bluuebunny/crossref_metadata_2025 huggingface dataset:
Inequalities in the economic consequences of depression and anxiety in Europe: a systematic scoping review
Authors: Linder Anna , Gerdtham Ulf-G. , Trygg Nadja , Fritzell Sara , Saha Sanjib
Published: June 2019

Background

Depression and anxiety are associated with adverse outcomes in educational achievements and economic performances. Moreover, the prevalence of these disorders is unequally distributed among different population subgroups. Our objective is to investigate whether the economic consequences of depression and anxiety differ between population subgroups of different gender, socioeconomic status (SES), ethnicity and age, in Europe.

Methods

A systematic scoping literature review was performed to identify studies where exposure to depression or anxiety was identified at baseline and consequences in education, sickness absence, disability pension, unemployment and income/earnings were measured at follow-up.

Results

Seventeen articles were included in this review and most of these were conducted in the Nordic countries. The consequences of depression and anxiety were stratified by gender in most of the articles. However, only in a few studies, the findings were stratified by SES, age and ethnicity. The negative consequences of depression in educational performance, disability pension and income are larger for men compared to women. Moreover, low SES individuals have more depression- and anxiety-related absence from work than high SES individuals.

Conclusion

Our findings imply that the economic consequences of depression differ between population subgroups in Europe. This could have an impact on social stratification, shifting people who experience mental ill-health to lower SES groups or reinforcing an already disadvantaged position. More research is needed on unequal economic consequences of depression and anxiety in different population subgroups in Europe.
Predictive factors for non-participation or partial participation in breast, cervical and colorectal cancer screening programmes†
Authors: Dawidowicz Sébastien , Le Breton Julien , Moscova Laura , Renard Vincent , Bercier Sandrine , Brixi Zahida , Audureau Etienne , Clerc Pascal , Bastuji-Garin Sylvie , Ferrat Emilie
Published: June 2019

Background

No study has investigated factors associated with non-participation or partial participation in the different combination patterns of screening programmes for all three cancers, that is, breast, colorectal and cervical cancer.

Methods

In a retrospective cohort study, we sought to describe combinations of cancer screening participation rates among women in the Val-de-Marne area of France and to identify individual and contextual factors associated with non-participation or partial participation.

Results

Women aged between 50 and 65 and who were eligible for all three screening programmes (n = 102 219) were analysed in multilevel logistic models, with the individual as the Level 1 variable and the place of residence as the Level 2 variable. The women who did not participate in any of the screening programmes were 34.4%, whereas 30.1%, 24% and 11.5% participated in one, two or all three screening programmes, respectively. Age below 55, a previous false-positive mammography, prior opportunistic mammography only, no previous mammography, membership of certain health insurance schemes (all P < 0.05) and residence in a deprived area (P < 0.001) were independently associated with non-participation or partial participation. We observed a stronger effect of deprivation on non-participation in all three cancers than in combinations of screening programmes.

Conclusion

Our findings suggest that the health authorities should focus on improving cancer screenings in general rather than screenings for specific types of cancer, especially among younger women and those living in the most socially deprived areas.
Collaboration between the family nurse and family doctor from the perspective of patients: a qualitative study
Authors: Taranta Ewa , Marcinowicz Ludmila
Published: June 2019

Background

There is increasing focus on collaboration in primary health care, but there is insufficient patient perspective on collaboration between the family nurse and family doctor.

Objective

To explore how patients perceive collaboration between the family nurse and family doctor in primary health care in Poland.

Methods

A qualitative approach and an inductive, naturalistic inquiry strategy were used. Thirty-seven patients from eight general practice clinics in the north-eastern part of Poland participated in semi-structured, face-to-face interviews. The qualitative data were examined by means of thematic analysis. The study was reported according to the consolidated criteria for reporting qualitative research (COREQ) checklist.

Results

Four subthemes emerged in the context of nurse–doctor collaboration, namely: (i) carrying out the doctor’s orders; (ii) visit preparation; (iii) the family nurse as a source of information and (iv) participants’ perceptions of the status of the family nurse. Nurses performing instrumental activities connected with a doctor’s orders was understood by the participants to be collaboration and prevailed in their responses.

Conclusion

The perception of collaboration (or lack thereof) between the family nurse and family doctor results from patients’ varied experiences and observations during their visits to a primary care clinic. The traditional model of nursing care and the hierarchical relationship, in which the doctor has the dominant role, are evident in the patients’ remarks. The autonomy of nursing could be strengthened by expanding, and highlighting, the primary care activities that a nurse can perform on her own.
Individual-Level Antibody Dynamics Reveal Potential Drivers of Influenza A Seasonality in Wild Pig Populations
Authors: Pepin Kim M , Pedersen Kerri , Wan Xiu-Feng , Cunningham Fred L , Webb Colleen T , Wilber Mark Q
Published: June 2019

Swine are important in the ecology of influenza A virus (IAV) globally. Understanding the ecological role of wild pigs in IAV ecology has been limited because surveillance in wild pigs is often for antibodies (serosurveillance) rather than IAVs, as in humans and domestic swine. As IAV antibodies can persist long after an infection, serosurveillance data are not necessarily indicative of current infection risk. However, antibody responses to IAV infections cause a predictable antibody response, thus time of infection can be inferred from antibody levels in serological samples, enabling identification of risk factors of infection at estimated times of infection. Recent work demonstrates that these quantitative antibody methods (QAMs) can accurately recover infection dates, even when individual-level variation in antibody curves is moderately high. Also, the methodology can be implemented in a survival analysis (SA) framework to reduce bias from opportunistic sampling. Here we integrated QAMs and SA and applied this novel QAM–SA framework to understand the dynamics of IAV infection risk in wild pigs seasonally and spatially, and identify risk factors. We used national-scale IAV serosurveillance data from 15 US states. We found that infection risk was highest during January–March (54% of 61 estimated peaks), with 24% of estimated peaks occurring from May to July, and some low-level of infection risk occurring year-round. Time-varying IAV infection risk in wild pigs was positively correlated with humidity and IAV infection trends in domestic swine and humans, and did not show wave-like spatial spread of infection among states, nor more similar levels of infection risk among states with more similar meteorological conditions. Effects of host sex on IAV infection risk in wild pigs were generally not significant. Because most of the variation in infection risk was explained by state-level factors or infection risk at long-distances, our results suggested that predicting IAV infection risk in wild pigs is complicated by local ecological factors and potentially long-distance translocation of infection. In addition to revealing factors of IAV infection risk in wild pigs, our framework is broadly applicable for quantifying risk factors of disease transmission using opportunistic serosurveillance sampling, a common methodology in wildlife disease surveillance. Future research on the factors that determine individual-level antibody kinetics will facilitate the design of serosurveillance systems that can extract more accurate estimates of time-varying disease risk from quantitative antibody data.
Neighbourhood context and binge drinking from adolescence into early adulthood in a US national cohort
Authors: Fairman Brian J , Goldstein Risë B , Simons-Morton Bruce G , Haynie Denise L , Liu Danping , Hingson Ralph W , Gilman Stephen E
Published: June 2019

Background

Underage binge drinking is a serious health concern that is likely influenced by the neighbourhood environment. However, longitudinal evidence has been limited and few studies have examined time-varying neighbourhood factors and demographic subgroup variation.

Methods

We investigated neighbourhood influences and binge drinking in a national cohort of US 10th grade students at four times (2010–2014; n = 2745). We estimated odds ratios (OR) for past 30-day binge drinking associated with neighbourhood disadvantage, personal and property crime (quartiles), and number of liquor, beer and wine stores within 5 km, and then evaluated whether neighbourhood associations differ by age, sex and race/ethnicity.

Results

Neighbourhood disadvantage was associated with binge drinking before 18 [OR = 1.54; 95% confidence interval (1.14, 2.08)], but not after 18 years of age. Property crime in neighbourhoods was associated with a higher odds of binge drinking [OR = 1.54 (0.96, 2.45)], an association that was stronger in early adulthood [4th vs 1st quartile: OR = 1.77 (1.04, 3.03)] and among Whites [4th vs 1st quartile: OR = 2.46 (1.03, 5.90)]. Higher density of liquor stores predicted binge drinking among Blacks [1–10 stores vs none: OR = 4.31 (1.50, 12.36)] whereas higher density of beer/wine stores predicted binge drinking among Whites [one vs none for beer: OR = 2.21 (1.06, 4.60); for wine: OR = 2.04 (1.04, 4.03)].

Conclusions

Neighbourhood conditions, particularly those related to economic circumstances, crime and alcohol outlet density, were related to binge drinking among young adults, but associations varied across age and individual characteristics.
Compact Tori Associated to Hyperkähler Manifolds of Kummer Type
Authors: O’Grady Kieran G
Published: June 2019

Dedicato alla piccola Mia.

For $X$ a hyperkähler manifold of Kummer type, let $J^3(X)$ be the intermediate Jacobian associated to $H^3(X)$. We prove that $H^2(X)$ can be embedded into $H^2(J^3(X))$. We show that there exists a natural smooth quadric $Q(X)$ in the projectivization of $H^3(X)$, such that Gauss–Manin parallel transport identifies the set of projectivizations of $H^{2,1}(Y)$, for $Y$ a deformation of $X$, with an open subset of a linear section of $Q^{+}(X)$, one component of the variety of maximal linear subspaces of $Q(X)$. We give a new proof of a result of Mongardi restricting the action of monodromy on $H^2(X)$. Lastly, we show that if $X$ is projective, then $J^3(X)$ is an abelian fourfold of Weil type.
Relaxing non-interference requirements in parallel plans
Authors: Bofill Miquel , Espasa Joan , Villaret Mateu
Published: June 2019

The aim of being able to reason about quantities, time or space has been the main objective of the many efforts on the integration of propositional planning with extensions to handle different theories. Planning modulo theories (PMTs) are an approximation inspired by satisfiability modulo theories (SMTs) that generalize the integration of arbitrary theories with propositional planning. Parallel plans are crucial to reduce plan lengths and hence the time needed to reach a feasible plan in many approaches. Parallelization of actions relies on the notion of (non-)interference, which is usually determined syntactically at compile time. In this paper we define a semantic notion of interference between actions in PMT. Apart from being strictly stronger than any syntactic notion of interference, we show how semantic interference can be easily and efficiently checked by calling an off-the-shelf SMT solver at compile time, constituting a technique orthogonal to the solving method.
Trend on the protection of traditional knowledge associated with genetic resources within intellectual property chapters of Free Trade Agreements: the Peruvian experience
Authors: Ortega Sanabria Diego Francoise
Published: June 2019

During negotiations of Free Trade Agreements, the bargaining power of developed countries has pushed developing countries to yield to higher standards of intellectual property protection in exchange of commercial benefits. However, there is evidence that developing countries can also seek and ensure the adoption of measures aimed at safeguarding their legitimate interests as a result of these negotiations. An example is Peru, which has sought to ensure the inclusion of provisions to require patent applicants to disclose the origin of the genetic resources and the associated traditional knowledge when they are used in the development of an invention, as well as the presentation of the evidence as to the prior informed consent from their legitimate owners and the corresponding equitable benefit-sharing. This article seeks to analyze whether the terms finally adopted have had a real impact on the protection of the Peruvian traditional knowledge associated with genetic resources.
A unique case of ectopic pancreas presenting as jejunal malignance
Authors: Zhang Peng , Wang Mojin , Bai Lifen , Zhuang Wen
Published: June 2019

Ectopic pancreas is defined as pancreatic tissues having no anatomic or vascular connections with the orthotopic pancreas. It is difficult for clinicians to diagnose this disease without performing a histopathological examination because it lacks specific clinical manifestations. This case report is of a 46-year-old woman who presented with epigastric pain. She had elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4). Abdominal contrast-enhanced computed tomography (CT) revealed a persistently enhanced mass in the proximal jejunum, which was confirmed as ectopic pancreas via histopathological examination. Her serum CEA and CA72-4 levels were restored to normal ranges after resecting the jejunal ectopic pancreas. This is the first reported case of ectopic pancreas causing an elevation in serum CEA and CA-724 levels; this report supports the metaplasia theory and suggests that jejunal masses should be cautiously diagnosed for avoiding unnecessary concerns among patients and their families.
Mixed Phenotype Acute Leukemia that Evolved from Myelodysplastic Syndrome with Excess Blasts
Authors: Kim Miyoung , Zang Dae Young , Lee Jiwon , Park Ji-Young , Chung Yousun , Lee Young Kyung
Published: June 2019

Myelodysplastic syndrome (MDS) that evolves into acute leukemia with blasts of mixed phenotypes has rarely been reported and has no distinct diagnostic category. Herein, we describe a 79-year-old Korean female patient with MDS–excess blasts (MDS-EB) that evolved into acute leukemia; the blasts simultaneously expressed B-lymphoid and myeloid antigens. The patient was diagnosed with MDS-EB with blasts of myeloid lineage coexpressing a few B-lymphoid antigens with 7q and 20q abnormalities. The disease progressed to acute leukemia with blasts carrying more B-lymphoid antigens, which was immunophenotypically compatible with B-lymphoid/myeloid acute leukemia. Unlike previously reported patients whose blast populations are bilineal, our patient is the first with biphenotypic acute leukemia that progressed from MDS. The diagnosis of our patient introduces the possibility that many other types of biphenotypic acute leukemia may have gone undiagnosed and encourages hematologists to designate a specific diagnostic category for this type of disease, so that it can more readily be detected and studied in the future.
What Do People With Schizophrenia Do All Day? Ecological Momentary Assessment of Real-World Functioning in Schizophrenia
Authors: Granholm Eric , Holden Jason L , Mikhael Tanya , Link Peter C , Swendsen Joel , Depp Colin , Moore Raeanne C , Harvey Philip D
Published: June 2019

Schizophrenia is a major cause of disability worldwide. As new treatments for functioning are tested, the need grows to demonstrate real-world functioning gains. Ecological momentary assessment (EMA) may provide a more ecologically valid measure of functioning. In this study, smartphone-based EMA was used to signal participants with schizophrenia (N = 100) and controls (N = 71) 7 times a day for 7 days to respond to brief questionnaires about social interactions and functioning behaviors. Excellent adherence was found, with both groups completing an average of 85% of surveys and only 3% of participants with schizophrenia excluded for poor adherence. Four-week test–retest reliability was high (r = .83 for total productive behaviors). Relative to controls, participants with schizophrenia reported significantly less total productive activity (d = 1.2), fewer social interactions (d = 0.3), more nonproductive behaviors (d = 1.0; watching TV, resting), and more time at home (d = 0.8). Within the schizophrenia group, participants living independently showed better functioning on EMA relative to participants in supported housing (d = 0.8) and participants engaged in vocational activities showed better functioning than individuals not engaged in vocational activities (d = 0.55). Modest correlations were found between EMA and an in-lab self-report measure of functioning activities performed in the community, but not between EMA and measures of functional capacity or potential. This study demonstrated the feasibility, sensitivity reliability, and validity of EMA methods to assess functioning in schizophrenia. EMA provides a much-needed measure of what individuals with schizophrenia are actually doing in real-world contexts. These results also suggest that there may be important disjunctions between indices of abilities and actual real-world functioning.
Decontamination and Management of Contaminated Hair following a CBRN or HazMat Incident
Authors: Matar Hazem , Pinhal Andreia , Amer Nevine , Barrett Mark , Thomas Elliot , Hughes Philip , Larner Joanne , Chilcott Robert P
Published: June 2019

This in vitro study evaluated the “triple protocol” of dry decontamination, the ladder pipe system (a method for gross decontamination), and technical decontamination for the decontamination of hair following chemical contamination. First, we assessed the efficacy of the 3 protocols, alone or in combination, on excised porcine skin and human hair contaminated with either methyl salicylate (MS), phorate (PHR), sodium fluoroacetate (SFA), or potassium cyanide (KCN). A second experiment investigated the residual hair contamination following decontamination with the triple protocol at different intervals postexposure. In a third experiment, hair decontaminated after exposure to MS or PHR was evaluated for off-gassing. Though skin decontamination was highly effective, a substantial proportion (20%–40%) of the lipophilic compounds (MS and PHR) remained within the hair. The more water-soluble contaminants (SFA and KCN) tended to form much smaller reservoirs within the hair. Interestingly, substantial off-gassing of MS, a medium volatility chemical, was detectable from triple-decontaminated hair up to 5 days postexposure. Overall, the decontamination strategies investigated were effective for the decontamination of skin, but less so for hair. These findings highlight the importance of contaminated hair serving as a source of potential secondary contamination by contact or inhalation. Therefore, consideration should be given to the removal of contaminated hair following exposure to toxic chemicals.
The Normative Impact of Invoking Directives: Casting Light on Direct Effect and the Elusive Distinction between Obligations and Mere Adverse Repercussions
Authors: Squintani Lorenzo , Lindeboom Justin
Published: June 2019

The main aim of this paper is to cast light on the case law on direct effect of directives, which has remained elusive to both scholars and practitioners. To this end, we first revisit the relevant case law on inverse vertical, horizontal. and triangular disputes to show that the fundamental distinction drawn by the case law is that between ‘direct obligations’ and ‘mere adverse repercussions’. Subsequently, we propose a doctrinal approach to distinguish between ‘direct obligations’ and ‘mere adverse repercussions’ which centres on the impact of invoking a Euorpean Union (EU) directive on the norms governing the dispute. This ‘normative impact theory’ explains all existing case law on the direct effect of directives, and thus aids a better understanding of the concept of imposing obligations on individuals. We compare this theory with other doctrinal theories that have purported to explain the case law, including the well-known distinction between invocabilité de substitution and invocabilité d’exclusion, concluding that the normative impact theory has descriptive and normative advantages over existing approaches. Lastly, we show how the functioning of the preliminary reference procedure has affected the development of the case law on direct effect. We demonstrate that the European Court of Justice (ECJ) applies a presumption that consistent interpretation is capable of remedying incompatibilities between national and EU law. Secondly, we show how the formulation of the preliminary reference can substantially affect, and even confuse, the answer of the ECJ as regards matters of direct effect.
Evaluation of Oxathiapiprolin for the Management of Sunflower Downy Mildew
Authors: Humann Ryan M. , Johnson Keith D. , Wunsch Michael J. , Meyer Scott M. , Jordahl James G. , Bauske Elizabeth C. , Halvorson Jessica M. , Friskop Andrew J. , O’Bryan Keith A. , Gulya Thomas J. , Markell Samuel G.
Published: June 2019

Downy mildew is a yield-limiting disease of sunflower, caused by the pathogen Plasmopara halstedii. Zoospore infection of root tissue shortly after planting results in systemic infection, causing postemergence damping off or severe stunting and head sterility. Although fungicide-applied seed treatments can be an effective management tool, the pathogen is resistant to phenylamide fungicides in many growing regions, and other available fungicides have limited efficacy. Oxathiapiprolin, the first member of the piperidinyl thiazole isoxazoline fungicides, was evaluated for efficacy on downy mildew in field trials conducted from 2011 to 2015 in North Dakota. Throughout the course of the study, the rate range was narrowed from active ingredient (a.i.) at 0.45 to 116.0 µg a.i. seed−1 to an optimal effective rate of 9.37 to 18.75 µg a.i. seed−1. Within that optimal range, the downy mildew incidence of sunflower planted with oxathiapiprolin-treated seed was significantly lower than the incidence in the nontreated sunflower in all 11 trials with disease pressure. Additionally, downy mildew incidence of sunflower planted with oxathiapiprolin-treated seed was significantly lower than sunflower planted with competitive commercially available fungicide-treated seed in 10 of those 11 trials. The use of oxathiapiprolin by sunflower growers is likely to reduce disease incidence and subsequent yield loss to downy mildew.
Discharge Readiness after Propofol with or without Dexmedetomidine for Colonoscopy
Authors: Edokpolo Leonard U. , Mastriano Daniel J. , Serafin Joanna , Weedon Jeremy C. , Siddiqui Maryam T. , Dimaculangan Dennis P.
Published: June 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Enhanced recovery protocols employ various approaches to minimize detrimental side effects of anesthetizing agents. The authors tested the hypothesis that adding low-dose dexmedetomidine to propofol for anesthesia in ambulatory colonoscopies, compared with propofol alone, would lower the propofol requirement, improve the intra-procedure hemodynamic state, and not increase time-to-discharge.

Methods

In this noninferiority, double-blind, randomized controlled trial, patients having colonoscopies received total IV anesthesia either with propofol and placebo (n = 50), or propofol and a bolus dose of dexmedetomidine, 0.3 μg/kg (n = 51). Additional propofol was administered to maintain a Bispectral Index score of 60. Following the procedure, readiness for discharge was assessed regularly using the Modified Post Anesthetic Discharge Scoring System until discharge criteria were met. The primary outcome was the percentage of patients meeting discharge criteria within 30 min from procedure end-time.

Results

Twenty-six of 51 (51%) patients receiving propofol-dexmedetomidine were ready for discharge by 30 min from procedure end time, compared with 44 of 50 (88%) receiving propofol (P < 0.001). Propofol consumption was lower in subjects receiving propofol–dexmedetomidine (140 μg · kg-1 · min-1) compared to those receiving propofol (180 μg · kg-1 · min-1) with P = 0.011. The lowest mean arterial pressure decreased further from baseline in those receiving propofol–dexmedetomidine (−30%; mean decrease −30 ±10.5 mmHg) compared to propofol (−21%; mean decrease, −22 ± 14.2 mmHg) with P = 0.003. There was no difference in incidence of bradycardia, with sustained bradycardia occurring in 3 of 51 (6%) patients receiving propofol–dexmedetomidine compared to 1 of 50 (2%) patients receiving propofol (P = 0.62). No apnea episodes requiring positive-pressure ventilation occurred in either group.

Conclusions

For anesthesia in ambulatory colonoscopy, combining low-dose dexmedetomidine with propofol delayed discharge readiness and provoked hypotension compared to propofol alone.
Discovering Pain in Newborn Infants
Authors: Anand Kanwaljeet J. S.
Published: June 2019

Randomised Trial of Fentanyl Anesthesia in Preterm Babies Undergoing Surgery: Effects on the Stress Response. By Anand KJ, Sippell WG, and Aynsley-Green A. Lancet 1987; 1:243–8. Reprinted with permission.

In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 μg/kg intravenously) to the anesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the nonfentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the nonfentanyl group on the second and third postoperative days. Compared with the fentanyl group, the nonfentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anesthesia may be associated with an improved postoperative outcome.
Mantle cell lymphoma in patients not eligible for autologous stem cell transplantation
Authors: Aurer Igor
Published: June 2019

Purpose of review

Mantle cell lymphoma (MCL) is a disease predominantly affecting elderly patients with bad prognosis. Recently, a number of new agents have been shown to be active in this disease. This article reviews this data from the standpoint of everyday practice.

Recent findings

Front-line regimens combining rituximab with CHOP, cytarabine, bendamustine or lenalidomide, frequently followed by rituximab maintenance, remain the standard. Choice depends on the aggressiveness of the disease, patient characteristics and local availability. BTK inhibitors have emerged as most important agents for the treatment of relapsed/refractory disease, but many other options exist, including rituximab, chemotherapy, immunomodulators, bortezomib and venetoclax that can be used in combination and sequentially. In frail patients, combinations of rituximab with low-intensity chemotherapy, immunomodulators and BTK inhibitors can be useful but care must be taken to avoid additive drug toxicities and interaction.

Recent advances in treatment of MCL enable the delivery of multiple lines of therapy resulting in prolonged survival in most patients. Results of treatment of blastoid MCL with high Ki67 remain unsatisfactory and are an unmet medical need.
Evaluation of a Deep Learning System For Identifying Glaucomatous Optic Neuropathy Based on Color Fundus Photographs
Authors: Al-Aswad Lama A. , Kapoor Rahul , Chu Chia Kai , Walters Stephen , Gong Dan , Garg Aakriti , Gopal Kalashree , Patel Vipul , Sameer Trikha , Rogers Thomas W. , Nicolas Jaccard , De Moraes Gustavo C. , Moazami Golnaz
Published: June 2019

Precis:

Pegasus outperformed 5 of the 6 ophthalmologists in terms of diagnostic performance, and there was no statistically significant difference between the deep learning system and the “best case” consensus between the ophthalmologists. The agreement between Pegasus and gold standard was 0.715, whereas the highest ophthalmologist agreement with the gold standard was 0.613. Furthermore, the high sensitivity of Pegasus makes it a valuable tool for screening patients with glaucomatous optic neuropathy.

Purpose:

The purpose of this study was to evaluate the performance of a deep learning system for the identification of glaucomatous optic neuropathy.

Materials and Methods:

Six ophthalmologists and the deep learning system, Pegasus, graded 110 color fundus photographs in this retrospective single-center study. Patient images were randomly sampled from the Singapore Malay Eye Study. Ophthalmologists and Pegasus were compared with each other and to the original clinical diagnosis given by the Singapore Malay Eye Study, which was defined as the gold standard. Pegasus’ performance was compared with the “best case” consensus scenario, which was the combination of ophthalmologists whose consensus opinion most closely matched the gold standard. The performance of the ophthalmologists and Pegasus, at the binary classification of nonglaucoma versus glaucoma from fundus photographs, was assessed in terms of sensitivity, specificity and the area under the receiver operating characteristic curve (AUROC), and the intraobserver and interobserver agreements were determined.

Results:

Pegasus achieved an AUROC of 92.6% compared with ophthalmologist AUROCs that ranged from 69.6% to 84.9% and the “best case” consensus scenario AUROC of 89.1%. Pegasus had a sensitivity of 83.7% and a specificity of 88.2%, whereas the ophthalmologists’ sensitivity ranged from 61.3% to 81.6% and specificity ranged from 80.0% to 94.1%. The agreement between Pegasus and gold standard was 0.715, whereas the highest ophthalmologist agreement with the gold standard was 0.613. Intraobserver agreement ranged from 0.62 to 0.97 for ophthalmologists and was perfect (1.00) for Pegasus. The deep learning system took ∼10% of the time of the ophthalmologists in determining classification.

Conclusions:

Pegasus outperformed 5 of the 6 ophthalmologists in terms of diagnostic performance, and there was no statistically significant difference between the deep learning system and the “best case” consensus between the ophthalmologists. The high sensitivity of Pegasus makes it a valuable tool for screening patients with glaucomatous optic neuropathy. Future work will extend this study to a larger sample of patients.
A Comparison of Quadriceps Tendon Autograft With Bone-Patellar Tendon-Bone Autograft and Hamstring Tendon Autograft for Primary Anterior Cruciate Ligament Reconstruction: A Systematic Review and Quantitative Synthesis
Authors: Ajrawat Prabjit , Dwyer Tim , Whelan Daniel , Theodoropoulos John , Murnaghan Lucas , Bhargava Manoj , Ogilvie-Harris Darrell , Chahal Jaskarndip
Published: June 2019

Objective:

There is growing enthusiasm for the increased use of quadriceps tendon (QT) autograft for primary anterior cruciate ligament reconstruction (ACLR). The purpose of this analysis was to synthesize and quantitatively assess the available evidence comparing QT autograft with hamstring tendon (HT) and bone-patellar tendon-bone (BPTB) autografts, regarding functional outcomes, knee stability, anterior knee pain, and revision rates.

Data Sources:

A search in MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials for eligible studies up to May 2018 was conducted. Two reviewers selected studies based on inclusion criteria and assessed methodological quality. Outcomes analyzed were anterior knee pain, graft failure rates, knee stability, functional outcomes, and adverse events. Pooled analyses were performed for continuous and dichotomous variables where appropriate.

Main Results:

Ten studies (1 randomized trial and 9 nonrandomized cohorts) met our inclusion criteria, which included 1398 patients. The analysis showed no statistical difference in anterior knee pain when comparing QT and HT autografts, but a significant difference between QT and BPTB autografts [odds ratio, 0.15 (95% confidence interval, 0.08-0.27); P < 0.001]. There were no differences between all 3 autografts in revision rates, knee stability, and patient-reported functional outcomes.

Conclusions:

Quadriceps tendon autograft is a suitable graft alternative for primary ACLR, as it achieves good clinical outcomes with a low incidence of anterior knee pain. Given the limited quality of the included studies, there is a need for a well-designed multicenter randomized control trial comparing QT autograft with other primary ACL autografts to confirm our findings.

Level of Evidence:

Level IV systematic review.
Designing gene drives to limit spillover to non-target populations
Authors: Greenbaum Gili , Feldman Marcus W. , Rosenberg Noah A. , Kim Jaehee
Published: June 2019

The prospect of utilizing CRISPR-based gene-drive technology for controlling populations, such as invasive and disease-vector species, has generated much excitement. However, the potential for spillovers of gene drive alleles from the target population to non-target populations — events that may be ecologically catastrophic — has raised concerns. Here, using two-population mathematical models, we investigate the possibility of limiting spillovers and impact on non-target populations by designing differential-targeting gene drives, in which the expected equilibrium gene drive allele frequencies are high in the target population but low in the non-target population. We find that achieving differential targeting is possible with certain configurations of gene drive parameters. Most of these configurations ensure differential targeting only under relatively low migration rates between target and non-target populations. Under high migration, differential targeting is possible only in a narrow region of the parameter space. When migration is increased, differential-targeting states can sharply transition to states of global fixation or global loss of the gene drive. Because fixation of the gene drive in the non-target population could severely disrupt ecosystems, we outline possible ways to avoid this outcome. Our results emphasize that, although gene drive technology is promising, understanding the potential consequences for populations other than the targets requires detailed analysis of gene-drive spillovers, and that ways to limit the unintended effects of gene drives to non-target populations should be explored prior to the application of gene drives in natural settings.
Sinoseris (Crepidinae, Cichorieae, Asteraceae), a new genus endemic to China of three species, two of them new to science
Authors: Wang Ze-Huan , Kilian Norbert , Chen Ya-Ping , Peng Hua
Published: June 2019

Elucidating the systematic position of two Chinese species described originally as Lactuca hirsuta and L. scandens, of which only historical specimens from the late 19th and early 20th century were known, field work confirmed the occurrence of three different species. Molecular phylogenetic analysis of these species based on sequences of the nuclear ribosomal internal transcribed spacer (nrITS) region uncovered a hitherto unknown lineage in a phylogenetic backbone of the subtribe Crepidinae of the sunflower family tribe Cichorieae. Substantiated by comparative morphological studies, this lineage is described as genus new to science, named Sinoseris, endemic to the Chinese provinces Sichuan and Yunnan. Two of its three species are new to science, while the third is conspecific with both L. hirsuta and L. scandens.
Deriving Disease Modules from the Compressed Transcriptional Space Embedded in a Deep Auto-encoder
Authors: Dwivedi Sanjiv K. , Tjärnberg Andreas , Tegnér Jesper , Gustafsson Mika
Published: June 2019

Disease modules in molecular interaction maps have been useful for characterizing diseases. Yet biological networks, commonly used to define such modules are incomplete and biased toward some well-studied disease genes. Here we ask whether disease-relevant modules of genes can be discovered without assuming the prior knowledge of a biological network. To this end we train a deep auto-encoder on a large transcriptional data-set. Our hypothesis is that such modules could be discovered in the deep representations within the auto-encoder when trained to capture the variance in the input-output map of the transcriptional profiles. Using a three-layer deep auto-encoder we find a statistically significant enrichment of GWAS relevant genes in the third layer, and to a successively lesser degree in the second and first layers respectively. In contrast, we found an opposite gradient where a modular protein-protein interaction signal was strongest in the first layer but then vanishing smoothly deeper in the network. We conclude that a data-driven discovery approach, without assuming a particular biological network, is sufficient to discover groups of disease-related genes.
miR-92a-3p controls cell cycle progression in zebrafish
Authors: Presslauer Christopher E. , Bizuayehu Teshome T. , Fernandes Jorge M.O. , Babiak Igor S.
Published: June 2019

Biological functions of micro RNAs (miRNAs) in the early stages of vertebrate development remain largely unknown. In zebrafish, miRNA miR-92a-3p is abundant in the germ cells throughout gonadal development, as well as in ovulated oocytes. Previously, we demonstrated that inhibition of miR-92a-3p in mature ovaries resulted in developmental arrest at the 1-cell stage upon fertilization of the affected oocytes. This suggested functions of miR-92a-3p in early development. In the present study, we identified wee2, an oocyte-specific protein tyrosine kinase, as a target of maternal miR-92a-3p during the early stages of zebrafish embryogenesis. Spatiotemporal co-presence of both miR-92a-3p and wee2 during early embryo development was confirmed by absolute quantification and in situ hybridization. Targeted knockdown of miR-92a-3p in embryos resulted in retarded embryonic development over the first 24 hours. Target validation assays demonstrated that miR-92a-3p interacted with the predicted wee2 3’UTR binding site, which was strongly suppressed by endogenous miR-92a-3p. Our results suggest that miR-92a-3p regulates the abundance of wee2, a cyclin-dependent kinase 1 inhibitor, thus having important role in regulation of the cell cycle during cleavage stages in zebrafish.

Summary statement

In zebrafish, maternal miR-92a-3p was demonstrated to suppress translation of wee2, a cyclin-dependent kinase 1 inhibitor which regulates cell cycle progression during the early stages of embryogenesis.
5-Fluorouracil treatment induces characteristic T>G mutations in human cancer
Authors: Christensen Sharon , Van der Roest Bastiaan , Besselink Nicolle , Janssen Roel , Boymans Sander , Martens John , Yaspo Marie-Laure , Priestley Peter ,   Center for Personalized Cancer Treatment, Kuijk Ewart , Cuppen Edwin , Van Hoeck Arne
Published: June 2019

5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. It is proposed that 5-FU possesses anticancer properties via the interference with nucleotide synthesis and incorporation into DNA. As both mechanisms may have a mutational impact on both surviving tumor and healthy cells, we treated intestinal organoids with 5-FU followed by whole genome sequencing analysis and uncovered a highly characteristic mutational pattern that is dominated by T>G substitutions in a CTT context. Analysis of tumor whole genome sequencing data confirmed that this signature can also be identified in vivo in colorectal and breast cancer patients that have undergone treatment with 5-FU. We also found that more 5-FU mutations are induced in TP53 null backgrounds which may be of clinical relevance. Taken together, our results demonstrate that 5-FU is mutagenic and may drive tumor evolution and increase the risk of secondary malignancies. Furthermore, the identified signature shows a strong resemblance to COSMIC signature 17, the hallmark signature of treatment-naive esophageal and gastric tumors, which indicates that distinct endogenous and exogenous triggers can converge onto highly similar mutational signatures.
Grid cells encode local head direction
Authors: Gerlei Klara , Passlack Jessica , Hawes Ian , Vandrey Brianna , Stevens Holly , Papastathopoulos Ioannis , Nolan Matthew F.
Published: June 2019

Grid and head direction codes represent cognitive spaces for navigation and memory. Pure grid cells generate grid codes that have been assumed to be independent of head direction, whereas conjunctive cells generate grid representations that are tuned to a single head direction. Here, we demonstrate that pure grid cells also encode head direction, but through distinct mechanisms. We show that individual firing fields of pure grid cells are tuned to multiple head directions, with the preferred sets of directions differing between fields. This local directionality is not predicted by previous continuous attractor or oscillatory interference models of grid firing but is accounted for by models in which pure grid cells integrate inputs from co-aligned conjunctive cells with firing rates that differ between their fields. Local directional signals from grid cells may contribute to downstream computations by decorrelating different points of view from the same location.
STING recruits NLRP3 to the ER and deubiquitinates NLRP3 to activate the inflammasome
Authors: Wang Wenbiao , Hu Dingwen , Feng Yuqian , Wu Caifeng , Li Aixin , Wang Yingchong , Cheng Keli , Tian Mingfu , Xiao Feng , Zhang Qi , Shereen Muhammad Adnan , Chen Weijie , Pan Pan , Wan Pin , Liu Weiyong , Liu Fang , Wu Kailang , Li Geng , Liu Yingle , Wu Jianguo
Published: June 2019

One of the fundamental reactions of the innate immune responses to pathogen infection is the release of pro-inflammatory cytokines, including IL-1β, processed by the NLRP3 inflammasome. STING is essential for innate immune responses and inflammasome activation. Here we reveal a distinct mechanism by which STING regulates the NLRP3 inflammasome activation, IL-1β secretion, and inflammatory responses in human cell lines, mice primary cells, and mice. Interestingly, upon HSV-1 infection and cytosolic DNA stimulation, STING binds to NLRP3 and promotes the inflammasome activation through two approaches. First, STING recruits NLRP3 and promotes NLRP3 translocation to the endoplasmic reticulum, thereby facilitating the inflammasome formation. Second, STING interacts with NLRP3 and removes K48- and K63-linked polyubiquitination of NLRP3, thereby promoting the inflammasome activation. Collectively, we demonstrate that the cGAS-STING-NLRP3 signaling is essential for host defense against DNA virus infection.
Gaze and Movement Assessment (GaMA): Inter-site validation of a visuomotor upper limb functional protocol
Authors: Williams Heather E. , Chapman Craig S. , Pilarski Patrick M. , Vette Albert H. , Hebert Jacqueline S.
Published: June 2019

Background

Successful hand-object interactions require precise hand-eye coordination with continual movement adjustments. Quantitative measurement of this visuomotor behaviour could provide valuable insight into upper limb impairments. The Gaze and Movement Assessment (GaMA) was developed to provide protocols for simultaneous motion capture and eye tracking during the administration of two functional tasks, along with data analysis methods to generate standard measures of visuomotor behaviour. The objective of this study was to investigate the reproducibility of the GaMA protocol across two independent groups of non-disabled participants, with different raters using different motion capture and eye tracking technology.

Methods

Twenty non-disabled adults performed the Pasta Box Task and the Cup Transfer Task. Upper body and eye movements were recorded using motion capture and eye tracking, respectively. Measures of hand movement, angular joint kinematics, and eye gaze were compared to those from a different sample of twenty non-disabled adults who had previously performed the same protocol with different technology, rater and site.

Results

Participants took longer to perform the tasks versus those from the earlier study, although the relative time of each movement phase was similar. Measures that were dissimilar between the groups included hand distances travelled, hand trajectories, number of movement units, eye latencies, and peak angular velocities. Similarities included all hand velocity and grip aperture measures, eye fixations, and most peak joint angle and range of motion measures.

Discussion

The reproducibility of GaMA was confirmed by this study, despite a few differences introduced by learning effects, task demonstration variation, and limitations of the kinematic model. The findings from this study provide confidence in the reliability of normative results obtained by GaMA, indicating it accurately quantifies the typical behaviours of a non-disabled population. This work advances the consideration for use of GaMA in populations with upper limb sensorimotor impairment.
Do atmospheric events explain the arrival of an invasive ladybird (Harmonia axyridis) in the UK?
Authors: Siljamo Pilvi , Ashbrook Kate , Comont Richard F. , Skjøth Carsten Ambelas
Published: June 2019

Species introduced outside their natural range threaten global biodiversity and despite greater awareness of invasive species risks at ports and airports, control measures in place only concern anthropogenic routes of dispersal. Here, we use the Harlequin ladybird,Harmonia axyridis, an invasive species which first arrived in the UK from continental Europe in 2003, to test whether records from 2004 and 2005 were associated with atmospheric events. We used the atmospheric dispersion model SILAM to model the movement of this species from known distributions in continental Europe and tested whether the predicted atmospheric events were associated with the frequency of ladybird records in the UK. We show that the distribution of this species in the early years of its arrival does not provide substantial evidence for a purely anthropogenic introduction and show instead that atmospheric events can better explain this invasion event. Our results suggest that air flows which may assist dispersal over the English Channel are relatively frequent; ranging from once a week from Belgium and the Netherlands to 1-2 times a week from France over our study period. Given the frequency of these events, we demonstrate that atmospheric-assisted dispersal is a viable route for flying species to cross natural barriers.