within expert and professional fields, our findings have implications for broader sociological understandings of professional education.
Introduction of a trust law in Switzerland
Authors: Peter Natalie
Published: May 2019

On a governmental level, the introduction of a Swiss law on trusts is currently being reviewed. It is argued that an introduction would have various advantages, for example citizens would be offered an instrument that is subject to the domestic legal system being more accessible and easier to understand, and providing clarity, leading to greater transparency and legal certainty. In addition, new areas of activity would be created for Swiss professionals to advise on trusts, to set up trusts and to manage trusts and their assets. This article analyses whether the trust is a suitable instrument or whether it would be more advisable to review the existing instruments, such as the Swiss family foundation or the fiducie (Treuhand), and to amend them accordingly.
Investigations on the Relationship Between Ovarian, Endocrine, and Renal Findings in Nonclinical Safety Studies of the γ-Secretase Inhibitor Avagacestat
Authors: Simutis Frank J , Sanderson Thomas P , Pilcher Gary D , Graziano Michael J
Published: May 2019

Avagacestat, a gamma (γ)-secretase inhibitor that was in development for treatment of Alzheimer’s disease, produced ovarian granulosa-thecal cell tumors in rats and dogs and a glomerulopathy with profound proteinuria in female rats. This report describes the results of follow-up investigative studies, including the use of ovariectomized (OVX) rats, to further characterize these findings and determine their mechanism(s). Ovarian proliferative changes in rats likely resulted from: (1) inhibition of Notch signaling pathways regulating ovarian follicular differentiation/development, characterized microscopically as altered ovarian cyclicity and/or ovarian follicular degeneration; (2) subsequent disruption of the hypothalamic-pituitary-ovarian axis due to ovarian atrophy with decreases in serum estrogen and progesterone (as low as 0.45× and 0.21× controls, respectively); and (3) chronic gonadotropin stimulation and pituitary hypertrophy/hyperplasia in response to the absence of negative feedback. Gonadotropin stimulation in rats was confirmed by increases in serum follicle-stimulating hormone (up to 7.75× controls) and luteinizing hormone (up to 5.84×). A similar nongenotoxic mechanism was likely responsible for the ovarian findings in dogs although changes in serum hormone levels were not detected. The dose- and time-dependent glomerulopathy with progression to chronic progressive nephropathy in female rats appears to be a direct effect of avagacestat and was not ameliorated with coadministration of 17β-estradiol or an antihypertensive (enalapril) and was not present in control OVX rats. In contrast, adrenocortical hypertrophy in female rats was considered secondary to ovarian changes based on the absence of this finding in avagacestat-treated OVX rats and no increase in adrenocorticotropic hormone staining in the pituitary.
Unimproved water sources and open defecation are associated with active trachoma in children in internally displaced persons camps in the Darfur States of Sudan
Authors: Macleod Colin K , Binnawi Kamal Hashim , Elshafie Balgesa Elkheir , Sadig Husam Eldin , Hassan Awad , Cocks Naomi , Willis Rebecca , Chu Brian , Solomon Anthony W ,   for the Global Trachoma Mapping Project
Published: May 2019

Purpose

To estimate the proportion of children with trachomatous inflammation—follicular (TF) and adults with trachomatous trichiasis (TT) in internally displaced persons (IDP) camps in the Darfur States of Sudan and to evaluate associated risk factors.

Methods

IDP camps were identified from government census data. We conducted a subanalysis of data collected in these camps during 2014–2015 as part of surveys covering 37 districts of the Darfur States within the Global Trachoma Mapping Project. A random-effects hierarchical model was used to evaluate factors associated with TF in children or TT in adults.

Results

Thirty-six IDP camps were represented in the survey data, in which 1926 children aged 1–9 y were examined, of whom 38 (8%) had TF. Poor sanitation, younger age and living in a household that purchased water from a vendor were associated with TF in children aged 1–9 y. Of 2139 individuals examined aged ≥15 y, 16 (0.7%) had TT. TT was strongly independently associated with being older and living alone.

Conclusion

Trachoma is found at low levels in these camps, but still at levels where intervention is needed. Disease elimination in conflict-related settings presents a unique challenge for the trachoma community, and may require an innovative approach. Understanding how best to undertake trachoma elimination interventions in these areas should be prioritized.
Cryptic Infection and Systemic Colonization of Leguminous Crops by Verticillium dahliae, the Cause of Verticillium Wilt
Authors: Lloyd M. G. , McRoberts N. , Gordon T. R.
Published: May 2019

Verticillium dahliae, the cause of Verticillium wilt, is a widespread pathogen that affects many crops in California and throughout the world. Cover cropping with leguminous species is often integrated into a rotation scheme for its contribution to soil nitrogen, and can contribute to management of Verticillium wilt provided the chosen crop does not support development of V. dahliae. Seven cool season legumes (faba bean, bell bean, field pea, hairy vetch, common vetch, purple vetch, and woollypod vetch), and three warm season legumes (sesbania, sunn hemp, and black-eyed pea) were evaluated as hosts for reproductive growth of V. dahliae. All 10 legumes were colonized by V. dahliae, while remaining symptomless, when subjected to a root-dip inoculation. Similar results were obtained when plants were grown in infested potting soil, albeit with a lower frequency of infection than in root-dip assays. All tested legumes were also infected in field trials, with the exception of bell bean. Overall, warm season legumes sustained higher rates of infection than cool season legumes. Common vetch was the most extensively colonized of the cool season legumes. Based on the results of this study, legumes may not be an appropriate rotation crop in fields where Verticillium wilt is a problem.
Cooperation and Coordination in Plant Disease Management
Authors: Sherman Jennifer , Burke Jordan M. , Gent David H.
Published: May 2019

Scaling of management efforts beyond the boundaries of individual farms may require that individuals act collectively. Such approaches have been suggested several times in plant pathology contexts but rarely have been implemented, in part because the institutional structures that enable successful collective action are poorly understood. In this research, we conducted in-depth interviews with hop producers in Oregon and Washington State to identify their motivations for and barriers to collective action regarding communication of disease levels, coordination of management practices, and sharing of best management practices and other data for powdery mildew (caused by Podosphaera macularis). Growers were generally open to and engaged in communication with neighbors and others on disease status in their hop yards and some evidence of higher levels of information sharing on management practices was found. However, growers who had developed extensive knowledge and databases were reluctant to share information viewed as proprietary. Relationships, trust, and reciprocity were facilitating factors for communication and information sharing, whereas lack of these factors and social norms of independence and pride in portions of the grower community were identified as impediments. Given the heterogeneity of trust, lack of confidence in reciprocity, and weak shared norms, communication of disease risk and coordinated management may be most successful if directed at a smaller scale as a series of neighborhood-based partnerships of growers and their immediate neighbors. Developing a disease reporting system and coordinated disease management efforts with more producers and at larger spatial extents would require formalized structures and rules that would provide assurance that there is consistency in disease data collection and reporting, reciprocation, and sanctions for those who use the information for marketing purposes against other growers. Given the analyses presented here, we believe there is potential for collective action in disease management but with limitations on the scope and nature of the actions.
Bias in Radiology Resident Selection: Do We Discriminate Against the Obese and Unattractive?
Authors: Maxfield Charles M. , Thorpe Matthew P. , Desser Terry S. , Heitkamp Darel E. , Hull Nathan C. , Johnson Karen S. , Koontz Nicholas A. , Mlady Gary W. , Welch Timothy J. , Grimm Lars J.
Published: May 2019

Purpose

To evaluate for appearance-based discrimination in the selection of radiology residents.

Method

A deception study simulating the resident selection process examined the impact of attractiveness and obesity on resident selection. Seventy-four core faculty from 5 academic radiology departments reviewed mock residency applications in September and October 2017. Each application included demographic information and a photograph, representing a prespecified distribution of facial attractiveness and obesity, combined with randomized academic and supporting variables. Reviewers independently scored applications for interview desirability. Reviewer scores and application variables were compared using linear mixed fixed- and random-effects models.

Results

Reviewers evaluated 5,447 applications (mean: 74 applications per reviewer). United States Medical Licensing Examination Step 1 scores were the strongest predictor of reviewer rating (B = 0.35 [standard error (SE) = 0.029]). Applicant facial attractiveness strongly predicted rating (attractive vs unattractive, B = 0.30 [SE = 0.056]; neutral vs unattractive, B = 0.13 [SE = 0.028]). Less influential but still significant predictors included race/ethnicity (B = 0.25 [SE = 0.059]), preclinical class rank (B = 0.25 [SE = 0.040]), clinical clerkship grades (B = 0.23 [SE = 0.034]), Alpha Omega Alpha membership (B = 0.21 [SE = 0.032]), and obesity (vs not obese) (B = −0.14 [SE = 0.024]).

Conclusions

Findings provide preliminary evidence of discrimination against facially unattractive and obese applicants in radiology resident selection. Obesity and attractiveness were as influential in applicant selection for interview as traditional medical school performance metrics. Selection committees should invoke strategies to detect and manage appearance-based bias.
Health Systems Science: The “Broccoli” of Undergraduate Medical Education
Authors: Gonzalo Jed D. , Ogrinc Greg
Published: May 2019

Health system leaders are calling for reform of medical education programs to meet evolving needs of health systems. U.S. medical schools have initiated innovative curricula related to health systems science (HSS), which includes competencies in value-based care, population health, system improvement, interprofessional collaboration, and systems thinking. Successful implementation of HSS curricula is challenging because of the necessity for new curricular methods, assessments, and educators and for resource allocation. Perhaps most notable of these challenges, however, is students’ mixed receptivity. Although many students are fully engaged, others are dissatisfied with curricular time dedicated to competencies not perceived as high yield. HSS learning can be viewed as “broccoli”—students may realize it is good for them in the long term, but it may not be palatable in the moment. Further analysis is necessary for accelerating change both locally and nationally.

With over 11 years of experience in global HSS curricular reform in 2 medical schools and informed by the curricular implementation “performance gap,” the authors explore student receptivity challenges, including marginalization of HSS coursework, infancy of the HSS field, relative nascence of curricula and educators, heterogeneity of pedagogies, tensions in students’ perceptions of their professional role, and culture of HSS integration. The authors call for the reexamination of 5 issues influencing HSS receptivity: student recruitment processes, faculty development, building an HSS academic “home,” evaluation metrics, and transparent collaboration between medical schools. To fulfill the social obligation of meeting patients’ needs, educators must seek a shared understanding of underlying challenges of HSS innovations.
Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery
Authors: Anwar Sibtain , Cooper Jackie , Rahman Junia , Sharma Chhaya , Langford Richard
Published: May 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Persistent postsurgical pain is common and affects quality of life. The hypothesis was that use of pregabalin and ketamine would prevent persistent pain after cardiac surgery.

Methods

This randomized, double-blind, placebo-controlled trial was undertaken at two cardiac surgery centers in the United Kingdom. Adults without chronic pain and undergoing any elective cardiac surgery patients via sternotomy were randomly assigned to receive either usual care, pregabalin (150 mg preoperatively and twice daily for 14 postoperative days) alone, or pregabalin in combination with a 48-h postoperative infusion of intravenous ketamine at 0.1 mg · kg−1 · h−1. The primary endpoints were prevalence of clinically significant pain at 3 and 6 months after surgery, defined as a pain score on the numeric rating scale of 4 or higher (out of 10) after a functional assessment of three maximal coughs. The secondary outcomes included acute pain, opioid use, and safety measures, as well as long-term neuropathic pain, analgesic requirement, and quality of life.

Results

In total, 150 patients were randomized, with 17 withdrawals from treatment and 2 losses to follow-up but with data analyzed for all participants on an intention-to-treat basis. The prevalence of pain was lower at 3 postoperative months for pregabalin alone (6% [3 of 50]) and in combination with ketamine (2% [1 of 50]) compared to the control group (34% [17 of 50]; odds ratio = 0.126 [0.022 to 0.5], P = 0.0008; and 0.041 [0.0009 to 0.28], P < 0.0001, respectively) and at 6 months for pregabalin alone (6% [3 of 50]) and in combination with ketamine 0% (0 of 5) compared to the control group (28% [14 of 50]; odds ratio = 0.167 [0.029 to 0.7], P = 0.006; and 0.000 [0 to 0.24], P < 0.0001). Diplopia was more common in both active arms.

Conclusions

Preoperative administration of 150 mg of pregabalin and postoperative continuation twice daily for 14 days significantly lowered the prevalence of persistent pain after cardiac surgery.
Anesthesiology Resident Night Float Duty Alters Sleep Patterns
Authors: Dunn Lauren K. , Kleiman Amanda M. , Forkin Katherine T. , Bechtel Allison J. , Collins Stephen R. , Potter Jennifer F. , Kaperak Christopher J. , Tsang Siny , Huffmyer Julie L. , Nemergut Edward C.
Published: May 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Residency programs utilize night float systems to adhere to duty hour restrictions; however, the influence of night float on resident sleep has not been described. The study aim was to determine the influence of night float on resident sleep patterns and quality of sleep. We hypothesized that total sleep time decreases during night float, increases as residents acclimate to night shift work, and returns to baseline during recovery.

Methods

This was a single-center observational study of 30 anesthesia residents scheduled to complete six consecutive night float shifts. Electroencephalography sleep patterns were recorded during baseline (three nights), night float (six nights), and recovery (three nights) using the ZMachine Insight monitor (General Sleep Corporation, USA). Total sleep time; light, deep, and rapid eye movement sleep; sleep efficiency; latency to persistent sleep; and wake after sleep onset were observed.

Results

Mean total sleep time ± SD was 5.9 ± 1.9 h (3.0 ± 1.2.1 h light; 1.4 ± 0.6 h deep; 1.6 ± 0.7 h rapid eye movement) at baseline. During night float, mean total sleep time was 4.5 ± 1.8 h (1.4-h decrease, 95% CI: 0.9 to 1.9, Cohen’s d = –1.1, P < 0.001) with decreases in light (2.2 ± 1.1 h, 0.7-h decrease, 95% CI: 0.4 to 1.1, d = –1.0, P < 0.001), deep (1.1 ± 0.7 h, 0.3-h decrease, 95% CI: 0.1 to 0.4, d = –0.5, P = 0.005), and rapid eye movement sleep (1.2 ± 0.6 h, 0.4-h decrease, 95% CI: 0.3 to 0.6, d = –0.9, P < 0.001). Mean total sleep time during recovery was 5.4 ± 2.2 h, which did not differ significantly from baseline; however, deep (1.0 ± 0.6 h, 0.4-h decrease, 95% CI: 0.2 to 0.6, d = –0.6, P = 0.001 *, P = 0.001) and rapid eye movement sleep (1.2 ± 0.8 h, 0.4-h decrease, 95% CI: 0.2 to 0.6, d = –0.9, P < 0.001 P < 0.001) were significantly decreased.

Conclusions

Electroencephalography monitoring demonstrates that sleep quantity is decreased during six consecutive night float shifts. A 3-day period of recovery is insufficient for restorative sleep (rapid eye movement and deep sleep) levels to return to baseline.
Lumen-apposing Metal Stents, Fully Covered Self-expanding Metal Stents, and Biodegradable Stents in the Management of Benign of GI Strictures
Authors: Mohan Babu P. , Chandan Saurabh , Garg Rajat , Mohamed Shuaib , Shakhatreh Mohammed , Dugyala Sushma , Mashiana Harmeet S. , Ponnada Suresh , Asokkumar Ravishankar , Adler Douglas G.
Published: May 2019

Background:

Refractory benign gastrointestinal (GI) strictures are difficult to treat and placement of a stent is a commonly sought resort. Stents used for this purpose are fully covered self-expanding metal stent (FCSEMS), a biodegradable stent (BDS) and recently, a lumen-apposing metal stent (LAMS). There is no data comparing these stents to this end.

Methods:

We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through October 2018) to identify studies that reported on the performance of FCSEMS, BDS, and LAMS in the treatment of refractory benign GI strictures. Our goals were to evaluate the pooled rate of technical success, clinical success, and adverse events with these stents and compare the outcomes between them.

Results:

A total of 31 studies were analyzed. In total, 14 (342 patients), 11 (226 patients), and 8 studies (192 patients) reported the use of FCSEMS, BDS, and LAMS, respectively. The pooled rate of technical success was 96.5% [95% confidence interval (CI): 93.5-98.1], 91.9% (95% CI: 85.6-95.6), and 97.6% (95% CI: 94.0-99.0) with FCSEMS, BDS, and LAMS respectively. No statistical significance to the difference was noted. The pooled rate of clinical success was 48.4% (95% CI: 37.1-59.8), 34.9% (95% CI: 23.6-48.1), and 78.8% (95% CI: 65.8-87.8) with FCSEMS, BDS, and LAMS, respectively. Statistical significance was noted in LAMS versus FCSEMS (P=0.001) and LAMS versus BDS (P=0.001). LAMS demonstrated statistically better outcomes in regards to stent migration and postprocedure pain when compared with FCSEMS and BDS.

Conclusion:

Our study demonstrates that LAMS gives better clinical outcomes in the treatment of refractory benign GI strictures when compared with FCSEMS and BDS. Variability in the site, as well as the length of stricture, indirect comparison, and heterogeneity, were the limitations of our study.
Urothelial Carcinoma In Situ (CIS): New Insights
Authors: Akhtar Mohammed , Al-Bozom Issam A. , Ben Gashir Mohamed , Taha Noheir M. , Rashid Sameera , Al-Nabet Ajayeb D.M.H.
Published: May 2019

Urothelial carcinoma in situ (CIS) is a high-grade noninvasive malignancy with a high tendency of progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Urothelial CIS is histologically characterized by replacement of the urothelium by cells which fulfill the morphologic criteria of malignancy including nuclear pleomorphism, hyperchromasia, prominent nucleoli, and increased numbers of normal and abnormal mitoses. Urothelial CIS may be categorized as primary when it is not associated with any past or present urothelial carcinoma. It is termed as secondary when there is concomitant or previous urothelial carcinoma in the patient. In recent years detailed molecular studies have provided valuable data for intrinsic molecular subclassification of urothelial carcinoma into 2 broad categories namely luminal and basal types with significant implications for prognosis and therapy. Similar studies on urothelial CIS are limited but have provided crucial insight into the molecular basis of CIS. These studies have revealed that urothelial CIS may also be divided into luminal and basal subtypes, but luminal subtype is much more common. It has also been shown that in many cases, luminal type of urothelial CIS may undergo a class switch to basal type during progression to an invasive carcinoma. Additional studies may be required to confirm and further elaborate these findings.
Chyle Fat–Derived Stem Cells Conditioned Medium Inhibits Hypertrophic Scar Fibroblast Activity
Authors: Chen Junnan , Li Zhihua , Huang Zhenya , Liang Liming , Chen Minliang
Published: May 2019

Background

Hypertrophic scars (HSs) generally form after injury to the deep layers of the dermis and are characterized by excessive collagen deposition. An increasing amount of evidence has determined that human adipose tissue–derived mesenchymal stem cells attenuate fibrosis in various conditions. We explored the effect and possible mechanism of chyle fat–derived stem cells (CFSCs) on HS formation.

Methods

Hypertrophic scar–derived fibroblasts (HSFs) and CFSCs were isolated from individual patients. Third-passage CFSCs were isolated and cultured using a mechanical emulsification method, and their surface CD markers were analyzed by flow cytometry. The adipogenic and osteogenic differentiation capacity of the CFSCs was determined using oil red O staining and alizarin red S staining, respectively. Then, the effects of CFSCs on HSFs were assessed in vitro. Hypertrophic scar–derived fibroblasts were treated with starvation-induced conditioned medium from the CFSCs (CFSC-CM). The change in HSF cellular behaviors, such as cell proliferation, migration, and protein expression of scar-related molecules, was evaluated by cell counting assay, scratch wound assay, enzyme-linked immunosorbent assay, and western blotting. All data were analyzed using SPSS 17.0.

Results

The CFSCs expressed CD90, CD105, and CD73 but did not express CD34, CD45, or CD31. The CFSCs differentiated into adipocytes and osteoblasts under the appropriate induction conditions. Chyle fat–derived stem cells conditioned medium inhibited HSF proliferation and migration. The in vitro and ex vivo studies revealed that CFSC-CM decreased type I collagen, type III collagen, and α smooth muscle actin expression.

Conclusions

Our results suggest that CFSCs are associated with the inhibition of fibrosis in HSFs by a paracrine effect. The use of CFSC-CM may be a novel therapeutic strategy for HSs.
Quadruplex qPCR for qualitative and quantitative analysis of the HIV-1 latent reservoir
Authors: Gaebler Christian , Lorenzi Julio C. C. , Oliveira Thiago Y. , Nogueira Lilian , Ramos Victor , Lu Ching-Lan , Pai Joy A. , Mendoza Pilar , Jankovic Mila , Caskey Marina , Nussenzweig Michel C.
Published: May 2019

HIV-1 infection requires life-long therapy with anti-retroviral drugs due to the existence of a latent reservoir of transcriptionally inactive integrated proviruses. The goal of HIV-1 cure research is to eliminate or functionally silence this reservoir. To this end there are numerous ongoing studies to evaluate immunologic approaches including monoclonal antibody therapies. Evaluating the results of these studies requires sensitive and specific measures of the reservoir. Here we describe a relatively high throughput combined quantitative polymerase chain reaction (qPCR) and next generation sequencing method. Four different qPCR probes covering the packaging signal (PS), group-specific antigen (gag), polymerase (pol), and envelope (env) are combined in a single multiplex reaction to detect the HIV-1 genome in limiting dilution samples followed by sequence verification of individual reactions that are positive for combinations of any 2 of the 4 probes (Q4PCR). This sensitive and specific approach allows for an unbiased characterization of the HIV-1 latent reservoir.

HIV-1 cure research seeks to decrease or eliminate the latent reservoir. The evaluation of such curative strategies requires accurate measures of the reservoir. Gaebler et al. describe a combined multicolor qPCR and next generation sequencing method that enables the sensitive and specific characterization of the HIV-1 latent reservoir.
Risk taking to obtain reward: gender differences and associations with emotional and depressive symptoms in a nationally representative cohort of UK adolescents
Authors: Lewis Gemma , Srinivasam Ramya , Roiser Jonathan , Blakemore Sarah-Jayne , Flouri Eirini , Lewis Glyn
Published: May 2019

Background

Large population-based studies of neuropsychological factors that characterize or precede depressive symptoms are rare and we know little about gender differences in these associations.

Methods

The Millennium Cohort is a representative UK birth cohort of children born between 2000 and 2002. The Cambridge Gambling Task (CGT) was completed at ages 11 (n=12,355) and 14 (n=10,578). Our main exposure was proportion of points gambled, when odds of winning were above chance (risk taking to obtain reward). We also examined how much adolescents adjusted bets as odds of winning increased (risk adjustment). Outcomes were emotional symptoms at age 11 (SDQ) and depressive symptoms at age 14 (sMFQ). We calculated cross-sectional associations, and a longitudinal association from age 11 to 14, using linear regressions before and after adjusting for confounders.

Results

Females were less risk taking than males (e.g. females bet 9.22, 95% CI 8.65 to 9.80, percentage points lower at age 11). In univariable models there were cross-sectional associations between risk taking and emotional (age 11) or depressive (age 14) symptoms (e.g. at age 14, a 20-percentage point increase in risk taking was associated with a 0.52 reduction in sMFQ points, 95% CI -.71 to -.33). However, cross-sectional associations were explained by gender differences (at age 14 the association adjusted for gender was: .05, 95% CI -.15 to .25). Longitudinally, there was weak evidence of an association between risk taking and depressive symptoms in females only (a 20-point increase in risk taking at age 11 was associated with a reduction of 0.31 sMFQ points at age 14 (95% CI -.60 to -.02).

Conclusions

We found evidence that adolescent females were less likely to take risks than adolescent males. There was no strong evidence of an association between risk taking and emotional and depressive symptoms, after accounting for gender.

Abbreviations

CGT: Millennium Cohort Study (MCS); Cambridge Gambling Task (CGT); Strengths and Difficulties Questionnaire (SDQ); sMFQ: short Mood and Feelings Questionnaire.
The rodent vaginal microbiome across the estrous cycle and the effect of genital nerve electrical stimulation
Authors: Levy Micah , Bassis Christine M. , Kennedy Eric , Yoest Katie E. , Becker Jill B. , Bell Jason , Berger Mitchell B. , Bruns Tim M.
Published: May 2019

Treatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiota, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. In this study we used healthy rats, which are a common animal model for sexual function, however the rat vaginal microbiome is understudied. Thus this study also sought to examine the composition of the rat vaginal microbiota. Treatment rats (n=5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n=4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Analysis of 16S rRNA gene sequences was used to characterize the rat vaginal microbiota in baseline samples and determine the effect of stimulation. We found that the rat vaginal microbiota is dominated by Proteobacteria, Firmicutes, and Actinobacteria, which changed in relative abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear in these healthy rats, some Treatment animals had less alteration in microbiota composition between sequential samples than Control animals, suggesting that stimulation may help stabilize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.
Pooled CRISPR screening in pancreatic cancer cells implicates co-repressor complexes as a cause of multiple drug resistance via regulation of epithelial-to-mesenchymal transition
Authors: Ramaker Ryne C. , Hardigan Andrew A. , Gordon Emily R. , Wright Carter A. , Myers Richard M. , Cooper Sara J.
Published: May 2019

Pancreatic ductal adenocarcinoma (PDAC) patients suffer poor outcomes in part due to therapeutic resistance. We conducted four genome-wide CRISPR activation (CRISPRact) and CRISPR knock out (CRISPRko) screens to identify novel resistance mechanisms to four cytotoxic chemotherapies (gemcitabine, 5-fluorouracil, irinotecan, and oxaliplatin). ABCG2, a well-described efflux pump was the strongest mediator of resistance. We showed that overexpressing HDAC1 altered promoter occupancy and expression of genes involved in the epithelial-to-mesenchymal transition. Using the results of our CRISPR screens, we predicted drug sensitivity for patients and cell lines based on gene expression profiles. These predictions could be clinically useful for treatment selection.
Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes
Authors: Luppino Jennifer M. , Park Daniel S. , Nguyen Son C. , Lan Yemin , Xu Zhuxuan , Joyce Eric F.
Published: May 2019

The mammalian genome can be segmented into thousands of topologically associated domains (TADs) based on chromosome conformation capture studies, such as Hi-C. TADs have been proposed to act as insulated neighborhoods, spatially sequestering and insulating the enclosed genes and regulatory elements through chromatin looping and self-association. Recent results indicate that inter-TAD interactions can also occur, suggesting boundaries may be semi-permissible. However, the nature, extent, and function, if any, of these inter-TAD interactions remains unclear. Here, we combine super-and high-resolution microscopy with Oligopaint technology to precisely quantify the interaction frequency within and between neighboring domains in human cells. We find that intermingling across domain boundaries is a widespread feature of the human genome, with varying levels of interactions across different loci that correlate with their differing boundary strengths by Hi-C. Moreover, we find that cohesin depletion, which is known to abolish TADs at the population-average level, does not induce ectopic interactions but instead reduces both intra- and inter-domain interactions to a similar extent. Reduced chromatin intermixing due to cohesin loss affects domain incorporation and transcriptional bursting frequencies of genes close to architectural boundaries, potentially explaining the gene expression changes observed in the cohesinopathy Cornelia de Lange syndrome. Together, our results provide a mechanistic explanation for stochastic domain intermingling, arguing that cohesin partially bypasses boundaries to promote alternating incorporation of boundary-proximal genes into neighboring regulatory domains.
Patterns of annual and seasonal immune investment in a temporal reproductive opportunist
Authors: Schultz Elizabeth M. , Gunning Christian E. , Cornelius Jamie M. , Reichard Dustin G. , Klasing Kirk C. , Hahn Thomas P.
Published: May 2019

Historically, investigations of how organisms’ investments in immunity fluctuate in response to environmental and physiological changes have focused on seasonally breeding organisms that confine reproduction to seasons with mild environmental conditions and abundant resources. Consequently, knowledge of how harsh environmental conditions and reproductive effort may interact to shape investment in immunity remains limited. The red crossbill,Loxia curvirostra, is a songbird that can breed on both short, cold and long, warm days if conifer seeds are abundant. This species provides an ideal system to investigate the influence of environmental fluctuations, reproductive investment, and their potential interactions on patterns of immune investment. In this study, we measured inter- and intra-annual immune variation in crossbills across four consecutive summers (2010-2013) and multiple seasons within one year (summer 2011-spring 2012) to explore how physiological and environmental factors impact this immune variation. Overall, the data suggest that immunity varies seasonally, among years, and in response to environmental fluctuations in food resources, precipitation, and temperature, but less in response to physiological measures such as reproduction. Collectively, this system demonstrates that a reproductively flexible organism may breed when conditions allow simultaneous investment in survival-related processes rather than at the expense of them.
Transcriptomic insights into the establishment of coral-algal symbioses from the symbiont perspective
Authors: Mohamed Amin R , Andrade Natalia , Moya Aurelie , Chan Cheong Xin , Negri Andrew P. , Bourne David G. , Ball Eldon E , Miller David J
Published: May 2019

Despite the ecological significance of the mutualistic relationship between Symbiodiniaceae and reef-building corals, the molecular machinery underpinning the establishment of this relationship is not well understood. This is especially true of the symbiont side, as previous attempts to understand the interaction between coral larvae and Symbiodiniaceae have focused nearly exclusively on the host. In the current study, Acropora tenuis planula larvae were exposed to a compatible strain of Symbiodiniaceae (Cladocopium) and the transcriptomic landscape of the symbiont profiled at 3, 12, 48 and 72 h post-exposure using RNA-Seq. The transcriptomic response of Cladocopium to the symbiotic state was complex, the most obvious feature being an extensive and generalised downregulation of gene expression. Included in this “symbiosis-derived transcriptional repression” were a range of stress response and immune-related genes. In contrast, genes implicated in metabolism were upregulated in the symbiotic state. Consistent with previous ecological studies, this transcriptomic response of Cladocopium implied that active translocation of metabolites to the host occurred, and thus that the mutualistic relationship can be established at the larval stage. This study provides novel insights into the transcriptomic remodelling that occurs in Symbiodiniaceae, with important implications for understanding the establishment of symbiosis between corals and their dinoflagellate partners.