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Background It is important for dermatologists and other physicians in refugee-receiving countries to acquire knowledge of forensic dermatology to identify lesions from torture. Objective Review forensic dermatology in cases of torture. Results In providing medical assessment and care to refugees and migrants, chronic skin lesions will be the most readily identifiable signs of torture. Beatings are very common, with blunt force trauma resulting in post-inflammatory hyperpigmentation. Torture burns can be thermal, chemical or electrothermal, causing distinct lesions determined by the method, duration and intensity of exposure, and area of skin affected. Sharp instruments inflict a wide range of lesions arising from stabbing/perforation or cuts from knives. Wound healing without medical attention and in unsanitary conditions will affect the scarring process. Lesions from suspension and ligatures may occur alongside scars from other forms of torture. Differential diagnoses include self-inflicted wounds, ethnic scarification and scars from traditional healing practices. Conclusion Physicians who may encounter survivors of torture in community or specialist practice would benefit from basic training in forensic dermatology, whilst knowledge of common forms of torture and cultural practices in refugees’ countries of origin is important when considering differential diagnoses of skin lesions.

Objective To investigate whether regional white matter hyperintensities (WMHs) relate to alpha oscillations (AO) in a large population-based sample of elderly individuals. Methods We associated voxel-wise WMHs from high-resolution 3-Tesla MRI with neuronal alpha oscillations (AO) from resting-state multichannel EEG at sensor (N=907) and source space (N=855) in older participants of the LIFE-Adult study (60–80 years). In EEG, we computed relative alpha power (AP), individual alpha peak frequency (IAPF), as well as long-range temporal correlations (LRTC) that represent dynamic properties of the signal. We implemented whole-brain voxel-wise regression models to identify regions where parameters of AO were linked to probability of WMH occurrence. We further used mediation analyses to examine whether WMH volume mediated the relationship between age and AO. Results Higher prevalence of WMHs in the superior and posterior corona radiata was related to elevated relative AP, with strongest correlations in the bilateral occipital cortex, even after controlling for potential confounding factors. The age-related increase of relative AP in the right temporal brain region was shown to be mediated by total WMH volume. Conclusion A high relative AP corresponding to increased regional WMHs was not associated with age per se, in fact, this relationship was mediated by WMHs. We argue that the WMH-associated increase of AP reflects a generalized and likely compensatory spread of AO leading to a larger number of synchronously recruited neurons. Our findings thus suggest that longitudinal EEG recordings might be sensitive to detect functional changes due to WMHs.

BACKGROUND Increasing kyphosis of the spine in a human is a well-recognized clinical phenomenon that has been associated with back pain, poor physical performance and disability. The pathophysiology of age-related kyphosis is complex and has been associated with physiological changes in vertebrae, intervertebral disc (IVD) and paraspinal musculature, which current cross-sectional studies are unable to demonstrate. Creating an in vivo, paraspinal myopathic animal model for longitudinal study of these changes under controlled conditions is thus warranted. PURPOSE To confirm the TSC1 gene knockout effect on paraspinal muscle musculature; to analyze the development of spinal kyphosis, IVD degeneration and vertebra structural changes in a longitudinal manner to gain insights into the relationship between these processes. STUDY DESIGN A prospective cohort study of 28 female mice, divided into 4 groups—9-month-old TSC1mKO (n=7), 9-month-old control (n=4), 12-month-old TSC1mKO (n=8), and 12-month-old controls (n=9). METHODS High resolution micro-computed tomography was used to measure sagittal spinal alignment (Cobb's angle), vertebral height, vertebral body wedging, disc height index (DHI), disc wedge index (DWI), histomorphometry of trabecular bone and erector spinae muscle cross-sectional area. Paraspinal muscle specimens were harvested to assess for myopathic features with H&E stain, muscle fiber size, density of triangular fiber and central nucleus with WGA/DAPI stain, and percentage of fibers with PGC-1α stain. Intervertebral discs were evaluated for disc score using FAST stain. RESULTS Compared to controls, paraspinal muscle sections revealed features of myopathy in TSC1mKO mice similar to human sarcopenic paraspinal muscle. While there was significantly greater presence of small triangular fiber and density of central nucleus in 9-and 12-month-old TSC1mKO mice, significantly larger muscle fibers and decreased erector spinae muscle cross-sectional area were only found in 12-month-old TSC1mKO mice compared to controls. TSC1mKO mice developed accelerated thoracolumbar kyphosis, with significantly larger Cobb angles found only at 12 months old. Structural changes to the trabecular bone in terms of higher bone volume fraction and quality, as well as vertebral body wedging were observed only in 12-month-old TSC1mKO mice when compared to controls. Disc degeneration was observed as early as 9 months in TSC1mKO mice and corresponded with disc wedging. However, significant disc height loss was only observed when comparing 12-month-old TSC1mKO mice with controls. CONCLUSIONS This study successfully shows the TSC1 gene knockout effect on the development of paraspinal muscle myopathy in a mouse which is characteristic of sarcopenia. The TSC1mKO mice is by far the best model available to study the pathological consequence of sarcopenia on mice spine. With paraspinal muscle myopathy established as early as 9 months, TSC1mKO mice developed disc degeneration and disc wedging. This is followed by kyphosis of the spine at 12 months with concomitant disc height loss and vertebral body wedging due to bone remodeling. Age-related bone loss was not found in our study, suggesting osteoporosis and myopathy-induced vertebral body wedging are likely two independent processes. CLINICAL SIGNIFICANCE This is the first study to provide key insights on the early and late consequences of paraspinal myopathy on intervertebral disc degeneration, spinal kyphosis, and vertebral body changes. With this new understanding, future studies evaluating therapies for spinal degeneration may be performed to develop time-sensitive interventions.

Patients with intestinal failure often need long-term home parenteral support (PS). We aimed to determine how the underlying diagnosis, complications and survival had changed over the last 36 years in the UK's largest IF centre.978 adult home PS patient records were analysed from January 1979 until October 2016. The age, sex, underlying aetiology, complications and survival was compared over 5-year periods.Pre-1990 to 2011-2016, numbers increased from 29 to 451, the mean age of patients increased from 31 ± 16.5 to 52 ± 17.6 years. The percentage of patients with IF due to surgical complications increased (3.4%-28.8%, p 0.001)), while those with inflammatory bowel disease decreased (37.9%-22.6%, p 0.001). Complication of home PS reduced: catheter related blood stream infections (CRBSI) 71.4% to 42,2%, CVC thrombosis 34.5%-5.3%. Intestinal failure associated liver disease (IFLAD) 10.3%-1.8%. Patients with dysmotility, scleroderma and a congenital aetiology had the highest incidence of CRBSI and CVC Thrombosis. Overall survival was greater pre-1995 [HR 0.2-0.4 (p = 0.02)] most likely associated with an increase in mean age. Survival for patients without malignancy was 90%, 66%, 55%, 45%, 33% and 25% at 1,5, 10, 15, 20 and 30 years respectively. Multivariate analysis demonstrated a relationship between survival and age of starting home PS; type of home PS; presence or absence of the colon in continuity; and underlying aetiology.Demand for home PS is increasing in particular for advanced malignancy, post-surgical complications and older more co-morbid patients. Complications of home PS are reducing over the last 30 years and 10-year survival for non-malignant aetiologies improving. Survival and changes in aetiology in intestinal failure.

High doses BMP-2 have resulted in a series of complications in spinal fusion. We previously established a polyelectrolyte complex (PEC) carrier system that reduces the therapeutic dose of BMP-2 in both rodent and porcine spinal fusion models. This study aimed to evaluate the safety and efficacy of the combination of bone marrow mesenchymal stem cells (BMSCs) and low dose BMP-2 delivered by PEC for bone regeneration in a porcine model of anterior lumbar interbody spinal fusion (ALIF) application. Six Yorkshire pigs underwent a tri-segmental (L2/L3; L3/L4; L4/L5) ALIF in four groups, namely: (1) BMSCs + 25 μg BMP-2/PEC (n = 9), (2) 25 μg BMP-2/PEC (n = 3), (3) BMSCs (n = 3), and (4) 50 μg BMP-2/absorbable collagen sponge (n = 3). Fusion outcomes were evaluated by radiography, biomechanical testing, and histological analysis after 12 weeks. Mean radiographic scores at 12 weeks were 2.7, 2.0, 1.0, and 1.0 for Groups 1 to 4, respectively. µ-CT scanning, biomechanical evaluation, and histological analysis demonstrated solid fusion and successful bone regeneration in Group 1. In contrast, Group 2 showed inferior quality and slow rate of fusion, and Groups 3 and 4 failed to fuse any of the interbody spaces. There was no obvious evidence of seroma formation, implant rejection, or any other complications in all groups. The results suggest that the combination of BMSCs and low dose BMP-2/PEC could further lower down the effective dose of the BMP-2 and be used as a bone graft substitute in the large animal ALIF model. This article is protected by copyright. All rights reserved.

Objective To report the development of focal bullous retinal detachments (bullae) in dogs with different forms of progressive retinal atrophy (PRA). Procedures Dogs with three distinct forms of PRA (PRA-affected Whippets, German Spitzes and CNGB1-mutant Papillon crosses) were examined by indirect ophthalmoscopy and spectral domain optical coherence tomography (SD-OCT). Retinal bullae were monitored over time. One CNGB1-mutant dog was treated with gene augmentation therapy. The canine BEST1 gene coding region and flanking intronic sequence was sequenced in at least one affected dog of each breed. Results Multiple focal bullous retinal detachments (bullae) were identified in PRA-affected dogs of all three types. They developed in 4 of 5 PRA-affected Whippets, 3 of 8 PRA-affected Germans Spitzes and 15 of 20 CNGB1-mutant dogs. The bullae appeared prior to marked retinal degeneration and became less apparent as retinal degeneration progressed. Bullae were not seen in any heterozygous animals of any of the types of PRA. Screening of the coding region and flanking intronic regions of the canine BEST1 gene failed to reveal any associated pathogenic variants. Retinal gene augmentation therapy in one of the CNGB1-mutant dogs appeared to prevent formation of bullae. Conclusions Retinal bullae were identified in dogs with three distinct forms of progressive retinal atrophy. The lesions develop prior to retinal thinning. This clinical change should be monitored for in dogs with PRA.

The proportion of Thoroughbred (TB) horses that commence training and eventually race, is an important industry-level indicator of how successful it is at producing horses suitable for racing. It is also of interest to the wider community and is central to the issue of whether there is overbreeding in the Australian TB industry. This study investigated the training and racing records for the 2005 and 2010 Victorian TB foal crops to determine the proportion of TBs that train and race, and the age of entering training and first race start. Subsets of the foal crop were also examined to determine if premier yearling sale cohorts would produce selection bias. The Australian Stud Book (ASB) registered 7662 TB horses born in Victoria in 2005 (n = 4116) and 2010 (n = 3546). Of these, 5614 (73%) entered training and 4868 (64%) started in at least one race. Fourteen percent (n = 1045) of the study cohort had their first race start as 2-year-olds and 35% (n = 2644) had their first start as 3-year-olds. A higher proportion of TB horses that attended premier yearling sales entered training (93%) and raced (84%). This study established a baseline for training and racing milestones, such as the proportion and age that horses commenced training, and age of first start using population-level data. It also established that the use of subsets of the population can introduce selection bias.

Behçet’s disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients’ origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women’s group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG (p p = 0.017) and females (p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population.

Objectives Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI. Methods We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 ± 9.0 years, patients-at-risk, and all GOLD groups) from one center of the “COSYCONET” COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu’s method, k-means clustering, texture analysis, and 80th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRMEmph) and functional small airway disease (PRMfSAD), and FEV1/FVC from PFT. Results All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p r = 0.72, p p Emph (r = 0.70 to 0.75, p Emph (mean difference = 35.85 to 40.40) and PRMfSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = − 0.54 to − 0.41, p Conclusion QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRMEmph and PRMfSAD. We propose to use QDP based on Otsu’s method for future clinical studies in COPD. Key Points • QDP quantified from DCE-MRI is associated with visual MRI perfusion score, CT PRM indices, and PFT. • The extent of QDP from DCE-MRI corresponds to the combined extent of PRMEmph and PRMfSAD from CT. • Assessing pulmonary perfusion abnormalities using DCE-MRI with QDP improved the correlations with CT PRM indices and PFT compared to the quantification of pulmonary blood flow and volume.

Perceptual-cognitive-motor skills, such as visual anticipation, are pivotal for superior performance in sport. However, there are only a limited number of skill acquisition specialists working with...

This article analyses news sources used by women to discuss the COVID-19 pandemic on the UK parenting website Mumsnet. By using a non-political online ‘third space’ aimed at women, Mumsnetters are able to avoid the aggression women face when they attempt to discuss news in the wider public sphere of the Internet. This third space can also act as a ‘trusted friend’, allowing women to access important news via a third party. Mumsnetters’ discussion of the news around COVID-19 complicates previous studies’ findings that women prefer to discuss news relating to health, education and the local community rather than politics and international affairs. Mumsnetters discuss the COVID-19 pandemic as both a health story and a political story. They use mainly digital journalism sources, either directly from the mainstream news media or indirectly via social media such as Twitter, thus participating in a hybrid media system. However, some Mumsnet discussants demonstrate a hostility and distrust towards mainstream news sources, even suggesting collusion between the media and the UK government, which has implications for the clear dissemination of government messages around the pandemic.

Acute myocarditis is a serious, likely underdiagnosed condition affecting people of all ages and for which the number of UK hospital admissions is rising. A primary diagnosis of myocarditis accounted for 0.04% (36.5 per 100,000) of all hospital admissions in England between 1998 and 2017, although this is likely to be an underestimate of the true burden of myocarditis. The aetiology is broad, including infective and inflammatory conditions as well as exposure to toxic agents. Clinical features are varied and overlap with other acute cardiac conditions making diagnosis a challenge. Cardiovascular magnetic resonance imaging currently serves as the gold standard non-invasive diagnostic modality. If an underlying aetiological process is identified, then therapy may be directed at the cause; however, for most, treatment is supportive and aimed at managing any complications such as heart failure or arrhythmias. There is emerging evidence for immunosuppressive therapy in certain cases. Prognosis is generally good with recovery in most; however, up to 30% with biopsy-proven myocarditis progress to develop a dilated cardiomyopathy and its potential associated complications. All-cause mortality in the UK for patients presenting to hospital with acute myocarditis is approximately 4%.

Meeting the 2035 WHO targets of reducing tuberculosis incidence by 90% from 2015 levels requires the implementation of country-specific tuberculosis control strategies. This systematic review aims to identify factors that facilitate or impede the implementation of such strategies in EU and European Economic Area (EEA) settings. Focusing on providers of care, health system constraints, and social and political factors, this Review complements available evidence on the accessibility of tuberculosis services to recipients of care. Databases were searched for EU and EEA articles published between Jan 1, 1997, and Nov 6, 2020, that presented empirical data on tuberculosis policies, strategies, guidelines, or interventions. 2061 articles were screened and 65 were included. The most common barrier to tuberculosis control strategies described the divergence of health-care practices from guidelines, often related to inadequate knowledge or perceived usefulness of the guidelines by clinicians. The most commonly identified enabler to tuberculosis control strategies was the documented positive attitudes of health-care workers towards tuberculosis programmes. Divergence between clinical practice and guidelines was described in most EU and EEA settings, indicating the need for a focused review of guideline adherence. Strengths of this study involve its broad inclusion criteria and wide range of tuberculosis control strategies analysed.

Brain-age (BA) estimates based on deep learning are increasingly used as neuroimaging biomarker for brain health; however, the underlying neural features have remained unclear. We combined ensembles of convolutional neural networks with Layer-wise Relevance Propagation (LRP) to detect which brain features contribute to BA. Trained on magnetic resonance imaging (MRI) data of a population-based study (n=2637, 18-82 years), our models estimated age accurately based on single and multiple modalities, regionally restricted and whole-brain images (mean absolute errors 3.37-3.86 years). We find that BA estimates capture aging at both small and large-scale changes, revealing gross enlargements of ventricles and subarachnoid spaces, as well as white matter lesions, and atrophies that appear throughout the brain. Divergence from expected aging reflected cardiovascular risk factors and accelerated aging was more pronounced in the frontal lobe. Applying LRP, our study demonstrates how superior deep learning models detect brain-aging in healthy and at-risk individuals throughout adulthood.

Purpose Stroke is one of the most prevalent vascular diseases. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and follow alterations of receptor expression and metabolism in ischemic stroke. The aim of this study was to assess the cannabinoid type 2 receptor (CB2R) levels in transient middle cerebral artery occlusion (tMCAO) mouse models at subacute stage using positron emission tomography (PET) with our novel tracer [18F]RoSMA-18-d6 and structural imaging by magnetic resonance imaging (MRI). Procedures Our recently developed CB2R PET tracer [18F]RoSMA-18-d6 was used for imaging neuroinflammation at 24 h after reperfusion in tMCAO mice. The RNA expression levels of CB2R and other inflammatory markers were analyzed by quantitative real-time polymerase chain reaction using brain tissues from tMCAO (1 h occlusion) and sham-operated mice. [18F]fluorodeoxyglucose (FDG) was included for evaluation of the cerebral metabolic rate of glucose (CMRglc). In addition, diffusion-weighted imaging and T2-weighted imaging were performed for anatomical reference and delineating the lesion in tMCAO mice. Results mRNA expressions of inflammatory markers TNF-α, Iba1, MMP9 and GFAP, CNR2 were increased to 1.3–2.5 fold at 24 h after reperfusion in the ipsilateral compared to contralateral hemisphere of tMCAO mice, while mRNA expression of the neuronal marker MAP-2 was markedly reduced to ca. 50 %. Reduced [18F]FDG uptake was observed in the ischemic striatum of tMCAO mouse brain at 24 h after reperfusion. Although higher activity of [18F]RoSMA-18-d6 in ex vivo biodistribution studies and higher standard uptake value ratio (SUVR) were detected in the ischemic ipsilateral compared to contralateral striatum in tMCAO mice, the in vivo specificity of [18F]RoSMA-18-d6 was confirmed only in the CB2R-rich spleen. Conclusions This study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18F]FDG measure of CMRglc in the ischemic striatum of tMCAO mice at subacute stage. [18F]RoSMA-18-d6 might be a promising PET tracer for detecting CB2R alterations in animal models of neuroinflammation without neuronal loss., Molecular Imaging and Biology, 24 (5), ISSN:1860-2002, ISSN:1536-1632

Observational studies with long-term follow-up of patients with primary central nervous system lymphoma (PCNSL) are scarce. Patient data over a period of four decades were retrospectively analysed from databases at Not-tingham University Hospitals Trust, UK. The cohort was delineated by two distinct therapeutic eras; the first from 01/01/1982 to 31/12/2010 (n = 147) and the second 01/01/2011 to 31/07/2020 (n = 125). The median age at diagnosis was significantly older in the second era compared to the first (69 and 65 years respectively, P = 0·003). The 3-, 6-and 12-month overall survival (OS) rates in the second era were significantly higher compared to the first, at 85%, 77%, 62% versus 56%, 49%, 38% respectively (log-rank test P < 0·0001). On multivariate analysis, high-dose methotrexate (HD-MTX)-based induction protocols employed in the second era were associated with improved OS compared to those used in the first [hazard ratio (HR) 0·40, 95% confidence interval (CI) 0·28–0·57]. Within the second era, superior OS rates were seen with the use of intensive HD-MTX protocols (including consolidation with high-dose chemotherapy and autologous stem cell transplantation) compared to non-intensive HD-MTX schedules (HR 0·47, 95% CI 0·22–0·99). Initiating chemotherapy within 14 days of biopsy and use of rituximab were independently associated with improved OS and progression-free survival during the second era. These data suggest that prompt treatment initiation and use of intensive HD-MTX-and rituximab-based protocols have resulted in improved survival outcomes for patients.

In response to a published national payer survey indicating striking needs for multistakeholder initiatives to increase biosimilar adoption, a focus workgroup meeting joining payers and providers was conducted in December 2019 in Boston, MA. Before the focus group meeting, a survey was sent to health care providers to collect perceptions about barriers to biosimilar adoption and gather input on best potential strategies for addressing these barriers. The focus group panel consisted of 5 managed care pharmacists and 3 physician experts in rheumatology, dermatology, and gastroenterology, representing large managed care organizations and health care systems in the Boston area. A clinical moderator facilitated discussions between the payers and providers regarding challenges to biosimilar adoption and potential collaborative strategies to overcome these barriers. The focus group participants identified hurdles to biosimilar adoption in 3 major areas: (1) the lack of confidence in biosimilar interchangeability and a need for education about biosimilars, (2) the lack of financial incentives to switch to biosimilars from the reference biologic product, and (3) administrative burdens that impair the prescription of biologics. Learning from their mutual experiences, the focus group participants formulated action plans to address these barriers. The top strategies recommended by the participants included advancing biosimilar education, facilitating administrative processes related to biosimilar prescriptions, and increasing provider reimbursement while reducing cost sharing to patients receiving biosimilars.

We report the first published case of Prototheca wickerhamii breast implant infection. This occurred after mastectomy, chemotherapy, radiotherapy, breast reconstruction, implant revisions and breast seroma aspirations and was preceded by polymicrobial infection. Definitive treatment required implant removal and intravenous liposomal amphotericin B. The management of breast prosthesis infections is discussed., Highlights • Clinical update on breast implant infections. • Algae can cause chronic infections that persist despite broad-spectrum therapy. • Consider removal of prostheses to assist with source control. • Biofilm-active agents are useful adjuncts in prosthetic infections. • Adherence to principles of surgical site infection prevention is recommended.

Psoriasis is polygenic, interleukin (IL)-17 and IL-23 driven chronic relapsing inflammatory multisystem disease caused by a complex interplay of endogenous and environmental factors. The most common and distressing symptom in psoriasis is itch, adding significantly to the burden of disease. Although histamine has historically not been considered a key itch mediator in psoriasis, there is some evidence from the literature that antihistamines may be effective to reduce itch in psoriasis. This review focuses on the role of antihistamines in the management of itch in psoriasis. The literature search included peer-reviewed articles published in English language (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) until January 2021 and by reference lists of respective articles. J Drugs Dermatol. 2021;20(8):844-847. doi:10.36849/JDD.5966.

Chronic psychosocial stress is increasingly being recognised as a risk factor for sporadic Alzheimer's disease (AD). The hypothalamic-pituitary-adrenal axis (HPA axis) is the major stress response pathway in the body and tightly regulates the production of cortisol, a glucocorticoid hormone. Dysregulation of the HPA axis and increased levels of cortisol are commonly found in AD patients and make a major contribution to the disease process. The underlying mechanisms remain poorly understood. In addition, within the general population there are interindividual differences in sensitivities to glucocorticoid and stress responses, which are thought to be due to a combination of genetic and environmental factors. These differences could ultimately impact an individuals' risk of AD. The purpose of this review is first to summarise the literature describing environmental and genetic factors that can impact an individual's HPA axis reactivity and function and ultimately AD risk. Secondly, we propose a mechanism by which genetic factors that influence HPA axis reactivity may also impact inflammation, a key driver of neurodegeneration. We hypothesize that these factors can mediate glucocorticoid priming of the immune cells of the brain, microglia, to become pro-inflammatory and promote a neurotoxic environment resulting in neurodegeneration. Understanding the underlying molecular mechanisms and identifying these genetic factors has implications for evaluating stress-related risk/progression to neurodegeneration, informing the success of interventions based on stress management and potential risks associated with the common use of glucocorticoids.

Purpose The purpose of this paper is to explore the impact of the Diversity Project, a cross company initiative that has been applied in the investment and savings profession to accelerate progress towards a more inclusive culture across the industry. This is with a view to providing a template for other industries considering impactful change. Design/methodology/approach This paper considers the approach taken by the investment and savings industry to drive change towards a more inclusive culture by using a summative content analysis approach. The authors framework this application using Sustainable Development Goal 10 (reduced inequalities) to increase relevance and contribution beyond this context. Findings The Diversity Project demonstrates numerous examples of driving change within the investment and savings industry by galvanising cross company support for events, publications, charters and action. These experiences will provide policymakers and practitioners in other industrial sectors insight to achieve similar change. Originality/value The Diversity Project established in 2016 has gained significant traction in the investment and savings industry through membership of 70 firms and 30 partner firms, supporting 18 cross company diversity and inclusion work streams focussed on developing collaborative and cohesive action plans.

In this work, the impact of positive bias stress (PBS) on an all copper(Cu)-electrode a-InGaZnO TFT is discussed. Commonly, Cu diffusion from the source/drain electrode after negative bias stress (NBS) leads to degradations in the on-state current and subthreshold swing. However, this study finds that diffusion in the gate insulator layer from the gate electrode suffers from more serious degradation. Eventually, this phenomenon causes a serious breakdown of the gate insulator such that it loses the transistor function. Results indicate that after 2000s of PBS, accumulation of Cu ions forms a filament which dominates the leakage path. During the stress duration, the gate leakage current is monitored and current fittings are adopted to confirm the phenomena. Furthermore, temperature dependencies have verified the results of hopping and Ohmic conduction at different stages of deterioration. Compared to previous literature that focus on the impacts of source/drain electrodes, this work suggests that gate engineering for thin film transistors is more urgent for high-quality display applications.

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer’s disease dementia (AD)) as an ‘Inception cohort’ who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an ‘Enrichment cohort’ (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

Elite athletes suffer many mental health symptoms and disorders at rates equivalent to or exceeding those of the general population. COVID-19 has created new strains on elite athletes, thus potentially increasing their vulnerability to mental health symptoms. This manuscript serves as a narrative review of the impact of the pandemic on management of those symptoms in elite athletes and ensuing recommendations to guide that management. It specifically addresses psychotherapy, pharmacotherapy and higher levels of care. Within the realm of psychotherapy, crisis counselling might be indicated. Individual, couple/family and group psychotherapy modalities all may be helpful during the pandemic, with novel content and means of delivery. Regarding pharmacotherapy for mental health symptoms and disorders, some important aspects of management have changed during the pandemic, particularly for certain classes of medication including stimulants, medications for bipolar and psychotic disorders, antidepressants and medications for substance use disorders. Providers must consider when in-person management (eg, for physical examination, laboratory testing) or higher levels of care (eg, for crisis stabilisation) is necessary, despite potential risk of viral exposure during the pandemic. Management ultimately should continue to follow general principles of quality health care with some flexibility. Finally, the current pandemic provides an important opportunity for research on new methods of providing mental health care for athletes, and consideration for whether these new methods should extend beyond the pandemic. [Abstract copyright: © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.]

Background Severity of disease and outcomes in patient with COVID-19 has been associated with several risk factors tied to the metabolic syndrome. Aims We conducted a study with the objective of describing the association between the baseline Fibrosis-4 (FIB-4) index prior to SARS-CoV-2 infection and the severity of COVID-19 among patients at risk of non-alcoholic fatty liver disease (NAFLD). Methods This was a retrospective cohort study of patients with at least two risk factors for metabolic syndrome diagnosed with COVID-19. The main exposure of interest was FIB-4 index prior to infection, categorized into three previously validated age-specific levels. The main outcomes of interest were disease requiring hospitalization and in-hospital mortality. Results We included 373 patients [median age, 62 years; 194 male (52%); median number of metabolic syndrome risk factors, 3]. The median FIB-4 index was 1.10 (interquartile range 0.78–1.61). In models adjusting for diabetes mellitus and chronic kidney disease, patients with intermediate FIB-4 index had 67% higher odds of hospitalization compared to those in the low category {odds ratio (OR) 1.67 [(95% CI 1.06–2.64); p = 0.03]} and patients with high FIB-4 index had higher odds of mortality compared to intermediate and low category with an OR 2.22 (95% CI 1.20–4.12; p = 0.01). However, when we evaluated components of FIB-4 (age and AST/ALT ratio), we found that age alone was the best predictor of hospitalization and mortality. Conclusions Among patients at risk of NAFLD with COVID-19 infection, elevated pre-infection FIB-4 index was associated with worsened clinical outcomes, but age was the strongest predictor. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-07120-0.

Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (

The N-methyl-D-aspartate receptor (NMDAR) plays a crucial role in neurodegenerative diseases such as Alzheimer’s disease and in the treatment of major depression by new fast-acting antidepressants such as ketamine. Given their broad implications, GluN2B-containing NMDARs have been of large interest as diagnostic and therapeutic targets. Recently, (R)-11C-Me-NB1 was investigated preclinically and shown to be a promising radioligand for imaging GluN2B subunits. Here, we report on the performance characteristics of this novel radioligand in a first-in-human PET study. Methods: Six healthy male subjects were scanned twice on a fully-integrated PET/MR scanner with (R)-11C-Me-NB1 for 120 min. Brain uptake and tracer distribution over time were investigated by standardized uptake values (SUV). Test-retest reliability was assessed with the absolute percentage difference (APD) and the coefficient of variation (COV). Exploratory total volumes of distribution (VT) were computed using an arterial input function and the Logan plot as well as a constrained two-tissue compartment model with K1/k2 coupled (2TCM). SUV was correlated with VT to investigate its potential as a surrogate marker of GluN2B expression. Results: High and heterogeneous radioligand uptake was observed across the entire gray matter with reversible kinetics within the scan time. SUV APD ranged from 6.8 - 8.5% and COV from 4.9 - 6.0%, indicating a high test-retest reliability. A moderate correlation was found between SUV averaged from 70-90 min and VT using Logan plot (Spearman’s rho = 0.44). Correlation between VT Logan and 2TCM was r= 0.76. Conclusion: The novel radioligand, (R)-11C-Me-NB1, was highly effective in mapping GluN2B-enriched NMDARs in the human brain. With a heterogeneous uptake and a high test-retest reliability, this radioligand offers promise to deepen our understanding of the GluN2B-containing NMDA receptor in the pathophysiology and treatment of neuropsychiatric disease such as Alzheimer’s disease and major depression. Additionally, it could help in the selection of appropriate doses of GluN2B-targeting drugs. ISSN:0097-9058 ISSN:0022-3123 ISSN:0161-5505 ISSN:2159-662X ISSN:1535-5667

Background There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1 (TE)) depends on the echo-time (TE) and reflects regional pulmonary function. Purpose To investigate the potential diagnostic value of T1 (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT. Study type Prospective non-randomized diagnostic study. Population Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference. Field strength/sequence Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for T1 (TE) mapping at TE1-5 = 70 μsec, 500 μsec, 1200 μsec, 1650 μsec, and 2300 μsec. Assessment Perfusion images were scored by three radiologists. T1 (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired. Statistical tests Spearman rank correlation coefficients (ρ) were calculated between T1 (TE) and perfusion scores, clinical parameters and qCT. A P-value Results Median values were T1 (TE1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2 , with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ -0.69) were found. Overall, correlations were strongest at TE2 , weaker at TE1 and rarely significant at TE4 -TE5 . Data conclusion In COPD patients, the increase of T1 (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1 (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T1 (TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE. Level of evidence 2 TECHNICAL EFFICACY: Stage 1.

In this letter, a study of physical mechanisms is introduced to describe an abnormal phenomenon in transfer characteristics while p-type low-temperature polycrystalline silicon thin-film transistors (LTPS TFTs) were subjected to a negative bias temperature stress (NBTS) in an illuminated environment. In general, under NBTS, the transfer characteristics exhibits a negative shift of threshold voltage and a degradation of subthreshold swing. Here, however, experimental results reveal that the degree of degradation is different after NBTS is applied to poly-silicon TFTs in a darkened and in an ultraviolet condition. This variation is mainly a result of the light-generated electrons recombining with the inversed holes, and leading to a lower degree of degradation. Moreover, we found that the influence of the UV light is an edge effect at different channel lengths. This letter investigates the illumination effect in LTPS TFTs during NBTS, and the phenomenon is clarified by electrical measurements and by trap state extraction.

Substantial challenges must be addressed to simulate food processing operations including realistic prediction of liquid and solid mixing, fragmentation of solids and liquids, multiphase behaviour, and interactions with complex machinery geometries. A particle-based modelling approach is presented which comprises Smoothed Particle Hydrodynamics (SPH) representations of continua (liquids and solids), coupled with Discrete Element Model (DEM) representations of discrete components such as solid particulates and bubbles. The simulation framework is demonstrated for six example applications that are common in food manufacturing and that are difficult to model with other numerical approaches. Simulations are presented for liquid mixing in a planetary mixer of fluids of varied viscosity, solid particulate blending in a ribbon blender, particle size reduction of almonds fragmented in a food processor, sieving of fine cohesive flour, multiphase flow of ice and liquid in a Slushie machine, and delivery of post-mix soft drink including bubble and foam generation. Each of these example applications are discussed in context of the needs of the simulation for improving process and the benefits of the particle-based modelling approach.

PurposeAlthough there is growing academic and business interest in autism employment programs, few studies have examined employee (manager and coworker) attitudes toward these programs. The purpose of this study is to examine the impact of workload changes (a job demand) and perceived supervisor support (a job resource) on commitment to the program and employee engagement more broadly.Design/methodology/approachA total of 229 employees from two Australian public sector organizations completed a survey about the autism employment program in their organization.FindingsPerceived workload increases were associated with lower affective commitment and higher continuance commitment to the program. Perceived supervisor support was associated with higher affective commitment to the program and employee engagement, but lower continuance commitment to the program. Perceived supervisor support moderated the effect of workload increase on employee engagement, but not in the expected direction.Originality/valueThis research helps to fill a gap in the autism employment literature by focusing on commitment toward autism employment programs among existing employees. The research helps to provide a more complete and nuanced view of these programs within their broader organizational context.

BACKGROUND Phototherapy has been a mainstay therapy for dermatological diseases since more than a century. Although phototherapy is still extensively used and some recommendations exist, only scarce data are available addressing disease-specific differences in cumulative doses, treatment durations and costs. Knowledge of such differences could help to avoid over-/undertreatment, predict treatment duration and costs. Therefore, we sought to determine differences in cumulative doses, numbers of sessions, side effects and costs among different skin diseases and genders in real-life conditions. METHODS In this single-centre, retrospective study, patients treated with phototherapy between March 2014 and April 2019 were classified into seven diagnostic groups and analysed according to the study goals. RESULTS Out of 561 patients (age 53.9 ± 20.3 yrs; 52.9% females), 83.7% percent were treated with cabin NB-UVB (mean cumulative dose 17.79 ± 17.11 J/cm2 ). Patients with vitiligo and psoriasis were treated with significantly higher cumulative NB-UVB doses (cabin, local) in comparison with the five other diagnostic groups as were males in comparison with females. Consequently, significantly higher UV-related costs resulted in patients with vitiligo, psoriasis and males. Patients with atopic dermatitis and pruritus were treated with significantly higher cumulative UVA1 doses compared to patients with non-atopic eczema. The complication rate (pooled from all UV modalities) in our population was 3.8% (erythema 3.4%, aggravated itch 0.4% and worsening of symptoms 0.2%). CONCLUSIONS Our results demonstrate that cumulative doses and phototherapy-related costs vary strongly among skin diseases-a fact not adequately considered in recommendations. A more disease-specific stratification of phototherapy could not only help to optimize outcomes, but also to facilitate comparability of clinical trials using phototherapy.

BACKGROUND AND PURPOSE: SWI hypointense cerebral lesions have been reported in adults with the inherited cerebellar neurodegenerative disorder ataxia telangiectasia. This study aims to establish the prevalence, age-dependency, and spatial distribution of these lesions in children and young people with ataxia telangiectasia. MATERIALS AND METHODS: Participants with classic ataxia telangiectasia and matched controls underwent SWI acquisition at 3T at 1 or 2 time points. SWI hypointense lesions were manually labeled according to the Microbleed Anatomical Rating Scale. Differences in prevalence of lesion number between groups with ataxia telangiectasia and without ataxia telangiectasia were tested with the Fisher exact test, and differences in age between participants with ataxia telangiectasia with and without lesions were tested using independent samples from the Mann-Whitney U test. The relationship between age and lesion number was modeled as an exponential function. RESULTS: Analyzable SWI datasets from 17 participants with ataxia telangiectasia (with median age at first scan of 12.4 years; range, 4.6–20.2 years; 8 [47%] were female) and 22 matched healthy controls showed prevalence of SWI hypointense lesions in 41% of participants with ataxia telangiectasia and 0% in controls (P = .001, the Fisher exact test). Lesions were exclusively supratentorial and predominantly lobar. Participants with ataxia telangiectasia with SWI hypointense lesions were older than those without (median age was 15.2 years versus 9.3 years, U = 10.5, P = .014). An exponential curve described the relationship between age and lesion number (R2 = 0.67). CONCLUSIONS: SWI hypointense lesions are common in children and young people with ataxia telangiectasia, accumulating from 12 years of age onward. In contrast to cerebellar-dominant neurodegeneration in ataxia telangiectasia, SWI hypointense lesions were exclusively supratentorial. Further investigation is needed to establish the clinical relevance of these imaging-detected lesions.

Background Cervical smear cytology and colposcopic biopsy histology are prone to error at both collection and interpretation stages, leading to a large number of discordant cases. Aims Investigation of five-year outcomes for women who have cervical cytology that is discordant and higher grade than histology results. Materials and methods A retrospective cohort study was carried out for 111 women with cervical cytology discordant and higher grade than histology, after cytopathological review, over a three-year period. Five-year follow-up data were reviewed to identify the highest level of pathology seen within five years from the discordance. Results Women with atypical squamous cells with possible high-grade change (ASC-H) cytology and negative biopsy (n = 28) had a 46% chance of high-grade histological disease within 5 years; with cervical intraepithelial neoplasia grade 1 (CIN1) histology (n = 20), this was reduced to 30%. With high-grade cytology and negative histology (n = 23), 48% had high-grade disease within five years, including one case of invasive disease; with CIN1 histology 50% had high-grade disease within five years. Conclusions This study demonstrates a 30-50% chance of high-grade disease within five years, in the setting of ASC-H or high-grade cytology with a negative or low-grade colposcopic biopsy. This highlights that in the setting of cytology and histology discordance, at least one of the tests indicating high-grade pathology warrants the need for treatment or close ongoing surveillance.

Objectives To assess physical activity (PA), mental health and well-being of adults in the United Kingdom (UK), Ireland, New Zealand and Australia during the initial stages of National governments’ Coronavirus disease (COVID-19) containment responses. Design Observational, cross-sectional. Methods An online survey was disseminated to adults (n = 8,425; 44.5 ± 14.8y) residing in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government-mandated COVID-19 restrictions. Main outcome measures included: Stages of Change scale for exercise behaviour change; International Physical Activity Questionnaire (short-form); World Health Organisation-5 Well-being Index; and the Depression Anxiety and Stress Scale-9. Results Participants who reported a negative change in exercise behaviour from before initial COVID-19 restrictions to during the initial COVID-19 restrictions demonstrated poorer mental health and well-being compared to those demonstrating either a positive-or no change in their exercise behaviour (p < 0.001). Whilst women reported more positive changes in exercise behaviour, young people (18-29y) reported more negative changes (both p < 0.001). Individuals who had more positive exercise behaviours reported better mental health and well-being (p < 0.001). Although there were no differences in PA between countries, individuals in New Zealand reported better mental health and well-being (p < 0.001). Conclusion The initial COVID-19 restrictions have differentially impacted upon PA habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage PA should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation.

This study presents computational fluid dynamics (CFD) analysis of the effects of wettability, viscosity and interfacial tension (IFT) for enhanced oil recovery (EOR) with varying pore configuration. A more realistic pore-throat geometry is studied which was motivated by oil-containing rock configuration that indicates the importance of pore geometry in EOR. The results are compared with those obtained for a simple geometry. Both saturated and unsaturated conditions are considered while the IFT varies. For both geometries, the saturated condition presents 99% of oil recovery, for the water-wet and intermediate states while it is about 88% for the oil-wet state. However, there is a significant difference in the temporal evolution of the oil recovery factor, as the complex model is 1.4 to 3 times slower than the simplified one to achieve maximum oil recovery factor under the same conditions. For unsaturated conditions, two different initial oil volumes were considered to explore the combined effect of low IFT and change in wettability. Similarly, the oil recovery process is significantly slower for the complex geometric configuration. The study of very low IFT values (10, 35, 65 and 75 µN/m) for the complex configuration in the unsaturated oil condition revealed that highest oil recovery is achieved at the IFT of 75 µN/m. The results confirm that geometric configuration plays an important role in EOR. The impact of pore structure becomes more significant in the unsaturated oil state demonstrating that very low values of IFT slow the oil recovery process.

This work studies the effect of the location of the light shielding (LS) layer on negative bias illumination stress (NBIS) instability in self-aligned top-gate amorphous indium-gallium-zinc oxide thin-film transistors (SA-TG a-InGaZnO TFTs). Although the NBIS instability can be mitigated by introducing a fully covered LS layer, it causes an unwanted parasitic capacitance, as evidenced by capacitance–voltage ( ${C}$ – ${V}$ ) measurements. An alternative solution, in which the device that is partially covered by the LS layer at the source side, is proposed to optimize the tradeoff. This study suggests that an LS layer could be adopted in the SA-TG configuration, as it is versatile in different structural designs, depending on the requirement of targeted applications.

Background Endocrinopathic laminitis develops in association with insulin dysregulation, but the role of insulin in the pathogenesis remains unclear. Hyperinsulinemia can cause hypoaminoacidemia, which is associated with integumentary lesions in other species and therefore warrants investigation as a potential mechanism in laminitis. Objective Evaluate plasma amino acid concentrations in the euglycemic‐hyperinsulinemic clamp (EHC) and prolonged glucose infusion (PGI) laminitis models. Animals Sixteen Standardbred horses. Methods Prospective experimental study. Plasma amino acid concentrations were measured in samples collected every 6 hours from horses that underwent a 48‐hour EHC (n = 8) or 66‐hour PGI (n = 8) after a 24‐ or 6‐hour baseline period in EHC and PGI groups, respectively. Results Fifteen of the 20 measured amino acid concentrations decreased over time in both EHC and PGI horses (P

This paper describes the process of engaging young people in a user centred, co-design strategy to define their perfect condom. Our aims were 1) to find a way to destigmatise discussions about sexu...

This study focuses on the interaction between the oxide layer area of a transistor and its ferroelectric layer area. An experimental comparison of transistor oxide layer area demonstrates that the larger the ratio of oxide to ferroelectric layers, the larger the on/off ratio, thus improving performance. A subsequent experiment aimed to further demonstrate this in different sized devices, and changing the ratio of $\text{A}_{\text {HZO}}/\text{A}_{\text {SiO2}}$ (the area of HfZrOx divided by oxide layer) showed the same tendency as above, but also produced an unexpected finding in that a comparison of on/off ratio exhibits an abnormal electric characteristic. This study discusses this abnormal electric characteristic and proposes an explanatory physical model.

Objective Posttraumatic stress disorder (PTSD) following interpersonal trauma in transitional-aged youth (TAY), aged 15 to 25, is highly prevalent; however, evidence-based interventions have rarely been studied. Method A single-group pre-/posttest study was conducted at headspace Sunshine, Melbourne, Australia, evaluating the feasibility, acceptability, safety, tolerability, and potential clinical effectiveness of trauma-focused cognitive-behavioral therapy (TF-CBT). Results An intent-to-treat analysis was conducted for N = 20 participants (65% female, n = 13) who attended a mean of 15 TF-CBT sessions over 25 weeks. At the end of treatment, only 1 of the 16 participants with a baseline PTSD diagnosis still met diagnostic criteria. Significant improvements were also noted for self-report measures of PTSD (d = -.83), anxiety (d = -.74), and depression (d = -.76). A minority of participants reported a brief exacerbation in symptoms of PTSD (n = 8) and anxiety and depression (n = 5) during stabilization and directly before and/or after the trauma-narration phase. However, all symptoms resolved at the end of treatment. The majority of participants (85%, n = 17) rated the intervention as helpful. Conclusion Regardless of the expected temporary symptom exacerbation, the results indicated that TF-CBT was safe, tolerable, and acceptable. Transitional-aged youth is an emerging area of research. With limited research available on this age group to inform evidence-based practice, it is recommended that a randomized controlled trial is conducted to determine if TF-CBT (Cohen et al., 2017) can be effectively translated to this underresearched age group. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Mentalizing, or reflective functioning, refers to the capacity to reflect on one's own and others' mental states in terms of desires, intentions, and feelings. Reflective functioning in men's mental health is poorly understood, particularly in reference to men's resilience and motivation for personal growth. Using a cross-sectional design, the present study investigated impaired reflective functioning in relation to resilience and personal growth initiative among men with mental health concerns. An online sample of 1065 men self-reporting mental health concerns completed measures of reflective functioning, psychological distress, resilience, and personal growth initiative. Logistic regression examined reflective functioning in relation to likely serious mental illness, including interaction with age. Subsequent regression analyses controlled for distress severity in examining associations with resilience and personal growth initiative, and in examining the potential mediating role of reflective functioning. Impaired reflective functioning was significantly associated with serious psychological distress irrespective of age and, after controlling for distress severity, with resilience and personal growth initiative. Moreover, impaired reflective functioning was a significant mediator of the relationship between resilience and personal growth initiative. Findings provide preliminary support for reflective functioning as salient to men's resilience and agency for personal change, indicating a potentially important target in men's mental health work.

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer’s disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ɛ4 and rs11023139 in individuals with high amyloid-β burden. APOE ɛ4/rs11023139-A carriers declined significantly faster than APOE ɛ4/rs11023139-G_G carriers in measures of global cognition (p = 0.011) and verbal episodic memory (p = 0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ɛ4 cognitively normal older adults with a high neocortical amyloid-β burden.

OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI.METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI.RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30 U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 pCONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.

Background There is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function. Methods Ninety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO2peak. Results First, the exercise intervention was found to increase cardiorespiratory fitness (VO2peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants. Conclusion At the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity.

BackgroundPhysical inactivity has been consistently linked to increased risk of cognitive decline; however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements; however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition.MethodsThis multi-arm pilot randomised clinical trial investigated the effects of 6 months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12 months post-intervention. Ninety-nine cognitively normal men and women (aged 60–80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e. high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test.ResultsThere was a dose-dependent effect of exercise intensity on cardiorespiratory fitness, whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition.ConclusionsWe did not observe a direct effect of exercise on cognition. Future work in this field should be appropriately designed and powered to examine factors that may contribute to individual variability in response to intervention.Trial registrationThis study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered on 3 May 2017—retrospectively registered.https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780

COVID-19 has created unprecedented organisational challenges, yet no study has examined the impact on information search. A case study in a knowledge-intensive organisation was undertaken on 2.5 million search queries during the pandemic. A surge of unique users and COVID-19 search queries in March 2020 may equate to ‘peak uncertainty and activity’, demonstrating the importance of corporate search engines in times of crisis. Search volumes dropped 24% after lockdowns; an ‘L-shaped’ recovery may be a surrogate for business activity. COVID-19 search queries transitioned from awareness, to impact, strategy, response and ways of working that may influence future search design. Low click through rates imply some information needs were not met and searches on mental health increased. In extreme situations (i.e. a pandemic), companies may need to move faster, monitoring and exploiting their enterprise search logs in real time as these reflect uncertainty and anxiety that may exist in the enterprise.