High-throughput analysis suggests differences in journal false discovery rate by subject area and impact factor but not open access status.

BACKGROUND: A low replication rate has been reported in some scientific areas motivating the creation of resource intensive collaborations to estimate the replication rate by repeating individual studies. The substantial resources required by these projects limits the number of studies that can be repeated and consequently the generalizability of the findings. We extend the use of a method from Jager and Leek to estimate the false discovery rate for 94 journals over a 5-year period using p values from over 30,000 abstracts enabling the study of how the false discovery rate varies by journal characteristics. RESULTS: We find that the empirical false discovery rate is higher for cancer versus general medicine journals (p = 9.801E-07, 95% CI: 0.045, 0.097; adjusted mean false discovery rate cancer = 0.264 vs. general medicine = 0.194). We also find that false discovery rate is negatively associated with log journal impact factor. A two-fold decrease in journal impact factor is associated with an average increase of 0.020 in FDR (p = 2.545E-04). Conversely, we find no statistically significant evidence of a higher false discovery rate, on average, for Open Access versus closed access journals (p = 0.320, 95% CI - 0.015, 0.046, adjusted mean false discovery rate Open Access = 0.241 vs. closed access = 0.225). CONCLUSIONS: Our results identify areas of research that may need additional scrutiny and support to facilitate replicable science. Given our publicly available R code and data, others can complete a broad assessment of the empirical false discovery rate across other subject areas and characteristics of published research.

The impact of airborne pollution on atopic dermatitis: a literature review.

The increasing prevalence of atopic dermatitis (AD) parallels a global rise in industrialization and urban living over recent decades. This shift in lifestyle is accompanied by greater cutaneous exposure to environmental pollutants during the course of daily activities. The objectives of this review are to highlight the effects of airborne pollution on epidermal barrier function, examine evidence on the relationship between pollutants and AD, synthesize a proposed mechanism for pollution-induced exacerbation of AD, and identify potential methods for the reduction and prevention of pollutant-induced skin damage. The literature review was done by searching the PubMed, Embase and Google Scholar databases. Inclusion criteria were in vitro and animal studies, clinical trials and case series. Non-English-language publications, review articles and case reports were excluded. Pollutants induce cutaneous oxidative stress and have been shown to damage skin barrier integrity by altering transepidermal water loss, inflammatory signalling, stratum corneum pH and the skin microbiome. AD represents a state of inherent barrier dysfunction, and both long- and short-term pollutant exposure have been linked to exacerbation of AD symptoms and increased AD rates in population studies. Airborne pollutants have a detrimental effect on skin barrier integrity and AD symptoms, and appear to pose a multifaceted threat in AD through several parallel mechanisms, including oxidative damage, barrier dysfunction, immune stimulation and propagation of the itch-scratch cycle. Future research is needed to elucidate specific mechanisms of pollution-induced epidermal barrier dysfunction and to identify efficacious methods of skin barrier repair and protection against pollutant-driven damage.

Prognostic relevance of topoisomerase II α and minichromosome maintenance protein 6 expression in colorectal cancer.

BACKGROUND: Despite rising incidence rates of colorectal malignancies, only a few prognostic tools have been implemented in proven clinical routine. Cell division and proliferation play a significant role in malignancies. In terms of colorectal cancer, the impact of proliferation associated proteins is controversially debated. The aim of our study was to examine the expression of topoisomerase II α and minichromosome maintenance protein 6 and to correlate these findings with the clinical data. METHODS: Tissue samples of 619 patients in total were stained using the antibodies Ki-S4 and Ki-MCM6 targeting topoisomerase II α as well as minichromosome maintenance protein 6. The median rate of proliferation was correlated with clinical and follow up data. RESULTS: The expression rate of minichromosome maintenance protein 6 is significantly higher than the proportion of topoisomerase II α in tumour cells (p < 0.001). A high expression of both proteins coincides with a beneficial outcome for the patient, indicating a favourable prognostic marker (p < 0.001 and p = 0.008). CONCLUSIONS: We have demonstrated that high expression rates of proliferative markers is linked to a beneficial patient outcome. According to the general opinion, a high expression rate correlates with a poor patient outcome. In this study, we were able to refute this assertion.

Fully robotic da Vinci Ivor-Lewis esophagectomy in four-arm technique-problems and solutions.

The aim of this technical note is a step-by-step description of a fully robotic abdominothoracic esophagectomy with an intrathoracic esophagogastrostomy. We report on our technique and short-term results of 75 patients undergoing an Ivor-Lewis esophagectomy using a fully robotic 4-arm approach in the abdominal and thoracic phase with a hand-sewn intrathoracic anastomosis. There are several important steps and differences to consider compared to the conventional minimal invasive approach (patient's positioning, anaesthesiological set up, port placement, gastric conduit pull up, technique of esophagostrostomy). Mean operative time was 392 minutes (240-610) with a 94% R0 resection status. Conversion to open procedure occurred in 2 (2.6%) in the abdominal, and 14 (18.2%) in the thoracic phase. Main reasons for conversion were problems during the lifting of the gastric conduit and difficulties in the construction of the esophagogastrostomy. The rate dropped during the last 20 patients (1/20 (10%). Our results suggest that the reported technique is safe and feasible. It satisfies the oncological principles and provides the advantages of robotic assisted minimal invasive surgery.

Transverse sectioning in the evaluation of skin biopsy specimens from alopecic dogs.

OBJECTIVES: Transverse sectioning of skin biopsy specimens has revolutionised assessment of human alopecia by demonstration of every hair in each specimen, allowing quantitative evaluation of follicular activity. Since only vertical sectioning is performed routinely in veterinary laboratories, we aimed to determine whether transverse sectioning was a valuable technique in assessment of canine alopecia. METHODS: Paired vertical and transverse sections of biopsy specimens from 31 alopecic dogs were examined independently in triplicate in random order and blinded to previous diagnosis using a standard check-list proforma. Assessments of key features (follicular activity [anagen/telogen], infundibular hyperkeratosis, sebaceous gland abnormalities, pigment clumping, dermal inflammation) by each sectioning method were compared. RESULTS: In the 31 cases, (atrophic [n = 13], dysplastic [n = 12], inflammatory diseases [n = 6]), follicular inactivity scores (median, [lower-upper quartile]) in transverse sections significantly exceeded those in vertical sections (transverse 4 [3-5], vertical 3 [2-4]). Agreement between the two sectioning planes was moderate for infundibular hyperkeratosis (kappa = 0.5210) and dermal inflammation (0.4351), fair for sebaceous gland abnormalities (0.3966) and pigment clumping (0.2197), but slight for follicular activity (0.1041). Vertical sectioning demonstrated diagnostically important epidermal pathology (n = 2) and dermal thinning (n = 3) whereas transverse sectioning enhanced assessment of hair growth phase (n = 11), follicular structure and architecture (n = 11), and focal luminal or mural folliculitides (n = 3). CLINICAL SIGNIFICANCE: Transverse sectioning confers significant benefits and complements traditional vertical sectioning in the histological assessment of canine hair follicle diseases, particularly when subtle abnormalities comprise distorted compound follicle architecture, hair cycle arrest or when relatively few adnexal structures are affected.

Juvenile-onset and adult-onset demodicosis in dogs in the UK: prevalence and breed associations.

OBJECTIVES: To explore epidemiological features of demodicosis relevant to UK veterinary general practitioners. Breed risk factors were proposed as distinct between juvenile-onset and adult-onset disease. MATERIALS AND METHODS: The study used anonymised clinical data on dogs under primary veterinary care at practices enrolled in the UK VetCompass Programme. Case inclusion required recording of a final demodicosis diagnosis for a dermatological condition that was present during the 2013 study period. Risk factor analysis used multivariable logistic regression modelling. RESULTS: In dogs aged <2 years (juvenile-onset), the 1-year period prevalence was 0.48% (95% confidence interval: 0.45 to 0.52). Compared with crossbred dogs, seven breeds showed increased odds of diagnosis with demodex: British bulldog, Staffordshire bull terrier, Chinese shar-pei, dogue de Bordeaux, pug, French bulldog and boxer. Additionally, six breeds showed reduced odds of juvenile demodicosis: Lhasa apso, bichon frise, Labrador retriever, German shepherd dog, shih-tzu and Chihuahua. In dogs aged >4 years (adult-onset), the 1-year period prevalence was 0.05% (95% confidence interval: 0.0.04 to 0.06). Six breeds showed increased odds of demodicosis compared with crossbred dogs: Chinese shar-pei, shih-tzu, West Highland white terrier, pug, boxer and Border terrier. CLINICAL SIGNIFICANCE: Juvenile-onset demodicosis is much more common (about 10 times higher) than the adult-onset form. Knowledge of the predisposed breeds for these two presentations can assist with diagnosis and support the concept of distinct aetiopathogenetic phenotypes.

Correction: Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions.

Correction for 'Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions' by J. A. Perlinger et al., Environ. Sci.: Processes Impacts, 2018, 20, 195-209.

Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions.

Mercury (Hg) emissions pose a global problem that requires global cooperation for a solution. However, neither emissions nor regulations are uniform world-wide, and hence the impacts of regulations are also likely to vary regionally. We report here an approach to model the effectiveness of regulations at different scales (local, regional, global) in reducing Hg deposition and fish Hg concentrations in the Laurentian Great Lakes (GL) region. The potential effects of global change on deposition are also modeled. We focus on one of the most vulnerable communities within the region, an Indigenous tribe in Michigan's Upper Peninsula (UP) with a high fish consumption rate. For the GL region, elements of global change (climate, biomass burning, land use) are projected to have modest impacts (<5% change from the year 2000) on Hg deposition. For this region, our estimate of the effects of elimination of anthropogenic emissions is a 70% decrease in deposition, while our minimal regulation scenario increases emissions by 35%. Existing policies have the potential to reduce deposition by 20% with most of the reduction attributable to U.S. policies. Local policies within the Great Lakes region show little effect, and global policy as embedded in the Minamata Convention is projected to decrease deposition by approximately 2.8%. Even within the GL region, effects of policy are not uniform; areas close to emission sources (Illinois, Indiana, Ohio, Pennsylvania) experience larger decreases in deposition than other areas including Michigan's UP. The UP landscape is highly sensitive to Hg deposition, with nearly 80% of lakes estimated to be impaired. Sensitivity to mercury is caused primarily by the region's abundant wetlands. None of the modeled policy scenarios are projected to reduce fish Hg concentrations to the target that would be safe for the local tribe. Regions like Michigan's UP that are highly sensitive to mercury deposition and that will see little reduction in deposition due to regulations require more aggressive policies to reduce emissions to achieve recovery. We highlight scientific uncertainties that continue to limit our ability to accurately predict fish Hg changes over time.

Clinical and pathological features of hair coat abnormalities in curly coated retrievers from UK and Sweden.

OBJECTIVES: To gain information on hair loss amongst curly coated retrievers by questionnaire and to define the clinical and pathological features of hair coat abnormalities in affected dogs in the United Kingdom and Sweden. MATERIALS AND METHODS: Questionnaires were completed by members of the Curly Coated Retriever Clubs. Fourteen dogs (six in the United Kingdom, eight in Sweden) were clinically examined and skin/hair samples collected for microscopy and histopathology. Blood was collected for haematological, biochemical and endocrine assays. RESULTS: Of 90 dogs surveyed, 39 had current or previous episodes of symmetrical, non-pruritic alopecia and or frizzy coat changes, usually affecting caudal thighs, axillae, dorsum and neck before 18 months of age; 23 dogs had a waxing/waning course. Examined dogs generally matched the pattern described in questionnaires. Hair shaft anomalies comprised occasional distorted anagen bulbs (10 dogs) and transverse fractures (8 dogs). Vertical histopathological sections showed infundibular hyperkeratosis (28 of 30 sections) and low-grade pigment clumping (17 of 30). Subtle telogenisation of hair follicles was unequivocally confirmed by transverse histomorphometric analyses. CLINICAL SIGNIFICANCE: The follicular dysplasia of curly coated retriever reported here is similar to that of Irish water spaniels and Chesapeake Bay retrievers but distinct from that of Portuguese water dogs. The genetic basis requires further assessment.

Hope thinking and past trauma mediate the relationships of body mass index with perceived mental health treatment need and mental health treatment use.

UNLABELLED: Greater body mass is associated with a greater risk of mental health conditions and more frequent mental health treatment use. However, factors that might influence perceived mental health treatment need and mental health treatment use among those of greater weight, including hope thinking, trauma history and perceived mental health treatment stigma, are not well understood. OBJECTIVE: The objective of this study was to determine if hope thinking, trauma history and/or perceived mental health treatment stigma mediate the relationships of body mass index [BMI] with perceived mental health treatment need and mental health treatment use. METHOD: Primary care clinic patients in the Midwest United States (N = 196; BMI range = 18.5 to 47.0, mean = 29.26 ± 6.61, median = 27.90) were recruited to complete a battery of self-report measures that assessed perceived mental health treatment need, mental health treatment use, hope thinking (Trait Hope Scale), trauma history (a single-item traumatic event history screen from the posttraumatic stress disorder module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and perceived mental health treatment stigma (Stigma Scale for Receiving Psychological Help). RESULTS: Reduced hope thinking and a greater incidence of past trauma accounted for greater perceived mental health treatment need and greater mental health treatment use among those of greater BMI. BMI was not related to perceived unmet mental health treatment need. CONCLUSION: Increased perceived mental health treatment need and mental health treatment use among those of greater BMI may be explained by lower hope thinking and a greater incidence of trauma in this population. Heavier patients may benefit from interventions designed to augment hope and address traumatic histories.

Health-related quality of life in neurology.

CONTEXT: In a climate of growing concern about costs of health care, professional accountability, and the effectiveness and efficiency of treatment, neurologists should understand measures of health-related quality of life (HRQoL) and appreciate both their values and their limits. OBJECTIVE: To provide a critical review of current concepts in the measurement of HRQoL, with particular emphasis on those pertaining to neurologic conditions. DESIGN: A selective overview of measurement strategies and specific instruments. SETTING: Clinical and research settings. PARTICIPANTS: Special attention to people with such conditions as multiple sclerosis and Parkinson disease. MAIN OUTCOME MEASURES: The utility and relevance to neurologists of available measures of HRQoL. RESULTS: There are both generic and condition- or disease-specific measures of HRQoL. Though many measures do not elicit response or are even offensive to people with such conditions as multiple sclerosis and Parkinson disease, other measures pertain directly to their circumstances and needs. CONCLUSIONS: Measures of HRQoL are both meaningful and relevant to neurologists. However, they must be refined-enabled-and used in combinations to address the clinical and existential realities of many neurologic conditions. Arch Neurol. 2000;57:1224-1227

There is no regulatory role for induced nitric oxide in the regulation of the in vitro proliferative response of bovine mononuclear cells to mitogens, alloantigens or superantigens.

Nitric oxide (NO) is a potent cellular mediator which has been shown to modulate several immune mechanisms. Between species, however, there are considerable differences regarding the signals required for induction of NO as well as the kind of cells capable of producing NO. The object of this study was to determine the kinetics of NO production of bovine blood mononuclear cells (boMNC) stimulated in vitro and to investigate whether it modulates their proliferative response following allogeneic (mixed leukocyte cultures, aMLC), mitogenic (PWM, Con A) or superantigenic (SEA, SEB) stimulation. NO production was indirectly determined with the Griess reagent measuring nitrite (NO2-). Significant but low amounts of NO could be detected as early as day 3 after in vitro stimulation and did noly slightly increase during the 6-8 day culture period. Superantigens (SEA, SEB) and aMLCs (4.3-5.2 microM NO2-) induced a significantly higher nitrite accumulation compared to Con A (2.6 microM NO2-). Generation of nitrite, most likely produced by monocytes/macrophages, could be inhibited by 1 mM N-monomethyl-L-arginine (NMLA). Flow cytometric characterization of various cellular responses revealed no differences between cultures with or without NMLA. This included the determination of blastogenesis, absolute numbers of viable cells, expression density of activation markers (MHC class II, IL-2R alpha) and cellular subpopulations (CD4+, CD8+, sIg+) among blasts. In addition, exogenously provided NO via SNOG in non-toxic concentrations (10(-5)-10(-4) M) did not alter the proliferative reaction of boMNC in vitro. The results suggest that NO is induced after in vitro stimulation of boMNC, however, at a low level, and without having any positive or suppressive effects on the so far tested cellular parameters of activation and proliferation.

Superantigen-dependent accelerated death of bovine neutrophilic granulocytes in vitro is mediated by blood mononuclear cells.

While classical interactions of bacterial superantigens (SAgs) with antigen presenting cells and T cells have been studied intensively, the potential interactions of SAgs with granulocytes (PMNs) have gained much less attention. We investigated if in the bovine system SAgs have any direct or indirect influence on the fate of granulocytes, which are among those cells primarily responsible for the elimination of superantigen-producing bacteria. The tested SAgs (SEA, SEB) had no apparent direct effect on PMN viability (neutrophils and eosinophils). However, in the presence of blood mononuclear cells (MNCs), SAgs led to an accelerated death of neutrophils but not of eosinophils. Compared to medium controls, in SAg-stimulated cultures only about 20-50% of the neutrophils survived after 24 hours in vitro. Accelerated death of neutrophils required the presence of at least 10% MNC and started between 2.5-24 h after initiation of the co-culture between MNC and PMN. Minimal effective SEA concentrations ranged between 10-100 pg/l (SEB 0.1-10 ng/l). The effect could be mimicked by culture supernatants of SAg-stimulated MNCs, suggesting that direct cell-cell interactions are not required for the killing. In the human system, where we tested the role of TNF-alpha, an antibody specific for this cytokine was not able to abolish the death of human neutrophils. Brefeldin A, an inhibitor of golgi transport and cytokine secretion, which blocked the SAg-induced activation of bovine MNC did not abolish the killing of neutrophils. Blocking of nitric oxide generation or PGE2 synthesis also could not alter the SAg-induced killing of bovine neutrophils. The observed indirect negative effects of SAgs on neutrophils may provide new insights in mechanisms by which superantigens modulate the hosts immune response.

Prostaglandin E2 is variably induced by bacterial superantigens in bovine mononuclear cells and has a regulatory role for the T cell proliferative response.

Signal transduction in antigen presenting cells via MHC class II molecules induces production of prostaglandin E2 (PGE2) known to possess immunoregulatory potential. Since Staphylococcus aureus superantigens (SAgs) utilize MHC class II molecules as primary ligands, we wanted to know whether PGE2 is induced after in vitro SAg stimulation of bovine blood mononuclear cells (boMNC), and whether this arachidonic acid metabolite modulates the preferential SAg-induced proliferative response of bovine CD8+ T cells. SEB as well as SEA induced maximal amounts of PGE2 on day 2 of culture (1-2.5 x 10(-8) mol/l per 2 x 10(5) boMNC). PGE2 production could be inhibited completely by indomethacin (10(-5) mol/l) causing enhanced proliferation of boCD4+ T cells (174%) as well as of boCD8+ T cells (122%) between day 4 and 6 of the in vitro culture, however, only in a subset of the tested animals. Notably, the striking preference of proliferation of boCD8+ over boCD4+ T cells following SAg stimulation remained largely unchanged after inhibition of endogenous PGE2 synthesis or after addition of exogenous PGE2. Higher concentrations of exogenously added PGE2 (> or = 10(-8) mol/l) inhibited the proliferation reaction, mainly due to an increased death rate of both CD4+ and CD8+ blasts. In contrast, lower PGE2 concentrations between 10(-8)-10(-9) mol/l even slightly enhanced the proliferation of both T cell subsets, depending on the individual cell donor. Summing up: These data show that SAgs, indeed, can induce PGE2 production in boMNC which can enhance or reduce the proliferative response of bovine CD4+ and CD8+ T cells.

Choosing a health plan: what information will consumers use?

Employers and policymakers are looking for ways to encourage competition among health plans, thus lowering costs and improving quality. Employers hope to foster competition among health plans by creating standardized measures of quality that supplement the traditional benefits and cost information employees use to compare plans and make choices. This DataWatch examines employees' interest in standardized measures of plan performance. Results from a survey of Massachusetts state employees show that cost and benefit information receive high rankings, but certain plan performance information does not.

How well do Americans understand their health coverage?

Data from two surveys are used in this DataWatch to explore Americans' understanding of their health insurance. First, data from a national survey of consumers are used to examine if people with private health insurance correctly report their coverage for six services. Second, information from an evaluation of a pilot project of subsidized insurance in New York is used to investigate how well newly insured persons understand their coverage. Based on these surveys, almost all privately insured people understand the basic elements of their insurance plans but underestimate their coverage for mental health, substance abuse, and prescription drug benefits and overestimate their coverage for long-term care. People who are newly insured in physician networks or health maintenance organizations seem uncertain about what services their plan covers and restrictions on their choice of hospitals.