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Recent research has shown that sexual and/or gender minority voters are prone to mobilizing when LGBT+ issues are on the political agenda. This increased level of political engagement is attributed to the experience of discrimination, understood both in legal and social terms, which spurs LGBT+ individuals to participate with the aim of advancing their rights. However, a crucial question remains unanswered: do these gaps in participation persist in contexts where core LGBT+ rights are protected? Drawing from comprehensive and verified data on the population of Sweden, this study finds evidence of a positive and sustained sexuality‐driven voter turnout gap across multiple elections. This gap manifests itself both shortly and a decade after the enactment of same‐sex marriage and shows no tangible signs of abating. In addition to improving our knowledge of political participation patterns among sexual minorities, these findings underscore the potential role of minority rights protection as a mechanism to ensure enduring inclusion of social minority groups within democratic processes. [ABSTRACT FROM AUTHOR]

Background: Provoked vestibulodynia (PVD) causes suffering in many women's lives due to its impact on relationships, sexual functioning and functioning in other key domains. Objective: Here, we report a randomized controlled trial conducted to examine whether Acceptance and Commitment Therapy (ACT) with a focus on values‐based exposure, delivered online, benefits women with PVD. Methods: Participants (n = 88) were randomized to either guided online ACT for 10 weeks or a wait‐list control group. Outcomes were assessed at baseline, post treatment and 1 year later. Analyses were based on intention to treat using linear mixed models. Results: There were significant group differences on the primary outcomes, Female Sexual Index and Female Sexual Distress Scale, in favour of online ACT with moderate effect sizes. Differences were also found on several secondary outcomes and therapeutic process measures, all in favour of ACT. No differences were found at post‐treatment for depression or anxiety. At the 1‐year follow‐up, results were maintained and a difference between baseline and follow‐up was also found for depression. Conclusion/Significance: In summary, a relatively brief, guided, online version of ACT appears to produce benefits for women with PVD and related impacts on daily functioning. 50% to 60% of the women who participated in the treatment reliably improved in sexual functioning and distress. [ABSTRACT FROM AUTHOR]

Spending time in forests benefits human well‐being, but the importance of forest characteristics on well‐being is unclear. This knowledge could help guide forest management decisions to improve outcomes for both people and nature.The overall aim of this study was to investigate how psychological restoration, defined as psychological recovery processes in nature, may be supported by forest characteristics. We (1) investigated how perceptions of restoration (perceived restorativeness) were linked to specific forest characteristics. More specifically, we selected attributes included in nature protection legislation in Germany (beauty, diversity and uniqueness) as the basis to evaluate how forest characteristics were related to perceived restorativeness. Additionally, we (2) tested differences in the assessments of these attributes between forestry experts and people from the general public. Based on the results of the first two objectives (1, 2), we (3) predicted how forest management that affects forest characteristics may impact psychological restoration today and in the future.We developed a perceived restorativeness model based on attributes stated in the German Nature Conservation Act and specific forest structure variables. Drawing from the literature, we included perceived naturalness as an additional key predictor for restoration. Forestry experts and participants from the general public were then asked to rate computer‐generated forest stand pictures on these attributes and restorativeness.We found that all attributes were positively associated with perceived restorativeness, but perceived beauty was most important. Perceived uniqueness was statistically significant, but the strength of the relationship was weak. Mixed forests were rated as most beautiful, while coniferous forest stands were rated as least beautiful. The general public gave higher ratings than forestry experts on all attributes, but the pattern was similar. Based on participant ratings, forests left without management (Set‐aside), followed by forests with management aiming for resilience to climate change (Adaptation forestry), both supporting biodiversity conservation, showed the highest perceived restorativeness over the course of 100 years.Based on our results, it could be recommendable to increase forest diversity, especially in areas with many visitors. However, more nuanced knowledge involving diverse stakeholders is needed to inform forest management decisions on landscape level. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Introduction: Brachial plexus birth injury is the most common birth injury causing permanent disability in Finland. This study aimed to assess risk factors of a permanent brachial plexus birth injury and calculate the incidence. Material and methods: This is a retrospective population‐based study including all deliveries between 2006 and 2022 in Southern Finland. The number of children born, obstetric data, and migrant status were gathered from the registries of the Finnish Institute for Health and Welfare, and Statistics Finland. Race of the mothers of children with a permanent brachial plexus birth injury was recorded. The severity of permanent brachial plexus birth injury was assessed using the 3‐month Toronto test score. A lower score was indicative of a more severe injury (scored 0–10). Results: One hundred of the 298 428 children born during the 17‐year study period sustained a permanent brachial plexus birth injury (0.34 per 1000). Mothers of children with a permanent brachial plexus birth injury had a higher body mass index (29 vs. 24 kg/m2) and their pregnancies were more often complicated by diabetes (28% vs. 12%), shoulder dystocia (58% vs. 0.3%), and/or assisted deliveries (45% vs. 10%) compared with all other mothers (p < 0.001). Thirty two of the 52 725 children born to migrant mothers had a permanent brachial plexus birth injury (0.61 per 1000). The incidence of permanent brachial plexus birth injury was 5.7 times higher among children of Black migrants from Africa (18/11 738, 1.53 per 1000) compared with children of native mothers (0.27 per 1000). Black mothers had a higher body mass index at the start of pregnancy (29 vs. 26 kg/m2, p = 0.02) compared with Caucasians. Children of Black mothers had a more severe injury compared with all others (p = 0.007) with a mean 3‐month Toronto test score of 4.2 (range 0.0–6.5, SD ±1.6) vs. 5.6 (range 0.0–9.3, SD ±2.2). Conclusions: Shoulder dystocia and assisted delivery are the most important risk factors for a permanent brachial plexus birth injury. Black race was associated with a higher rate and a more severe permanent brachial plexus birth injury. [ABSTRACT FROM AUTHOR]

Introduction: Yellow fever is caused by an RNA flavivirus. Immunisation in conjunction with vector control is at the forefront of yellow fever control and elimination. Objective: This narrative review describes the impact and importance of yellow fever vaccinations for northern Australian health practitioners. Design: Selected key policies, studies and medical guidelines are reviewed and presented. Finding: Large yellow fever outbreaks, associated with vector spread, have occurred in the last decade in Africa and South America, increasing the risk of international spread of the virus. Mobile populations, like travellers or migrant workers, continue to be at risk of yellow fever. Quality assurance, including yellow fever centre accreditation and initiatives to decrease fraudulent yellow fever vaccination documentation, has evolved in the past few years. Fractional dosing of yellow fever vaccines has been shown to provide protection for 1 year in outbreak scenarios, but further studies are needed. Discussion: Although Australia is yellow fever‐free, the disease could be introduced by viraemic persons as a competent Aedes mosquito vector is present in northern Australia. In addition to surveillance and vector control, health education and yellow fever vaccination remain the best lines of defence. In the event of an outbreak, a response via fractional dosing could prove to be effective in controlling the virus. Conclusion: Health care providers in northern Australia should be aware of the risks of yellow fever and its introduction to northern Australia and be able to discuss vaccination status with their clients when needed. [ABSTRACT FROM AUTHOR]

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH‐SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV‐infected SH‐SY5Y cells showed increased LC3‐I‐LC3‐II conversion as well as co‐localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy‐associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV‐infected cells. In conclusion, these results demonstrate a neuro‐protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease. [ABSTRACT FROM AUTHOR]

Background: Fibrocartilaginous embolic myelopathy (FCE) is a well‐documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined. Objectives: Define the association of the chondrodystrophy‐associated FGF4L2 retrogene with histopathologically confirmed cases of FCE. Animals: Ninety‐eight dogs with a histopathologic diagnosis of FCE. Methods: Retrospective multicenter study. Dogs were genotyped for the FGF4L2 and FGF4L1 retrogenes using DNA extracted from formalin‐fixed, paraffin‐embedded tissue. Associations between breed, FCE and retrogene status were investigated with reference to a hospital population and known breed and general population allele frequencies. Results: FGF4L2 genotype was defined in 89 FCE cases. Fibrocartilaginous embolic myelopathy was present in 22 dogs from FGF4L2‐segregating breeds with allele frequencies of ≥5%; however, all dogs were wild type. Two Labrador retrievers with FCE carried FGF4L2 alleles. Frequency of the FGF4L2 allele was significantly (P <.001) and negatively associated with FCE relative to predicted hospital‐population dogs. FCE was overrepresented in Boxer, Great Dane, Yorkshire Terrier, Bernese Mountain Dog, Miniature Schnauzer, Rottweiler, and Shetland Sheepdog breeds. Conclusions and Clinical Importance: Study data based on genotypically and histopathologically defined cases support the historical observation that FCE is uncommon in chondrodystrophic dog breeds. FGF4 plays an important role in angiogenesis and vascular integrity; anatomical studies comparing chondrodystrophic and non‐chondrodystrophic dogs might provide insight into the pathogenesis of FCE. [ABSTRACT FROM AUTHOR]

Music and language are two fundamental forms of human communication. Many studies examine the development of music‐ and language‐specific knowledge, but few studies compare how listeners know they are listening to music or language. Although we readily differentiate these domains, how we distinguish music and language—and especially speech and song— is not obvious. In two studies, we asked how listeners categorize speech and song. Study 1 used online survey data to illustrate that 4‐ to 17‐year‐olds and adults have verbalizable distinctions for speech and song. At all ages, listeners described speech and song differences based on acoustic features, but compared with older children, 4‐ to 7‐year‐olds more often used volume to describe differences, suggesting that they are still learning to identify the features most useful for differentiating speech from song. Study 2 used a perceptual categorization task to demonstrate that 4–8‐year‐olds and adults readily categorize speech and song, but this ability improves with age especially for identifying song. Despite generally rating song as more speech‐like, 4‐ and 6‐year‐olds rated ambiguous speech–song stimuli as more song‐like than 8‐year‐olds and adults. Four acoustic features predicted song ratings: F0 instability, utterance duration, harmonicity, and spectral flux. However, 4‐ and 6‐year‐olds' song ratings were better predicted by F0 instability than by harmonicity and utterance duration. These studies characterize how children develop conceptual and perceptual understandings of speech and song and suggest that children under age 8 are still learning what features are important for categorizing utterances as speech or song. Research Highlights: Children and adults conceptually and perceptually categorize speech and song from age 4.Listeners use F0 instability, harmonicity, spectral flux, and utterance duration to determine whether vocal stimuli sound like song.Acoustic cue weighting changes with age, becoming adult‐like at age 8 for perceptual categorization and at age 12 for conceptual differentiation.Young children are still learning to categorize speech and song, which leaves open the possibility that music‐ and language‐specific skills are not so domain‐specific. [ABSTRACT FROM AUTHOR]

The phenomenon of populism and its relationship with modern democracy has gained considerable attention in recent years. This article aims at advancing our understanding of how populism affects different models of democracy and tests the proposed arguments empirically. Building on a large scholarly literature on populism and democracy, we take stock of existing arguments and theorize which democratic models may be affected by populism in a positive or negative way. Moreover, we move beyond the normative debate and analyse the effect of populism in power on different models of democracy empirically. We do so by merging data on populist governments in Europe and Latin America from 1995 until today with the Varieties of Democracy dataset, which enables us to capture the relationship between populism and different democratic models in these regions. Despite mixed‐theoretical expectations, our results suggest a rather negative impact of populism on the electoral, liberal and deliberative models of democracy. [ABSTRACT FROM AUTHOR]

Introduction: Von Willebrand disease (VWD) is the most widespread congenital bleeding disorder. Caregivers are highly involved in its treatment, and from the time of the child's bleeding diagnosis, they face new demands such as recognition of bleeds and treatment options. Aim: The aim of this study was to assess Health related quality of life (HRQoL) in caregivers of children with moderate and severe VWD in Sweden, and to describe the impact of psychosocial aspects on the burden. Methods: A multicentre, cross‐sectional study. The Short Form 36 Health Survey (SF‐36) was used to assess HRQoL. Caregiver burden was measured using The HEMOphilia associated Caregiver Burden scale (HEMOCAB). Children´s clinical data were collected from the Swedish national registry for bleeding disorders. Results: Seventy caregivers of children with moderate or severe VWD were included. Caregivers of children with moderate VWD scored significantly lower in the mental health domains on SF‐36, compared to matched normative data. Psychosocial aspects that significantly impacted the caregiver burden negatively measured by HEMOCAB total score were: if the caregiver reported that VWD affected their life in general (p =.001), if the child was absent from preschool/school ≥2 day/12 months due to VWD (p =.002) or that VWD had a financial impact on the family (p =.001). Conclusion: This study contributes to knowledge about caregivers' HRQoL and highlights the situation of caregivers of children with moderate VWD. Furthermore, the caregiver burden was negatively affected by psychosocial aspects. Clinical follow‐ups should include assessment of psychosocial aspects to identify caregivers that are at risk of high burden. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that steady‐state evoked potentials may be a useful measure of beat perception, particularly when obtaining traditional, explicit measures of beat perception is difficult, such as with infants or non‐human animals. Although attending to a stimulus is not necessary for most traditional applications of steady‐state evoked potentials, it is unknown how attention affects steady‐state evoked potentials that arise in response to beat perception. Additionally, most applications of steady‐state evoked potentials to measure beat perception have used repeating rhythms or real music. Therefore, it is unclear how the steady‐state response relates to the robust beat perception that occurs with non‐repeating rhythms. Here, we used electroencephalography to record participants' brain activity as they listened to non‐repeating musical rhythms while either attending to the rhythms or while distracted by a concurrent visual task. Non‐repeating auditory rhythms elicited steady‐state evoked potentials at perceived beat frequencies (perception was validated in a separate sensorimotor synchronization task) that were larger when participants attended to the rhythms compared with when they were distracted by the visual task. Therefore, although steady‐state evoked potentials appear to index beat perception to non‐repeating musical rhythms, this technique may be limited to when participants are known to be attending to the stimulus. [ABSTRACT FROM AUTHOR]

Objective: To study the impact of shoulder dystocia (SD) simulation training on the management of SD and the incidence of permanent brachial plexus birth injury (BPBI). Design: Retrospective observational study. Setting: Helsinki University Women's Hospital, Finland. Sample Deliveries with SD. Methods: Multi‐professional, regular and systematic simulation training for obstetric emergencies began in 2015, and SD was one of the main themes. A study was conducted to assess changes in SD management and the incidence of permanent BPBI. The study period was from 2010 to 2019; years 2010–2014 were considered the pre‐training period and years 2015–2019 were considered the post‐training period. Main outcome measures: The primary outcome measure was the incidence of permanent BPBI after the implementation of systematic simulation training. Changes in the management of SD were also analysed. Results: During the study period, 113 085 vertex deliveries were recorded. The incidence of major SD risk factors (gestational diabetes, induction of labour, vacuum extraction) increased and was significantly higher for each of these factors during the post‐training period (p < 0.001). The incidence of SD also increased significantly (0.01% vs 0.3%, p < 0.001) during the study period, but the number of children with permanent BPBI decreased by 55% after the implementation of systematic simulation training (0.05% vs 0.02%, p < 0.001). The most significant change in the management of SD was the increased incidence of successful delivery of the posterior arm. Conclusions: Systematic simulation‐based training of midwives and doctors can translate into improved individual and team performance and can significantly reduce the incidence of permanent BPBI. [ABSTRACT FROM AUTHOR]

The current distribution and population structure of many species were, to a large extent, shaped by cycles of isolation in glacial refugia and subsequent population expansions. Isolation in and postglacial expansion through heterogeneous environments led to either neutral or adaptive divergence. Norway spruce is no exception, and its current distribution is the consequence of a constant interplay between evolutionary and demographic processes. We investigated population differentiation and adaptation of Norway spruce for juvenile growth, diameter of the stem, wood density, and tracheid traits at breast height. Data from 4461 phenotyped and genotyped Norway spruce from 396 half‐sib families in two progeny tests were used to test for divergent selection in the framework of QST vs. FST. We show that the macroscopic resultant trait (stem diameter), unlike its microscopic components (tracheid dimensions) and juvenile growth, was under divergent selection that predated the Last Glacial Maximum. Altogether, the current variation in these phenotypic traits in Norway spruce is better explained by local adaptation to ancestral environments than to current ones, where populations were partly preadapted, mainly through growth‐related traits. [ABSTRACT FROM AUTHOR]

Although parents of children with bleeds and prophylactic treatment had significantly higher burdens, no significant differences in parental burden (HEMOCAB total score) were seen between the three types of VWD. In non-responder parents (n = 35) the children had a median age of 9 years; 14.3% had type 1 VWD, 71.5% had type 2 VWD, 5.7% had type 3 VWD and 8.6% had an unknown type of VWD. For example, if the child was diagnosed with hereditary reasons, the parents will have been familiar with VWD disease and treatment, and the child might have a milder bleeding phenotype - the vast majority of children diagnosed due to hereditary reasons had type 1 or 2 VWD. Von Willebrand disease (VWD) impacts on the health-related quality of life (HR-QoL) of children and adults, the HR-QoL being strongly associated with bleeding phenotype.[[1], [3]] Managing daily family life with a chronically ill child means that, to some extent, the parents need to be an active part of the treatment.[4] One consequence of a child's illness is personal suffering for the parent. [Extracted from the article]

Aim: The aim of this work was to investigate whether nonsteroidal anti‐inflammatory drugs (NSAIDs) could be beneficial or harmful when used perioperatively for colorectal cancer patients, as inflammation may affect occult disease and anastomotic healing. Method: This is a protocol‐based retrospective cohort study on colorectal cancer patients operated on between 2007 and 2012 at 21 hospitals in Sweden. NSAID exposure was retrieved from postoperative analgesia protocols, while outcomes and patient data were retrieved from the Swedish Colorectal Cancer Registry. Older or severely comorbid patients, as well as those with disseminated or nonradically operated tumours were excluded. Multivariable regression with adjustment for confounders was performed, estimating hazard ratios (HRs) for long‐term outcomes and odds ratios (ORs) for short‐term outcomes, including 95% confidence intervals (CIs). Results: Some 6945 patients remained after exclusion, of whom 3996 were treated at hospitals where a NSAID protocol was in place. No association was seen between NSAIDs and recurrence‐free survival (HR 0.97, 95% CI 0.87–1.09). However, a reduction in cancer recurrence was detected (HR 0.83, 95% CI 0.72–0.95), which remained significant when stratifying into locoregional (HR 0.68, 95% CI 0.48–0.97) and distant recurrences (HR 0.85, 95% CI 0.74–0.98). Anastomotic leakage was less frequent (HR 0.69%, 95% CI 0.51–0.94) in the NSAID‐exposed, mainly due to a risk reduction in colo‐rectal and ileo‐rectal anastomoses (HR 0.47, 95% CI 0.33–0.68). Conclusion: There was no association between NSAID exposure and recurrence‐free survival, but an association with reduced cancer recurrence and the rate of anastomotic leakage was detected, which may depend on tumour site and anastomotic location. [ABSTRACT FROM AUTHOR]

Objectives: To investigate gene alterations as diagnostic and prognostic markers in upper tract urothelial carcinoma (UTUC). Patients and Methods: Patients with UTUC who underwent nephroureterectomy between 2005 and 2012 were followed until November 2020. DNA was extracted from paraffin‐embedded tumour tissue. Next‐generation sequencing using a 388‐gene panel was performed. First a blinded analysis using principal component analysis and hierarchical clustering was used to search for patterns of mutations. Then a comparative analysis using analysis of variance (ANOVA) was used to search for mutations enriched in groups of various grades, stages, and survival. In addition, careful manual annotation was used to identify pathogenic mutations over‐represented in tumours of high grade/stage and/or poor survival. Results: A total of 39 patients were included. All tumour stages and grades were represented in the cohort. The median follow‐up was 10.6 years. In all, 11 patients died from UTUC during the follow‐up. Tumour mutational burden showed a statistically significant correlation with stage, grade, and stage + grade. Grade 1, Grade 2, and Grade 3 tumours had different mutational patterns. Patients who died from UTUC had pathogenic mutations in specific genes e.g. tumour protein p53 (TP53) and HRas proto‐oncogene, GTPase (HRAS). Patients with Ta Grade 1 tumours with a known pathogenic fibroblast growth factor receptor 3 (FGFR3) mutation did not die from UTUC. Conclusion: The genetic analysis was highly concordant with histopathological features and added prognostic information in some cases. Thus, results from genomic profiling may contribute to the choice of treatment and follow‐up regimens in the future. [ABSTRACT FROM AUTHOR]

We determined that the Tp53 stain is wild-type and the Smad4 stain is intact in both regions. gl Our identification of a microscopic, intraparenchymal pancreatic cancer metastasis highlights one mechanism for tumour recurrence in the remnant pancreas after apparently curative surgery. Using CODA, a technique for three-dimensional reconstruction of large tissues, Kiemen et al. report observation of a microscopic focus of pancreatic cancer found in the vasculature of grossly normal human pancreas tissue resected adjacent to a large tumour. Gain of tumour protein I Tp53 i is found in approximately 85% of pancreatic cancers, while loss of I Smad4 i is found in approximately 55% of pancreatic cancers.[5] We found that both foci had wild-type labelling for I Tp53 i and intact I Smad4 i expression (Figure 2). [Extracted from the article]

Aims: Despite signals from clinical trials and mechanistic studies implying different resilience to heart failure (HF) depending on gender, the impact of gender on presentation and outcomes in patients with HF remains unclear. This study assessed the impact of gender on clinical presentation and outcomes in patients with HF referred to a specialised tertiary HF service. Methods and results: Consecutive patients with HF referred to a specialised tertiary HF service offering advanced therapy options including left ventricular assist devices (LVAD) and heart transplantation were prospectively enrolled from August 2015 until March 2018. We assessed clinical characteristics at baseline and performed survival analyses and age‐adjusted Cox regression analyses in men vs. women for all‐cause death and a combined disease‐related endpoint comprising death, heart transplantation, and LVAD implantation. Analyses were performed for the overall study population and for patients with HF with reduced ejection fraction (HFrEF). Of 356 patients included, 283 (79.5%) were male. The median age was 58 years (interquartile range 50–67). Two hundred and fifty‐one (74.5%) patients had HFrEF. HF aetiology, ejection fraction, functional status measures, and most of the cardiac and non‐cardiac comorbidities did not differ between men and women. In a median follow‐up of 3.2 years, 50 patients died (45 men, 5 women), 15 patients underwent LVAD implantation, and 8 patients heart transplantation. While all‐cause death was not significantly different between both genders in the overall population [16.9 vs. 6.0%, P = 0.065, hazard ratio (HR) 2.29 (95% confidence interval 0.91–5.78), P = 0.078], in the HFrEF subgroup, a significant difference between men and women was observed [20.7% vs. 3.9%, P = 0.017, HR 3.67 (95% confidence interval 1.13–11.91), P = 0.031]. The combined endpoint was more often reached in men than in women in both the overall population [21.6% vs. 9.0%, P = 0.053, HR 2.51 (1.08–5.82), P = 0.032] and the HFrEF subgroup [27.1% vs. 7.7%, P = 0.015, HR 3.58 (1.29–9.94), P = 0.014]. Conclusions: Patients referred to a specialised tertiary HF service showed a similar clinical profile without relevant gender differences. In the mid‐term follow‐up, more male than female patients died or underwent heart transplantation and LVAD implantation. These findings call for independent validation and for further research into gender‐specific drivers of HF progression. [ABSTRACT FROM AUTHOR]

Aims: Mechanical circulatory support devices (MCS) are potentially effective treatments for cardiogenic shock (CS) and are thus evaluated in several randomised controlled trials (RCTs). However, it is not clear how enrolment criteria of these RCTs apply to a real‐world CS population. This study aimed to shed light on eligibility to these trials. Methods and results: Pragmatic enrolment criteria for the IABP‐SHOCK II, the DanGer‐SHOCK, the ECLS‐SHOCK and the EURO‐SHOCK trials were retrospectively applied to 1305 CS patients admitted to a tertiary care hospital between 2009 and 2019. Based on this, major enrolment criteria were identified and outcome between eligible and ineligible patients was assessed. In this study, 415 (31.8%) patients were eligible for any study. Lowest eligibility was observed for DanGer‐SHOCK (11.9%) and the highest for IABP‐SHOCK II (26.9%). Over all trials, inclusion criteria were more restrictive than exclusion criteria and absence of CS caused by acute myocardial infarction (AMI) was the primary reason for non‐eligibility. However, even in CS caused by AMI, enrolment criteria were only met in 65.4% of patients. Importantly, 30‐day mortality was high across all patients/trials, irrespective of eligibility or non‐eligibility. Conclusion: The present study highlights that current and past RCTs only reflect about a third of the overall CS population. While enrolment criteria are a necessary aspect of RCTs, their application limits generalisability of the trials' findings. More trials on CS sub‐populations not represented by current or past trials, e.g. CS not caused by AMI, are needed, especially as mortality is high irrespective of eligibility status. [ABSTRACT FROM AUTHOR]

Summary: The domestic cat (Felis silvestris catus) is a valued companion animal throughout the world. Over 60 different cat breeds are accepted for competition by the cat fancy registries in different countries. Genetic markers, including short tandem repeats and SNPs, are available to evaluate and manage levels of inbreeding and genetic diversity, population and breed structure relationships, and individual identification for forensic and registration purposes. The International Society of Animal Genetics (ISAG) hosts the Applied Genetics in Companion Animals Workshop, which supports the standardization of genetic marker panels and genotyping for the identification of cats via comparison testing. SNP panels have been in development for many species, including the domestic cat. An ISAG approved core panel of SNPs for use in cat identification and parentage analyses is presented. SNPs (n = 121) were evaluated by different university‐based and commercial laboratories using 20 DNA samples as part of the ISAG comparison testing procedures. Different SNP genotyping technologies were examined, including DNA arrays, genotyping‐by‐sequencing and mass spectroscopy, to select a robust and efficient panel of 101 SNPs as the ISAG core panel for cats. The SNPs are distributed across all chromosomes including two on the X chromosome and an XY pseudo‐autosomal sexing marker (zinc‐finger XY; ZFXY). A population study demonstrated that the markers have an average polymorphic information content of 0.354 and a power of exclusion greater than 0.9999. The SNP panel should keep testing affordable while also allowing for the development of additional panels to monitor health, phenotypic traits, hybrid cats and highly inbred cats. [ABSTRACT FROM AUTHOR]

Background: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disorder associated with a vitamin E deficiency within the first year of life. Vitamin E consists of 8 isoforms metabolized by the CYP4F2 enzyme. No antemortem diagnostic test currently exists for eNAD/EDM. Hypothesis/Objectives: Based on the association of α‐tocopherol deficiency with the development of eNAD/EDM, we hypothesized that the rate of α‐tocopherol, but not γ‐tocopherol or tocotrienol metabolism, would be increased in eNAD/EDM‐affected horses. Animals: Vitamin E metabolism: Proof of concept (POC) study; eNAD/EDM‐affected (n = 5) and control (n = 6) horses. Validation study: eNAD/EDM‐affected Quarter Horses (QHs; n = 6), cervical vertebral compressive myelopathy affected (n = 6) horses and control (n = 29) horses. CYP4F2 expression and copy number: eNAD/EDM‐affected (n = 12) and age‐ and sex‐matched control (n = 11‐12) horses. Methods: The rates of α‐tocopherol/tocotrienol and γ‐tocopherol/tocotrienol metabolism were assessed in equine serum (POC and validation) and urine (POC only) using liquid chromatography tandem mass spectrometry (LC‐MS/MS). Quantitative reverse‐transcriptase PCR (qRT‐PCR) and droplet digital (dd)‐PCR were used to assay expression and genomic copy number of a CYP4F2 equine ortholog. Results: Metabolic rate of α‐tocopherol was increased in eNAD/EDM horses (POC,P <.0001; validation, P =.03), with no difference in the metabolic rate of γ‐tocopherol. Horses with eNAD/EDM had increased expression of the CYP4F2 equine orthologue (P =.02) but no differences in copy number. Conclusions and Clinical Importance: Increased α‐tocopherol metabolism in eNAD/EDM‐affected QHs provides novel insight into alterations in vitamin E processing in eNAD/EDM and highlights the need for high‐dose supplementation to prevent the clinical phenotype in genetically susceptible horses. [ABSTRACT FROM AUTHOR]

Workplace‐collected blood spots deposited on filter paper were analysed with multiplexed affinity‐based protein assays and found to be suitable for proteomics analysis. The protein extension assay (PEA) was used to characterize 92 proteins using 1.2 mm punches in repeated samples collected from 20 workers. Overall, 97.8% of the samples and 91.3% of the analysed proteins passed quality control. Both within and between spot correlations using six replicates from the same individual were above 0.99, suggesting that comparable levels are obtained from multiple punches from the same spot and from consecutive spots. Protein levels from dried blood and wet serum from the same individuals were compared and the majority of the analysed proteins were found to be significantly correlated. These results open up for simplified sample collection of blood in field conditions for proteomic analysis, but also highlight that not all proteins can be robustly measured from dried whole blood. [ABSTRACT FROM AUTHOR]

Objectives: (i) To evaluate immunohistochemical labeling of pre‐iridal monocellular and fibrovascular membranes and (ii) describe the light and scanning electron microscopic (SEM) characteristics of these membranes in glaucomatous and normal/control canine globes. Materials and methods: All globes were evaluated with light microscopy. Immunohistochemical labeling for CD18, Smooth muscle actin (SMA), and CD117 was completed on 40 canine globes with congenital/anterior segment dysgenesis‐associated glaucoma (n = 10), primary/goniodysgenesis‐associated glaucoma (n = 10), secondary glaucoma (n = 10), and normal/control globes (n = 10). SEM was completed on 10 globes: 5 with monocellular membranes, 3 with fibrovascular membranes, and 2 without a histologically detectable membrane. Results: Monocellular membranes were detected in all normal/control globes with light microscopy and appeared to be morphologically very similar to those in diseased globes. CD18 labeling was detected in 9/10 monocellular membranes in normal/control globes, 15/23 monocellular, and 7/8 fibrovascular membranes in globes with glaucoma. SMA and CD117 labeling was not detected in monocellular membranes of normal/control globes. SMA was expressed in 10/23 monocellular and 7/8 fibrovascular membranes of glaucomatous globes. CD117 was expressed in 7/23 monocellular and 5/8 fibrovascular membranes of glaucomatous globes. SEM of monocellular membranes revealed a continuous sheet of mostly spindle cells and few individual round cells that extended over the anterior iris face in normal/control and all glaucomatous globes. Conclusion: Pre‐iridal monocellular membranes are a normal component of the anterior iris surface, and CD18 immunoreactivity suggests some cells within these are of leukocytic origin. SMA and CD117 labeling of monocellular membranes in glaucomatous, but not normal/control globes, suggest metaplastic cellular change secondary to intraocular pathology related to glaucoma. [ABSTRACT FROM AUTHOR]

Background: The only known genetic cause of congenital stationary night blindness (CSNB) in horses is a 1378 bp insertion in TRPM1. However, an affected Tennessee Walking Horse was found to have no copies of this variant. Objectives: To identify the genetic cause for CSNB in an affected Tennessee Walking Horse. Study design: Case report detailing a whole‐genome sequencing (WGS) approach to identify a causal variant. Methods: A complete ophthalmic exam, including an electroretinogram (ERG), was performed on suspected CSNB‐affected horse. WGS data were generated from the case and compared with data from seven other breeds (n = 29). One hundred candidate genes were evaluated for coding variants homozygous in the case and absent in all other horses. Protein modelling was used to assess the functional effects of the identified variant. A random cohort of 90 unrelated Tennessee Walking Horses and 273 horses from additional breeds were screened to estimate allele frequency of the GRM6 variant. Results: ERG results were consistent with CSNB. WGS analysis identified a missense mutation in metabotropic glutamate receptor 6 (GRM6) (c.533C>T p.Thr178Met). This single nucleotide polymorphism (SNP) is predicted to be deleterious and protein modelling supports impaired binding of the neurotransmitter glutamate. This variant was not detected in 273 horses from three additional breeds. The estimated allele frequency in Tennessee Walking Horses is 10%. Main limitations: Limited phenotype information for controls and no additional cases with which to replicate this finding. Conclusions: We identified a likely causal recessive missense variant in GRM6. Based on protein modelling, this variant alters GRM6 binding, and thus signalling from the retinal rod cell to the ON‐bipolar cell, impairing vision in low light conditions. Given the 10% population allele frequency, it is likely that additional affected horses exist in this breed and further work is needed to identify and examine these animals. [ABSTRACT FROM AUTHOR]

Objective: In the present study, we describe the features and functional properties of a new powder cosmetic ingredient, an amorphous mesoporous magnesium carbonate (MMC, also named Upsalite®) with regard to physical characteristics as well as functional attributes. Methods: Physical and functional characterization of MMC, as compared to other common powder cosmetic ingredients (silica, mica, kaolin, talc and starch), was assessed using nitrogen gas adsorption, powder X‐ray diffraction, particle size distribution by laser diffraction, scanning electron microscopy (SEM), and oil and moisture uptake tests. The powder ingredients were also applied on human skin and analysed for short‐ and long‐term mattifying effect, and a new method was developed to measure flashback effect. MMC was tested for skin irritation using an in vitro cell model as well as in vivo, through the Human Repeated Insult Patch Test on 50 human volunteers. Results: Mesoporous magnesium carbonate has a high surface area and pore volume. It has an excellent absorption capacity and can take up both oil and water simultaneously. It provides instant and long‐lasting mattifying effect when applied on human skin without drying or irritating skin and exhibits no measured flashback effect. Conclusion: Mesoporous magnesium carbonate has good sensory and visual characteristics as well as excellent absorbing and mattifying properties, suggesting that it has great potential to replace other powder ingredients currently used as fillers and absorbers in powder cosmetics. [ABSTRACT FROM AUTHOR]

This paper develops a model showing how the environmental liability regime and the precision of the disclosed environmental performance indicator affect managers' incentives (1) to reduce actual pollution and (2) to manipulate the reported pollution. I assume a company with a separation of ownership and control which can be held liable for environmental damages and distinguish between a negligence regime and strict liability. The results suggest that if there is no manipulation but only a lack of precision of the disclosed environmental performance indicator, a negligence rule induces lower actual pollution levels than strict liability even though a negligence rule is considered to be more lenient. If managers are able to manipulate the disclosed environmental performance indicator, they will do so and actual pollution levels will generally increase. While manipulation makes it easier for shareholders to escape liability under a negligence regime, shareholders suffer from manipulation under strict liability due to higher actual pollution and higher expected damage compensation payments. Therefore, the manipulation level is higher under a negligence regime. My analysis contributes to the environmental performance and disclosure literature by showing that the liability regime is an important determinant affecting environmental reporting and actual pollution decisions. [ABSTRACT FROM AUTHOR]

Purpose: To compare the scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and fluorescein angiography (FA) findings in retrievers with a single unilateral circular retinal plaque to those of an English springer spaniel with bilateral retinal dysplasia. Procedures: A retrospective record review identified three dogs with circular retinal plaques that underwent SLO and OCT; in two of the three dogs, FA was also completed. Morphologic changes, lesion measurements, and angiogram characteristics were documented. An English springer spaniel with bilateral retinal dysplasia that had undergone SLO, OCT, and FA was used for comparison. Results: Scanning laser ophthalmoscopy of the retriever dogs revealed circular retinal plaques with a dark periphery located in the tapetal retina. OCT revealed a thickening of the nerve fiber layer corresponding to the circular pattern observed on SLO. Within the circular plaque, the retina was predominantly of normal architecture. FA revealed variable hypofluorescence of both the rim and the center of the circular lesion throughout the early angiogram phases. In the late recirculation phase, small multifocal areas of hyperfluorescence were observed. OCT of geographic retinal dysplasia in the English springer spaniel revealed disorganization of both inner and outer retinal layers, and retinal detachment. Conclusions: Circular plaques observed in the tapetal retina are predominantly formed by a thickening of inner retina, while retinal dysplasia has disorganization of both inner and outer retinal layers. Further etiologic research is needed, including pedigree mapping to determine whether retinal plaques are an acquired or inherited condition. [ABSTRACT FROM AUTHOR]

Summary: Norway spruce is a boreal forest tree species of significant ecological and economic importance. Hence there is a strong imperative to dissect the genetics underlying important wood quality traits in the species. We performed a functional genome‐wide association study (GWAS) of 17 wood traits in Norway spruce using 178 101 single nucleotide polymorphisms (SNPs) generated from exome genotyping of 517 mother trees. The wood traits were defined using functional modelling of wood properties across annual growth rings. We applied a Least Absolute Shrinkage and Selection Operator (LASSO‐based) association mapping method using a functional multilocus mapping approach that utilizes latent traits, with a stability selection probability method as the hypothesis testing approach to determine a significant quantitative trait locus. The analysis provided 52 significant SNPs from 39 candidate genes, including genes previously implicated in wood formation and tree growth in spruce and other species. Our study represents a multilocus GWAS for complex wood traits in Norway spruce. The results advance our understanding of the genetics influencing wood traits and identifies candidate genes for future functional studies. Significance Statement: Wood provides both structural support and a transport route for water and solutes in trees. Our work provides a framework to dissect the genetic nature of wood formation and adds to our understanding of tree growth and development. With the current research focus on wood cell wall biosynthesis in general, and lignocellulose feedstock for biorefineries, we believe that this contribution will be of wide interest for the plant science community. [ABSTRACT FROM AUTHOR]

Purpose: To describe the optical coherence tomography (OCT) and fluorescein angiography changes in dogs with sudden acquired retinal degeneration syndrome (SARDS). Methods: Retinal OCT was performed on 10 SARDS dogs and eight control dogs. Tomograms were collected in four quadrants around the optic nerve. Measurements were collected from the photoreceptor layer, the outer nuclear layer, the outer retina, the inner retina and the whole retina thickness in all quadrants. Sodium fluorescein was injected intravenously and serial fundic photographs were collected for a 5 minute period post‐injection. Results: In all quadrants, the outer nuclear layer (dorsal temporal P = 0.0000, dorsal nasal P = 0.0001, ventral temporal P = 0.0002, ventral nasal P = 0.000) and outer retina (dorsal temporal P = 0.0001, dorsal nasal P = 0.0002, ventral temporal P = 0.0054, ventral nasal P = 0.0084) measurements were significantly decreased in SARDS dogs. The whole retina thickness was significantly decreased in the dorsal temporal (P = 0.0082) and ventral temporal (P = 0.0428) retina. There were no significant differences in the photoreceptor layer thickness or inner retinal thickness between SARDS and control dogs. All SARDS dogs had a loss of definition of all of the photoreceptor bands on OCT. Two SARDS dogs had multifocal small retinal detachments and one of these dogs exhibited fluorescein leaking at the detachment sites. Conclusions: The significant reduction in the outer nuclear layer and the loss of band signals in the photoreceptor layers in dogs with SARDS identified on OCT support the previous histopathology findings. Small detachments may occasionally be detected on OCT and they may leak fluorescein. [ABSTRACT FROM AUTHOR]

This study investigates the environmental performance of 2‐ethylhexanol (2‐EH), as a potential drop‐in transport fuel alternative. Three different biomass‐based production pathways are evaluated and compared using life cycle assessment (LCA) methodology. The environmental impact of 2‐EH is assessed in terms of cumulative energy demand (CED) and global warming potential (GWP). Among the three alternative pathways, 2‐EH produced via syngas results in the lowest primary energy demand and GHG emissions under the baseline assumptions of this work. The two biochemical production pathways (via ethanol and butanol) exhibit higher CED and GWP during biomass conversion steps mainly due to process materials and chemicals used. Process specifications such as transport distance to production facility or the fate of the obtained by‐products are shown to influence the overall environmental impact of the fuel for all studied pathways. The use phase performance of 2‐EH was also considered in this work, as part of a 100% renewable blend and was compared to existing fossil and renewable fuels. The studied blend has the potential to reduce GHG emissions by more than 85% compared to fossil diesel while when certain production pathways are followed, it exhibits lower GWP than renewable fuels already in the market such as ethanol blends and biodiesel. 2‐EH can therefore provide a competitive alternative to fossil transport fuels increasing the share of renewable content in the current vehicle fleet, thus enhancing the efforts for a sustainable transport sector. [ABSTRACT FROM AUTHOR]

Summary: A novel coloration named 'mocha' has been identified in the Burmese cat breed from Thailand. Tyrosinase (TYR) mutations are known to be associated with coat coloration in cats, such as the sable Burmese, the points of the Siamese and albino cats. Additionally, sable Burmese that produced mocha‐colored cats had unexpected genotypes for TYR. Therefore, TYR was considered a candidate gene for mocha in cats. Sanger sequencing for genomic DNA revealed NC_018732.3:chromosome D1:45 898 609_45 898 771dup in exon 2 and intron 2 of TYR. Transcription analysis using cDNA detected c.820_936delinsAATCTC (p.I274_L312delinsNL), which caused a 111‐bp (37 amino acid) deletion in the reading frame of TYR. The identified variant was concordant with the phenotype and segregated with TYR variants in a pedigree of 12 Burmese cats. This findings of this study suggest that TYR is associated with the mocha coloration in cats. The new color variant adds to the allelic series for TYR (C > cb = cs > c, c2) and is recessive to full color (C); however, interactions with the cb and cs alleles are unclear due to the temperature‐sensitivity of the alleles. [ABSTRACT FROM AUTHOR]

Objective: In vitro, in vivo, and open‐label studies suggest that interferon gamma (IFN‐γ 1b) may improve clinical features in Friedreich Ataxia through an increase in frataxin levels. The present study evaluates the efficacy and safety of IFN‐γ 1b in the treatment of Friedreich Ataxia through a double‐blind, multicenter, placebo‐controlled trial. Methods: Ninety‐two subjects with FRDA between 10 and 25 years of age were enrolled. Subjects received either IFN‐γ 1b or placebo for 6 months. The primary outcome measure was the modified Friedreich Ataxia Rating Scale (mFARS). Results: No difference was noted between the groups after 6 months of treatment in the mFARS or secondary outcome measures. No change was noted in buccal cell or whole blood frataxin levels. However, during an open‐label extension period, subjects had a more stable course than expected based on natural history data. Conclusions: This study provides no direct evidence for a beneficial effect of IFN‐γ1b in FRDA. The modest stabilization compared to natural history data leaves open the possibility that longer studies may demonstrate benefit. [ABSTRACT FROM AUTHOR]

A 11‐year‐old neutered male Labrador retriever‐cross dog was presented to the University of Missouri‐Columbia Veterinary Ophthalmology Service for subtle visual deficits. Indirect ophthalmoscopy revealed a smooth, bullous elevation in the superior‐temporal retina OU. Optical coherence tomography (OCT) performed OU showed inner retinal separation consistent with retinoschisis. Electroretinography (ERG) revealed markedly reduced b‐wave amplitudes in the more severely affected eye (OD) compared with the less severely affected eye (OS). The most notable reductions were in the rod response and 30‐Hz flicker b‐waves OD which were approximately 50% of the corresponding amplitudes OS. Implicit times, particularly the a‐wave implicit times, were noticeably longer OD compared with OS. Lesions remained unchanged over 4 months at which time the dog was humanely euthanized for reasons unrelated to the ocular disease. Significant light microscopic ocular findings were bilateral superior temporal peripheral retinoschisis. The separation of the retinal tissue was similar between eyes and effectively divided the outer plexiform layer. In addition, thinning of the surrounding retinal layers was present. To the authors' knowledge, this is the first case of canine retinoschisis diagnosed with OCT, evaluated with electroretinography, and confirmed with light microscopic examination. History, clinical, and diagnostic findings, with the absence of disease progression over time, are analogous with cases of acquired senile retinoschisis in humans. [ABSTRACT FROM AUTHOR]

Atmospheric dispersion modelling is always encumbered by errors and uncertainties originating from different aspects of the weather description as well as the source and dispersion models. Even so, the typical results from these kinds of studies are limited to one realization with no measure of uncertainties in either the temporal or spatial dimensions. This result is then to be interpreted as the most probable outcome given the current information. However, in many situations this limited result and the presentation thereof are far from satisfying and in the worst case even dangerously misleading. To address this shortcoming, this work presents a well‐established method for uncertainty investigation in simulations called Latin hypercube sampling in combination with a weather ensemble which results in an alternative way of estimating the resulting risk area as a function of weather forecast time from a statistical perspective. The main idea with this approach is to use the entire probability distribution of the simulation parameters instead of only one value as is the case in traditional methodology. This is a useful concept that provides additional and valuable information for decision makers. By applying weather ensembles a probabilistic field of risk area, following the atmospheric release of a hazardous substance, can be obtained, in contrast to a traditional deterministic field. This figure illustrates the profound difference that may occur when the risk area is estimated a few days in advance. A methodology to address this issue in combination with other sources of uncertainties is proposed and discussed. [ABSTRACT FROM AUTHOR]

Abstract: A novel case of a canine odontogenic parakeratinized cyst (COPC) that resulted in exophthalmos and palatine, maxillary, and zygomatic bone erosion in a 5‐year‐old Chihuahua dog is reported. Final diagnosis was aided by cross‐sectional imaging (magnetic resonance imaging and computed tomography) and confirmed with histologic examination of the cyst wall. [ABSTRACT FROM AUTHOR]

Summary: Xylan is one of the main compounds determining wood properties in hardwood species. The xylan backbone is thought to be synthesized by a synthase complex comprising two members of the GT43 family. We downregulated all GT43 genes in hybrid aspen (Populus tremula × tremuloides) to understand their involvement in xylan biosynthesis. All three clades of the GT43 family were targeted for downregulation using RNA interference individually or in different combinations, either constitutively or specifically in developing wood. Simultaneous downregulation in developing wood of the B (IRX9) and C (IRX14) clades resulted in reduced xylan Xyl content relative to reducing end sequence, supporting their role in xylan backbone biosynthesis. This was accompanied by a higher lignocellulose saccharification efficiency. Unexpectedly, GT43 suppression in developing wood led to an overall growth stimulation, xylem cell wall thinning and a shift in cellulose orientation. Transcriptome profiling of these transgenic lines indicated that cell cycling was stimulated and secondary wall biosynthesis was repressed. We suggest that the reduced xylan elongation is sensed by the cell wall integrity surveying mechanism in developing wood. Our results show that wood‐specific suppression of xylan‐biosynthetic GT43 genes activates signaling responses, leading to increased growth and improved lignocellulose saccharification. [ABSTRACT FROM AUTHOR]

Abstract: Spinal cord injury (SCI) is a devastating disorder that affects humans and dogs. The prognosis of SCI depends on the severity of the injury and can include varying levels of motor and sensory deficits including devastating paraplegia and quadriplegia. Placental mesenchymal stromal cells (PMSCs) have been shown to improve wound healing and possess neuroprotective and immunomodulatory capabilities, but have not yet been clinically tested for the treatment of SCI. This study established a protocol to isolate fetal PMSCs from canine placentas and characterized their paracrine secretion profile and ability to stimulate neurons in vitro to assess their potential as a treatment option for neurological disorders in dogs. Canine PMSCs (cPMSCs) were plastic adherent and capable of trilineage differentiation. cPMSCs expressed typical MSC markers and did not express hematopoietic or endothelial cell markers. Genotyping of cPMSCs revealed fetal rather than maternal origin of the cells. cPMSCs were viable and mitotically expansive in a collagen hydrogel delivery vehicle, and they secreted the immunomodulatory and neurotrophic paracrine factors interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein 1 (MCP‐1), and vascular endothelial growth factor (VEGF). cPMSCs also stimulated the growth of complex neural networks when co‐cultured with SH‐SY5Y cells, a neuroblastoma cell line used to model neuron growth in vitro. cPMSCs are analogous to human PMSCs. They meet the criteria to be defined as MSCs and represent a potential regenerative therapy option for neurological disorders in dogs with their robust growth in collagen hydrogel, stimulation of neural network formation, and secretion of potent paracrine factors. © 2017 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

A 15-year-old, neutered male, Shih Tzu cross developed progressive corneal stromal thickening and vascularization of the right eye, and 5 months later, of the left eye. Both eyes became blind due to extensive corneal opacification and were enucleated. Light microscopic examination revealed a diffuse corneal infiltrate of neoplastic mesenchymal cells, and immunohistochemistry revealed diffuse cytoplasmic vimentin immunoreactivity and variable cytoplasmic and nuclear immunoreactivity for S100 in the neoplastic cells. Transmission electron microscopy revealed desmosomes between contiguous cells, thread-like cytoplasmic processes coated with basement membrane, extracellular bundles of collagen, and axonal degeneration consistent with features of a nerve sheath neoplasm. This is the first report of primary, bilateral corneal nerve sheath sarcoma in a canine. [ABSTRACT FROM AUTHOR]

Objective The objective of this study is to investigate the structural and functional ocular changes that develop in turkeys exposed to a photoperiod of 23 h of light (23L) compared with a photoperiod of 14 h of light (14L). Procedures Ten-day-old Nicholas heavy strain poults were exposed to either a 14L or 23L photoperiod. Between 16 and 18 weeks of age, equal numbers of turkeys per treatment group underwent ophthalmic examination (biomicroscopy, indirect ophthalmoscopy) ( n = 14), refractometry ( n = 20), keratometry ( n = 20), tonometry ( n = 20), and full-field electroretinography ( ERG) ( n = 14). Postmortem analyses included orbital magnetic resonance imaging ( MRI) ( n = 10) and light microscopy ( n = 24) at 18 weeks of age. Results Autorefraction revealed a median of −0.13 for sphere in both groups ( P = 0.69), which is approximately emmetropia. The radius of curvature of the cornea was significantly higher ( P = 0.0001) and the refractive power of the cornea was significantly lower ( P = 0.0001) in the 23L group. The astigmatic power was significantly greater in the 23L group ( P = 0.0001). Mean intraocular pressure did not differ between groups ( P = 0.085). Turkeys from the 23L group had significantly larger globes in nasotemporal ( P = 0.0007), dorsoventral ( P = 0.015), and anterioposterior ( P = 0.021) directions, and anterior chambers were more shallow ( P = 0.0002). ERGs revealed the 23L group to have lower a- and b-wave amplitudes and significantly lower cone flicker amplitudes ( P = 0.0008). Light microscopic examination revealed 23L turkeys to have significantly decreased numbers of nuclei in the outer nuclear layer ( P = 0.0001) and inner nuclear layer ( P = 0.0186), and decreased choroidal thickness ( P = 0.0008). The prevalence of cataract in the 23L group was significantly higher ( P = 0.001). Conclusions Exposing turkeys to a prolonged photoperiod induces significant ocular disease. [ABSTRACT FROM AUTHOR]

Objective To investigate diagnostic accuracy of multiphase computed tomography urography ( MCTU) and visual assessment at ureterorenoscopy ( URS) for detection of upper tract urothelial carcinoma ( UTUC). Patients and Methods Consecutive patients referred to our tertiary care centre were included in a prospective study covering the period 2005 to 2012. The patients underwent initial imaging and URS with focal samples taken. Cytopathological results served as reference standard. Results We investigated 174 renal units ( RUs; renal pelvis and adjacent ureter) in 148 patients. UTUC was found in 104 RUs. MCTU had an accuracy of 0.74, sensitivity of 0.89, specificity of 0.51, positive predictive value of 0.73, and negative predictive value of 0.75; corresponding values for URS were 0.84, 0.84, 0.85, 0.89, and 0.78, respectively. MCTU had significantly higher sensitivity and accuracy compared with other imaging techniques ( P<0.05). Compared with MCTU, URS had similar sensitivity but significantly greater specificity and accuracy. Conclusion Both MCTU and URS are important tools in the diagnostic evaluation of UTUC although neither of those techniques achieves 100% accuracy. MCTU should be chosen as the radiographical method if there are no contraindications and URS should always be combined with focal cytology and biopsies of suspicious lesions. To enhance diagnostic precision both MCTU and URS with focal samples should be included in the diagnostic procedure. The present results add impact to current diagnostic guidelines. [ABSTRACT FROM AUTHOR]

Thread-level speculation can be used to take advantage of multicore architectures for JavaScript in web applications. We extend previous studies with these main contributions; we implement thread-level speculation in the state-of-the art just-in-time-enabled JavaScript engine V8 and make the measurements in the Chromium web browser both from Google instead of using an interpreted JavaScript engine. We evaluate the thread-level speculation and just-in-time compilation combination on 15 very popular web applications, 20 HTML5 demos from the JS1K competition, and 4 Google Maps use cases. The performance is evaluated on two, four, and eight cores. The results clearly show that it is possible to successfully combine thread-level speculation and just-in-time compilation. This makes it possible to take advantage of multicore architectures for web applications while hiding the details of parallel programming from the programmer. Further, our results show an average speedup for the thread-level speculation and just-in-time compilation combination by a factor of almost 3 on four cores and over 4 on eight cores, without changing any of the JavaScript source code. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Reactivation of varicella zoster virus ( VZV) can manifest with facial palsy diagnosed as Ramsay Hunt Syndrome ( RHS) or Ramsay Hunt Syndrome zoster sine herpete ( RHS- ZSH). These syndromes are associated with poor prognosis despite treatment with antivirals and corticosteroids. Concentrations of biomarkers such as neurofilament protein ( NFL), S-100β protein and glial fibrillary acidic protein ( GFAp) have previously been measured in cerebrospinal fluid ( CSF) to assess neuronal damage and glial pathology. We employed immunochemical methods to measure concentrations of NFL, S-100β protein and GFAp in CSF from patients with RHS ( n = 15) and RHS- ZSH ( n = 13) diagnosed by detection of VZV DNA in the CSF by quantitative PCR, and compared with a control group ( n = 52). The biomarker concentrations were correlated with CSF viral load and outcome measured by House-Brackmann score. NFL and GFAp concentrations were increased compared with controls ( P = 0.008 and P = 0.04), while S-100β levels were decreased. This pattern was more pronounced in patients with RHS compared to the patients with RHS- ZSH ( NS and P = 0.028). The amount of viral DNA in CSF correlated with increased GFAp ( P = 0.003) and NFL ( P = 0.006). No correlations were found between biomarker concentrations and patient outcome. Patients with facial palsy caused by VZV had biochemical signs of neuronal damage and astrogliosis. High amounts of viral DNA may be associated with the degree of damage on neuronal and astroglial cells. Prospective studies are warranted to elucidate the association of elevated biomarkers in the CSF and outcome assessed by more sensitive tests. [ABSTRACT FROM AUTHOR]

Background & Aims BCAT1 initiates the catabolism of branched-chain amino acids. Here, we investigated the function of BCAT1 and its transcriptional regulatory mechanism in hepatocellular carcinoma ( HCC). Methods RNASeq was used to evaluate BCAT1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT1 in BEL-7404 cells and the suppression of endogenous BCAT1 expression with sh RNA in HepG2 cells, the cell proliferation, clone-forming ability and cell-cycle changes were measured with MTT assay, colony-forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT1 on cancer growth in vivo. Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT1 gene by MYC. The expression of the BCAT1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. Results BCAT1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT1 in BEL-7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S-G2/M phase transition and chemoresistance to cisplatin. The suppression of BCAT1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S-G2/M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT1. Clinical data showed that BCAT1 expression correlated with a significantly poorer prognosis. Conclusion BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC. [ABSTRACT FROM AUTHOR]

Both cat breeders and the lay public have interests in the origins of their pets, not only in the genetic identity of the purebred individuals, but also in the historical origins of common household cats. The cat fancy is a relatively new institution with over 85% of its 40-50 breeds arising only in the past 75 years, primarily through selection on single-gene aesthetic traits. The short, yet intense cat breed history poses a significant challenge to the development of a genetic marker-based breed identification strategy. Using different breed assignment strategies and methods, 477 cats representing 29 fancy breeds were analysed with 38 short tandem repeats, 148 intergenic and five phenotypic single nucleotide polymorphisms. Results suggest the frequentist method of Paetkau (single nucleotide polymorphisms = 0.78, short tandem repeats = 0.88) surpasses the Bayesian method of Rannala and Mountain (single nucleotide polymorphisms = 0.56, short tandem repeats = 0.83) for accurate assignment of individuals to the correct breed. Additionally, a post-assignment verification step with the five phenotypic single nucleotide polymorphisms accurately identified between 0.31 and 0.58 of the misassigned individuals raising the sensitivity of assignment with the frequentist method to 0.89 and 0.92 for single nucleotide polymorphisms and short tandem repeats respectively. This study provides a novel multistep assignment strategy and suggests that, despite their short breed history and breed family groupings, a majority of cats can be assigned to their proper breed or population of origin, that is, race. [ABSTRACT FROM AUTHOR]

The Tabby markings of the domestic cat are unique coat patterns for which no causative candidate gene has been inferred from other mammals. In this study, a genome scan was performed on a large pedigree of cats that segregated for Tabby coat markings, specifically for the Abyssinian ( T a-) and blotched ( t b t b) phenotypes. There was linkage between the Tabby locus and eight markers on cat chromosome B1. The most significant linkage was between marker FCA700 and Tabby ( Z = 7.56, θ = 0.03). Two additional markers in the region supported linkage, although not with significant LOD scores. Pairwise analysis of the markers supported the published genetic map of the cat, although additional meioses are required to refine the region. The linked markers cover a 17-cM region and flank an evolutionary breakpoint, suggesting that the Tabby gene has a homologue on either human chromosome 4 or 8. Alternatively, Tabby could be a unique locus in cats. [ABSTRACT FROM AUTHOR]

Concentrated chemical spills have been shown to impact adversely on fish populations and even cause localized population extinctions. Evaluating population-level impacts of sublethal exposure concentrations is, however, complex and confounded by other environmental pressures. Applying effect measures derived from laboratory-based chemical exposures to impacts in wild fish populations is constrained by uncertainty on how biochemical response measures (biomarkers) translate into health outcomes, lack of available data for chronic exposures and the many uncertainties in available fish population models. Furthermore, wild fish show phenotypic plasticity and local adaptations can occur that adds geographic and temporal variance on responses. Such population-level factors are rarely considered in the chemical risk assessment process and can probably be derived only from studies on wild fish. Molecular technologies, including microsatellite and SNP genotyping, and RNASeq for gene expression studies, are advancing our understanding of mechanisms of eco-toxicological response, tolerance, adaptation and selection in wild populations. We examine critically the application of such approaches with examples including using microsatellites that has identified roach ( Rutilus rutilus) populations living in rivers contaminated with sewage effluents that are self-sustaining, and studies of stickleback ( Gasterosteus aculeatus) and killifish ( Fundulus heteroclitus) that have identified genomic regions under selection putatively related to pollution tolerance. Integrating data on biological effects between laboratory-based studies and wild populations, and building understanding on adaptive responses to sublethal exposure are some of the priority research areas for more effective evaluation of population risks and resilience to contaminant exposure. [ABSTRACT FROM AUTHOR]

Ultra-thin MFI membranes were evaluated for N2/He separation over the temperature range of 85-260 K for the first time. The membranes were rather nitrogen selective at all the conditions investigated. A highest N2/He selectivity of 75.7 with a high N2 flux of 83 kg/m²/h was observed at 124 K. The separation was attributed to adsorption selectivity to N2, effectively hindering the transport of He in the zeolite pores. The exceedingly high permeance even at low temperatures was ascribed to the ultrathin (<1µm) membrane used. As the pressure ratios increased, a better separation performance was obtained. A mathematical model showed the largest difference of adsorbed loading over the film at ca. 120 K was the main reason for the observed maximum selectivity. Further, the modelling indicated the selectivity would increase 2-3 times by reducing the influence of defects, concentration polarization, and pressure drop over the support. [ABSTRACT FROM AUTHOR]

An approximately six-month-old wild American black bear ( Ursus americanus) was found wandering in Saskatchewan and was presented to the Veterinary Medical Centre of the Western College of Veterinary Medicine for apparent blindness. Clinical examination confirmed an inability to navigate a photopic maze, bilateral tapetal hyper-reflectivity, fundi devoid of retinal vessels, and small pale optic nerve papillae. Single-flash electroretinography revealed A and B-wave amplitudes of approximately 40 and 140 microvolts, respectively, in both eyes. Histologic abnormalities included bilateral optic papillary mineralization and bilateral segmental optic nerve degeneration, with occasional intralesional lymphocytes confirmed with immunohistochemistry for CD3+. There was also bilateral multifocal retinal dysplasia, gliosis, lymphocytic retinitis, a complete lack of retinal blood vessels, an intravitreal vascular membrane, and a mild lymphocytic-plasmacytic uveitis with small pre-iridal cellular membranes. The presence of a positive ERG in a blind bear with numerous retinal ganglion cells and degenerative changes in the optic nerve are most consistent with vision loss due to optic nerve injury, which given the young age of the bear likely occurred during ocular development. The presence of ocular inflammation suggests this injury resulted from an inflammatory/infectious process. The etiology could not be determined. Hepatic concentrations of vitamin A were within the normal reference range for domestic species. Pan-herpesvirus PCR and immunohistochemistry for canine distemper virus and Toxoplasma gondii were negative, although this does not rule out these or other infectious etiologies. This represents the first case report of neonatal or congenital ocular abnormalities in an ursid species. [ABSTRACT FROM AUTHOR]