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BACKGROUND Women with HIV face challenges in engaging in HIV care post partum. We aimed to examine changes in engagement in HIV care through clinic attendance before, during, and after pregnancy, compared with matched women with HIV who had never had a recorded pregnancy. METHODS In this cohort study, we describe changes in engagement in HIV care before, during, and after pregnancy among women with HIV from the UK Collaborative HIV Cohort (CHIC) study from 25 HIV clinics in the UK with a livebirth reported to the National Surveillance of HIV in Pregnancy and Childhood between Jan 1, 2000, and Dec 31, 2017. To investigate whether changes were specific to HIV, we compared these changes to those over equivalent periods among non-pregnant women with HIV in the UK CHIC study matched for ethnicity, year of conception, age, CD4 cell count, viral suppression, and antiretroviral therapy use. Analyses were via logistic regression using generalised estimated equations with an interaction between case-control status (pregnant women vs non-pregnant women) and pregnancy or pseudo pregnancy (for non-pregnant women) stage. FINDINGS 1116 matched pairs of pregnant and non-pregnant women were included (median age 34 years [IQR 30-38], 80·1% Black African, 12·5% white). 69 330 person-months of follow-up were recorded, 25 412 in the before stage, 18 897 during, and 25 021 after pregnancy or pseudo pregnancy stages. Among pregnant women, the proportion of time engaged in care increased during pregnancy (8477 [90·5%] of 9371 person-months) and after pregnancy (10 501 [84·6%] of 12 407), compared with before pregnancy (9979 [78·5%] of 12 707). Among non-pregnant women in the control group, engagement in HIV care remained stable across the three equivalent stages (9688 [76·3%] of 12 705 person-months before pseudo pregnancy; 7463 [78·3%] of 9526 during pseudo pregnancy; and 9892 [78·4%] of 12 614 after pseudo pregnancy). The association of engagement in HIV care with pregnancy or pseudo pregnancy stage differed significantly by case-control status (pinteraction

RATIONALE, AIMS AND OBJECTIVES: Applying traditional industrial quality improvement (QI) methodologies to primary care is often inappropriate because primary care and its relationship to the healthcare macrosystem has many features of a complex adaptive system (CAS) that is particularly responsive to bottom-up rather than top-down management approaches. We report on a demonstration case study of improvements made in the Family Health Center (FHC) of the JPS Health Network in a refugee patient population that illustrate features of QI in a CAS framework as opposed to a traditional QI approach. METHODS: We report on changes in health system utilization by new refugee patients of the FHC from 2016 to 2017. We review the literature and summarize relevant theoretical understandings of quality management in complex adaptive systems as it applies to this case example. RESULTS: Applying CAS principles in the FHC, utilization of the Emergency Department and Urgent Care Center by newly arrived refugee patients before their first clinic visit was reduced by more than half (total visits decreased from 31%-14% of the refugee patients). Our review of the literature demonstrates that traditional algorithmic top-down QI processes are most often unsuccessful in improving even a few single-disease metrics, and increases clinician burnout and penalizes clinicians who care for vulnerable patients. Improvement in a CAS occurs when front-line clinicians identify care gaps and are given the flexibility to learn and self-organize to enable new care processes to emerge, which are created from bottom-up leadership that utilize existing interdependencies and interact with the top levels of the organization through intelligent top-down causation. We give examples of early adapters who are better applying the principles of CAS change to their QI efforts. CONCLUSIONS: Meaningful improvement in primary care is more likely achieved when the impetus to implement change shifts from top-down to bottom-up.

Objectives Determine if outpatient physiotherapy care via telerehabilitation is as effective as in-person physiotherapy care after total hip replacement. Design Randomised, single-blind, controlled, non-inferiority clinical trial. Setting QEII Jubilee Hospital, Brisbane, Australia. Participants Seventy patients receiving a total hip replacement entered the study, sixty-nine completed the study. Interventions The control group (n = 35; x ¯ age 67; female 60%) received in-person outpatient physiotherapy and a paper-based home exercise programme. The intervention group (n = 35; x ¯ age 62; female 66%) received remotely delivered telerehabilitation directly into their homes and a technology-based home exercise program using an iPad application. Main outcome measures The primary outcome was the quality of life subscale of the Hip disability and Osteoarthritis Outcome Score measured at six weeks post-operatively. Secondary outcomes included objective strength and balance outcomes, self-reported function and satisfaction outcomes, and home exercise program compliance. Results No between group difference was detected in the Hip disability and Osteoarthritis Outcome Score quality of life subscale at the primary end point of six weeks (P = 0.970). Strength, balance and self-reported function showed no between group differences. Overall satisfaction was high across both groups, with the intervention group scoring higher for ease of attending appointments (intervention 95 (10), control 86 (18), mean difference 9 (95% CI 2 to 16), P = 0.017. The intervention group were more compliant with their home exercise programme (intervention 86% (20%), control 74% (26%), mean difference 12% (95% CI 1% to 23%), P = 0.048). Conclusions Telerehabilitation programmes can be delivered to total hip replacement patients in their own homes, using readily available technology while maintaining high levels of satisfaction. More importantly, telerehabilitation patients appear to achieve non-inferior physical and functional outcomes as those receiving in-person rehabilitation programmes. Trial Registration : ACTRN12615000824561. (Australian New Zealand Clinical Trials Registry).

Background and aims Among treatment-naive individuals with chronic hepatitis C viral (HCV) infection and without cirrhosis, glecaprevir/pibrentasvir for 8 weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir/pibrentasvir for 6 weeks in people with acute and recent HCV infection. Approach and results In this open-label, single-arm, multicenter, international pilot study, adults with recent HCV (duration of infection 10 × upper limit of normal) or anti-HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months of enrollment and evidence of prior spontaneous or treatment-induced clearance. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Thirty men (median age 43 years, 90% men who have sex with men) received treatment, of whom 77% (n = 23) were human immunodeficiency virus-positive, 47% (n = 14) had ever injected drugs, and 13% (n = 4) had HCV reinfection. The majority had HCV genotype 1 (83%, n = 25), followed by genotype 4 (10%, n = 3) and genotype 3 (7%, n = 2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention-to-treat and per-protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse, and there were two cases of nonvirological failure (death, n = 1; loss to follow-up, n = 1). No treatment-related serious adverse events were seen. Conclusions Glecaprevir/pibrentasvir for 6 weeks was highly effective among people with acute and recent HCV infection, supporting further evaluation of shortened-duration pan-genotypic therapy in this setting.

Objective\udHIV-remission strategies including kick-and-kill could induce viral transcription and immune-activation in the central nervous system, potentially causing neuronal injury. We investigated the impact of kick-and-kill on plasma neurofilament light (NfL), a marker of neuro-axonal injury, in RIVER trial participants commencing antiretroviral treatment (ART) during primary infection and randomly allocated to ART-alone or kick-and-kill (ART + vaccination + vorinostat (ART + V + V)).\ud\udDesign\udSub-study measuring serial plasma NfL concentrations.\ud\udMethods\udPlasma NfL (using Simoa digital immunoassay), plasma HIV-1 RNA (using single-copy assay) and total HIV-1 DNA (using quantitative polymerase chain reaction in peripheral CD4+ T-cells) were measured at randomisation (following ≥22 weeks ART), week 12 (on final intervention day in ART + V + V) and week 18 post-randomisation. HIV-specific T-cells were quantified by intracellular cytokine staining at randomisation and week 12. Differences in plasma NfL longitudinally and by study arm were analysed using mixed models and Student's t-test. Associations with plasma NfL were assessed using linear regression and rank statistics.\ud\udResults\udAt randomisation, 58 male participants had median age 32 years and CD4+ count 696 cells/μL. No significant difference in plasma NfL was seen longitudinally and by study arm, with median plasma NfL (pg/mL) in ART-only vs ART + V + V: 7.4 vs 6.4, p = 0.16 (randomisation), 8.0 vs 6.9, p = 0.22 (week 12) and 7.1 vs 6.8, p = 0.74 (week 18). Plasma NfL did not significantly correlate with plasma HIV-1 RNA and total HIV-1 DNA concentration in peripheral CD4+ T-cells at any timepoint. While higher HIV-specific T-cell responses were seen at week 12 in ART + V + V, there were no significant correlations with plasma NfL. In multivariate analysis, higher plasma NfL was associated with older age, higher CD8+ count and lower body mass index.\ud\udConclusions\udDespite evidence of vaccine-induced HIV-specific T-cell responses, we observed no evidence of increased neuro-axonal injury using plasma NfL as a biomarker up to 18 weeks following kick-and-kill, compared with ART-only.

Trauma can lead to widespread vascular dysfunction, but the underlying mechanisms remain largely unknown. Inward-rectifier potassium channels (Kir2.1) play a critical role in the dynamic regulation of regional perfusion and blood flow. Kir2.1 channel activity requires phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid that is degraded by phospholipase A2 (PLA2) in conditions of oxidative stress or inflammation. We hypothesized that PLA2-induced depletion of PIP2 after trauma impairs Kir2.1 channel function. A fluid percussion injury model of traumatic brain injury (TBI) in rats was used to study mesenteric resistance arteries 24 h after injury. The functional responses of intact arteries were assessed using pressure myography. We analyzed circulating PLA2, hydrogen peroxide (H2O2), and metabolites to identify alterations in signaling pathways associated with PIP2 in TBI. Electrophysiology analysis of freshly-isolated endothelial and smooth muscle cells revealed a significant reduction of Ba2+-sensitive Kir2.1 currents after TBI. Additionally, dilations to elevated extracellular potassium and BaCl2- or ML 133-induced constrictions in pressurized arteries were significantly decreased following TBI, consistent with an impairment of Kir2.1 channel function. The addition of a PIP2 analog to the patch pipette successfully rescued endothelial Kir2.1 currents after TBI. Both H2O2 and PLA2 activity were increased after injury. Metabolomics analysis demonstrated altered lipid metabolism signaling pathways, including increased arachidonic acid, and fatty acid mobilization after TBI. Our findings support a model in which increased H2O2-induced PLA2 activity after trauma hydrolyzes endothelial PIP2, resulting in impaired Kir2.1 channel function.

This paper summarizes the overall results of the VIII World Engineering Education Forum, X Global Engineering Deans Council, XIV Global Student Forum, held in November 2018 in Albuquerque, NM USA, and discusses the emerging global collaboration for Peace Engineering (PEng) and Peace Engineering education. The theme of this first ever global conference on Peace Engineering was in tune with global events and developments. Participants were a confluence of practitioners, researchers, policy makers and educators from all over world, encompassing academia, multinational industry, US national labs and multilateral organizations. Results from a formal survey show that participants rated the conference as very good or excellent in all aspects and asked for more coverage of the topic of Peace Engineering and teaching material and strategies that embody Peace Engineering learning and teaching. The Conference succeeded in catalyzing conversations and idea exchanges for concrete plans for the next steps to advance a movement for Peace Engineering education, including • A Global Peace Engineering minor • Peace Engineering Certificate program • Master of Science in Peace Engineering • Database of Peace Engineering case studies • Workshops and other forums to promote discussion and planning for Peace Engineering programs and curricula • Data models, metrics, analytics and simulations: fine grain to large grain • Development of Peace Engineering as the new global engineering mindset Participants were engaged and enthusiastic about the concept and a Peace Engineering movement was born, along with the idea of creating a Peace Engineering Consortium.

The creation of the Peace Engineering Consortium is an outcome of the First Global Peace Engineering Conference, held November 2018 in Albuquerque NM, USA (www.weef-gedc2018.org). A team of conference participants are collaborating to develop the Peace Engineering Consortium. That is, to define and implement its charter, identify initiatives and preliminary activities, and continue to identify definitions of what Peace Engineering (PEng) – or Engineering for Peace – is. PEng is a call for action, in a new mindset not only for engineering, but for all existing and future disciplines to address global challenges. Current activities are: • Curricula and content – Members are collaborating to define, create and share curricula for undergraduate minors, professional certificate programs and graduate work; Creating experiential laboratories with industry and practitioner partners; Facilitating information exchange and the symmetry of information/knowledge through globally accessible digital libraries; Incorporating engineering diplomacy, diversity and cultural awareness (including the arts, music and language) into the practice for peacebuilding, peacemaking and peacekeeping. • Research and Development - The group is focused on collaborations, both domestic and international, and internal initiatives that advance the state of Peace Engineering. Key areas of focus have been developing metrics, data models, analytics, visualization and prediction. Some key initiatives include developing a modelling and visualizing conflict, Peace Data Standard, and pollution mitigation. • Entrepreneurial and Economic Development – The consortium is pursuing entrepreneurial activities in peace technology. It has been invited to produce a special edition on Peace Engineering and Innovation in the high impact Technological Forecasting and Social Change journal. • Events – In its charter year, the consortium organized a summer institute at The Hague and Peace Engineering workshops in Colombia – both models for future global workshops. • Case Studies – Members are compiling and publishing case studies and collaborating with US National Laboratories, industry, and governments to create scalable Peace Engineering case studies.

Transient receptor potential vanilloid family member 4 (TRPV4) transcript and protein expression increased in the urinary bladder and lumbosacral dorsal root ganglia of transgenic mice with chronic urothelial overexpression of nerve growth factor (NGF-OE). We evaluated the functional role of TRPV4 in bladder function with open-outlet cystometry, void spot assays, and natural voiding (Urovoid) assays with the TRPV4 antagonist HC-067047 (1 μM) or vehicle in NGF-OE and littermate wild-type (WT) mice. Blockade of TRPV4 at the level of the urinary bladder significantly ( P ≤ 0.01) increased the intercontraction interval (2.2-fold) and void volume (2.6-fold) and decreased nonvoiding contractions (3.0-fold) in NGF-OE mice, with lesser effects (1.3-fold increase in the intercontraction interval and 1.3-fold increase in the void volume) in WT mice. Similar effects of TRPV4 blockade on bladder function in NGF-OE mice were demonstrated with natural voiding assays. Intravesical administration of HC-067047 (1 µM) significantly ( P ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in littermate WT mice. Blockade of urinary bladder TRPV4 or intravesical infusion of brefeldin A significantly ( P ≤ 0.01) reduced (2-fold) luminal ATP release from the urinary bladder in NGF-OE and littermate WT mice. The results of the present study suggest that TRPV4 contributes to luminal ATP release from the urinary bladder and increased voiding frequency and pelvic sensitivity in NGF-OE mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population. OBJECTIVES: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD. METHODS: Cases with biopsy-proven NAFLD and HIV monoinfection were age and sex-matched to HIV-positive and HIV-negative controls. Markers of bacterial translocation [lipopolysaccharide-binding protein (LBP), bacterial DNA and lipopolysaccharide (LPS)], adipose tissue dysfunction (leptin, adiponectin) and monocyte activation (sCD14 and sCD163) were measured by ELISA. Hepatic patterns of macrophage activation were explored with immunohistochemistry. 16 s rRNA sequencing was performed with stool. RESULTS: Thirty-three cases were included (≥F2 fibrosis n = 16), matched to HIV-positive (n = 29) and HIV-negative (n = 17) controls. Cases with NAFLD were more obese (BMI 31.0 ± 4.4 vs. 24.1 ± 2.8 kg/m, P

In the urinary bladder, mechanosensitive ion channels (MSCs) underlie the transduction of bladder stretch into sensory signals that are relayed to the PNS and CNS. PIEZO1 is a recently identified MSC that is Ca2+ permeable and is widely expressed throughout the lower urinary tract. Recent research indicates that PIEZO1 is activated by mechanical stretch or by pharmacological agonism via Yoda1. Aberrant activation of PIEZO1 has been suggested to play a role in clinical bladder pathologies like partial bladder outlet obstruction and interstitial cystitis/bladder pain syndrome (IC/BPS). In the present study, we show that intravesical instillation of Yoda1 in female Wistar rats leads to increased voiding frequency for up to 16 hours after administration compared to vehicle treatment. In a cyclophosphamide (CYP) model of cystitis, we found that the gene expression of several candidate MSCs (Trpv1, Trpv4, Piezo1, and Piezo2) were all upregulated in the urothelium and detrusor following chronic CYP-induced cystitis, but not acute CYP-induced cystitis. Functionally with this model, we show that Ca2+ activity is increased in urothelial cells following PIEZO1 activation via Yoda1 in acute and intermediate CYP treatment, but not in naïve (no CYP) nor chronic CYP treatment. Lastly, we show that activation of PIEZO1 may contribute to pathological bladder dysfunction through the downregulation of several tight junction genes in the urothelium including claudin-1, claudin-8, and zona occludens-1. Together, these data suggest that PIEZO1 activation plays a role in dysfunctional voiding behavior and may be a future, clinical target for the treatment of pathologies like IC/BPS.

ObjectivesWith the goal of facilitating the use of HIV-TRePS to optimize therapy in settings with limited healthcare resources, we aimed to develop computational models to predict treatment responses accurately in the absence of commonly used baseline data.MethodsTwelve sets of random forest models were trained using very large, global datasets to predict either the probability of virological response (classifier models) or the absolute change in viral load in response to a new regimen (absolute models) following virological failure. Two ‘standard’ models were developed with all baseline variables present and 10 others developed without HIV genotype, time on therapy, CD4 count or any combination of the above.ResultsThe standard classifier models achieved an AUC of 0.89 in cross-validation and independent testing. Models with missing variables achieved AUC values of 0.78–0.90. The standard absolute models made predictions that correlated significantly with observed changes in viral load with a mean absolute error of 0.65 log10 copies HIV RNA/mL in cross-validation and 0.69 log10 copies HIV RNA/mL in independent testing. Models with missing variables achieved values of 0.65–0.75 log10 copies HIV RNA/mL. All models identified alternative regimens that were predicted to be effective for the vast majority of cases where the new regimen prescribed in the clinic failed. All models were significantly better predictors of treatment response than genotyping with rules-based interpretation.ConclusionsThese latest models that predict treatment responses accurately, even when a number of baseline variables are not available, are a major advance with greatly enhanced potential benefit, particularly in resource-limited settings. The only obstacle to realizing this potential is the willingness of healthcare professions to use the system.

Dementia resulting from small vessel diseases of the brain (SVDs) is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type-1 receptor blocker, did not. We attribute this drug class effect to losartan-induced 'aldosterone breakthrough', a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type-1 receptor blockers.

Cerebral small vessel diseases (SVDs) are a central link between stroke and dementia-two comorbidities without specific treatments. Despite the emerging consensus that SVDs are initiated in the endothelium, the early mechanisms remain largely unknown. Deficits in on-demand delivery of blood to active brain regions (functional hyperemia) are early manifestations of the underlying pathogenesis. The capillary endothelial cell strong inward-rectifier K+ channel Kir2.1, which senses neuronal activity and initiates a propagating electrical signal that dilates upstream arterioles, is a cornerstone of functional hyperemia. Here, using a genetic SVD mouse model, we show that impaired functional hyperemia is caused by diminished Kir2.1 channel activity. We link Kir2.1 deactivation to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid essential for Kir2.1 activity. Systemic injection of soluble PIP2 rapidly restored functional hyperemia in SVD mice, suggesting a possible strategy for rescuing functional hyperemia in brain disorders in which blood flow is disturbed.

Subarachnoid hemorrhage (SAH) is a common form of hemorrhagic stroke associated with high rates of mortality and severe disability. SAH patients often develop severe neurological deficits days after ictus, events attributed to a phenomenon referred to as delayed cerebral ischemia (DCI). Recent studies indicate that SAH-induced DCI results from a multitude of cerebral circulatory disturbances including cerebral autoregulation malfunction. Cerebral autoregulation incorporates the influence of blood pressure (BP) on arterial diameter in the homeostatic regulation of cerebral blood flow (CBF), which is necessary for maintaining constant brain perfusion during physiological swings in systemic BP. In this study, we quantitatively examined the impact of SAH on cerebral autoregulation using a mouse endovascular perforation model and a newly developed approach combining absolute and relative CBF measurements. This method enables a direct quantitative comparison of cerebral autoregulation between individual animals (e.g., SAH vs. control or sham-operated mice), which cannot be done solely using relative CBF changes by laser Doppler flowmetry. Here, absolute CBF was measured via injection of fluorescent microspheres at a baseline BP. In separate groups of animals, in vivo laser Doppler flowmetry was used to measure relative CBF changes over a range of BP using phlebotomy and the pressor phenylephrine to lower and raise BP, respectively. Absolute CBF measurements from microspheres were then used to calibrate laser Doppler measurements to calculate the relationship between CBF and BP, i.e., “cerebral autoregulation curves.” Un-operated and sham-operated groups exhibited similar cerebral autoregulatory curves, showing comparable levels of relatively constant CBF over a range of BP from ~80 mmHg to ~130 mmHg. In contrast, SAH animals exhibited a narrower autoregulatory range of BP, which was primarily due to a decrease in the upper limit of BP whereby cerebral autoregulation was maintained. Importantly, SAH animals also exhibited a marked decrease in CBF throughout the entire range of BP. In sum, this study provides evidence of the dramatic reduction in cortical CBF and the diminished range of autoregulation after SAH. Furthermore, this novel methodology should pave the way for future studies examining pathological mechanisms and/or therapeutic strategies targeting impaired cerebral autoregulation, a pathology common to many cardiovascular and cerebrovascular disorders.

Objective: Cardiovascular disease (CVD) primary prevention guidelines recommend absolute CVD risk estimation to guide blood pressure and lipid therapy recommendations but are inconsistent despite relying on similar evidence. This study aimed to compare the populations recommended for treatment according to guidelines in Australia, England and the United States. Methods: Cross-sectional analysis of national health survey data from Australian, English and United States (n = 4,056; n = 2,994; n = 2,943; respectively) adults aged ≥40 years. Participants were classified as recommended for therapy based on clinical characteristics denoting high risk and absolute CVD risk stratification according to each country’s guidelines [1–6]. Agreement in therapy recommendation assessed by Kappa statistic. Results: Agreement in therapy recommendation was minimal to weak (κ = 0.35–0.54). Proportions recommended for either blood pressure or lipid lowering treatment ranged between 26–32%, 47–52% and 43–47% in Australia, England and United States. There was minimal to strong agreement in therapy recommendation according to clinical criteria (κ = 0.38–0.83) and minimal to moderate agreement according to absolute CVD risk (κ = 0.28–0.64) across guidelines. Conclusion: Despite similar evidence apparently underpinning guidance, there is little agreement in the populations targeted for CVD primary prevention with Australia recommending far few people for treatment in comparison to England or the United States. This is due to differences in both clinical characteristics considered high risk and absolute CVD risk stratification. Whilst different countries may adopt different policies on the appropriate level of risk to target, these findings suggest a need to develop international consensus definition for high CVD risk in primary prevention guideline

the IEEE Xplore database, Web of Science and indexed by EI Compendex and ISI Proceedings; One of the major contributions of social manufacturing is in the realm of sustainability. The apparel industry is a good example to assess contribution of social manufacturing to improve sustainability in practice. Value chains in the apparel industry are faced with various challenges regarding sustainability issues. Apparel companies pay higher attention to economic sustainability issues, and environmental and social sustainability issues of the apparel industry are often underrated. We realize that the apparel brand owners have the highest impact on improving the sustainability of the apparel industry. Thus, we design a collaborative business model empowered with social manufacturing to join the forces among the brand owners for improving sustainability of the apparel industry throughout the value chain. We chose a case study of shifting from conventional screen-printing to more environmentally sustainable digital textile printing. We suggest that this shift can be accelerated if the brand owners join theirforces together to shift from conventional printing to digital printing technology in the apparel industry.

We discuss our experiences using Google Colaboratory (Colab), a hosted version of Jupyter Notebooks, in undergraduate artificial intelligence (AI) courses at two universities. Colab was designed for AI and data science researchers to share reproducible experiments and explanations of techniques, but we have also found it well suited to classroom use. The primary benefit is that it provides students computational resources sufficient to run modern AI techniques interactively, and avoids students needing to separately configure software packages and dependencies, since they can run notebooks shared by the instructor. We briefly outline two of our notebooks, for teaching deep learning with Tensorflow, and reinforcement learning with OpenAI Gym.

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects.

Total hip replacement (THR) is the gold standard treatment for severe hip osteoarthritis. Theeffectiveness of physical rehabilitation for THR patients following discharge from hospital issupported by evidence; however, barriers such as geographical location and transport can limitaccess to appropriate health care. One solution is an alternative model of care usingtelerehabilitation technology to deliver rehabilitation programs directly into patients’ homes.Research investigating telerehabilitation for the postoperative management of orthopaedicconditions has yielded promising results. To date, the majority of research has focused on thetotal knee replacement (TKR) population. Multiple randomised controlled trials (RCT) havecompared telerehabilitation programs to conventional programs for postoperative rehabilitationin TKR patients 1-3. Piqueras 1, Russell 2 and Tousignant 3 all demonstrated thattelerehabilitation programs can produce equivalent clinical outcomes compared to in-personprograms in the TKR population. There are no published trials investigating telerehabilitationin the THR population.This thesis aimed to explore current practice and an alternative telerehabilitation mode ofservice delivery following THR. The thesis starts with a national survey (study one) to establishcurrent physiotherapy practice for outpatient THR rehabilitation in Australia. Study twoinvestigated the feasibility of telerehabilitation in the THR and TKR population with respect toconsumer access, and their preferences towards using technology for rehabilitation. These twostudies informed the control and intervention rehabilitation programs for study three, arandomised controlled non-inferiority trial comparing traditional care to telerehabilitation.Finally, a cost-effectiveness study (study four) was conducted comparing the two groups fromstudy three, the RCT.The national survey (study one) revealed that current THR rehabilitation practice in Australiaconsists of the following: patients are referred for outpatient physiotherapy following hospitaldischarge, programs involve three to four total sessions of physiotherapy at a frequency of oneto two times per fortnight; programs commence within two weeks of hospital discharge and lastfive to six weeks; physiotherapy sessions include strengthening of hip abductors and extensors,hip and knee flexors, education on hip precautions and exercise progression, gait re-training,stairs practice, range of motion (ROM) exercises for hip abduction, extension and flexion;physiotherapy sessions are complemented by a home exercise program (HEP). This was the first published national Australian study documenting current rehabilitation practice afterhospital discharge for THR patients. Establishing current practice enables future trials toexplore alternative THR rehabilitation models via comparative studies. Current practice,defined by study one, were adopted as the control (traditional care) rehabilitation program forthe RCT.The feasibility study (study two) provided evidence that post-operative telerehabilitation in theTHR and TKR populations is feasible with respect to access to appropriate technology andconsumer preference for using technology for rehabilitation. To maximise uptake of programs,healthcare providers looking to implement telerehabilitation should consider patients’ age,access to technology at home, training requirements, and preferences for technology.Healthcare providers should consider the need to: provide equipment (especially to patientsaged 66 years and older); train patients in use of technology to increase familiarity and uptake;utilise phone communication where possible, considering the needs of both healthcare providerand patient; and employ exercise-based programs that utilise videos that patients can view athome. The results of this study can be used to consider the practicalities of implementingtelerehabilitation and help inform the planning and configuration of future telerehabilitationservices. In the same way that study one informed the control rehabilitation program for theRCT, findings from study two were critical to the development of the telerehabilitation(intervention) program for the RCT.Study three, a non-inferiority RCT comparing traditional in-person post-operative rehabilitationto a home-based telerehabilitation intervention, showed that telerehabilitation programs can bedelivered to THR patients in their own homes, using readily available technology whilemaintaining high levels of satisfaction. More importantly, telerehabilitation appeared to achievenon-inferior physical and functional outcomes compared to in-person rehabilitation. Study 4demonstrated that in addition to achieving non-inferior outcomes, telerehabilitation in the THRpopulation is of comparable cost-effectiveness to traditional in-person care, and significantlyreduces the time burden of patients and carers.In summary, this thesis provides new information on current practice for THR rehabilitationand offers evidence that telerehabilitation is feasible in this population. The findingsdemonstrate that telerehabilitation achieves non-inferior clinical outcomes while maintaininghigh levels of patient satisfaction. Additionally, it suggests telerehabilitation is of comparablecost-effectiveness to traditional in-person care and significantly reduces patient and carer timeburden. Telerehabilitation in the THR population has the potential to improve access and convenience for patients. This research may enable healthcare services to adopttelerehabilitation for THR patients as a contemporary, evidence-based, cost-effective, patient-centred model of care.

Social stress causes profound urinary bladder dysfunction in children that often continues into adulthood. We previously discovered that the intensity and duration of social stress influences whether bladder dysfunction presents as overactivity or underactivity. The transient receptor potential vanilloid type 1 (TRPV1) channel is integral in causing stress-induced bladder overactivity by increasing bladder sensory outflow, but little is known about the development of stress-induced bladder underactivity. We sought to determine if TRPV1 channels are involved in bladder underactivity caused by stress. Voiding function, sensory nerve activity, and bladder wall remodeling were assessed in C57BL/6 and TRPV1 knockout mice exposed to intensified social stress using conscious cystometry, ex vivo afferent nerve recordings, and histology. Intensified social stress increased void volume, intermicturition interval, bladder volume, and bladder wall collagen content in C57BL/6 mice, indicative of bladder wall remodeling and underactive bladder. However, afferent nerve activity was unchanged and unaffected by the TRPV1 antagonist capsazepine. Interestingly, all indices of bladder function were unchanged in TRPV1 knockout mice in response to social stress, even though corticotrophin-releasing hormone expression in Barrington’s Nucleus still increased. These results suggest that TRPV1 channels in the periphery are a linchpin in the development of stress-induced bladder dysfunction, both with regard to increased sensory outflow that leads to overactive bladder and bladder wall decompensation that leads to underactive bladder. TRPV1 channels represent an intriguing target to prevent the development of stress-induced bladder dysfunction in children.

Background/Aims: Literature supports outpatient physiotherapy rehabilitation following total hip replacement. Current physiotherapy practice for this patient cohort is unknown. This study aimed to establish current physiotherapy practice for outpatient total hip replacement rehabilitation in Australia, and compare current practice with clinical evidence. Methods: An online self-administered questionnaire was designed to reveal current practice for physiotherapy rehabilitation following hospital discharge of total hip replacement patients. The questionnaire was distributed to 151 Australian physiotherapists involved in the care of total hip replacement patients. Findings: A response rate of 77% (116/151) was obtained. Current practice consists of: referral for outpatient physiotherapy, three to four sessions of physiotherapy at a frequency of one to two times a fortnight; commence within two weeks of hospital discharge and last five to six weeks. They include strengthening, education on hip precautions and exercise progression, gait retraining, stairs practice, range of motion exercises. Physiotherapy sessions are complemented by a home exercise programme. Conclusions: The high rate of referral for outpatient physiotherapy and provision of home exercise programmes are evidence-based. The infrequent use of resistance in strength training does not align with current evidence. There is insufficient literature regarding content, timing, frequency and duration to advise whether current practice regarding these aspects is evidence-based.

Investments that are classified as Level 2 within the fair value hierarchy account for approximately 92 percent of US banks' fair value assets. We report an experiment that examines how experienced auditors apply current PCAOB guidance when auditing portfolios of these assets. We hypothesize and find that, depending on how overstatement is distributed within a portfolio, current PCAOB guidance leads auditors to make adjustments that are predictably larger or smaller than the aggregate overstatement in the portfolio. Auditors are more likely to follow PCAOB guidance when doing so leads to lower audit adjustments and higher client income. We also predict and find that auditors identify some patterns of overstatement as indicative of management bias, but not others. However, management-bias assessments do not affect auditors' adjustment decisions as standards imply they should, even when auditors are prompted to consider management bias. Together, these results highlight a potential deficiency in current auditing guidance that managers could exploit by strategically locating overstatements within securities with larger book values or by spreading those overstatements across many securities within a portfolio. We suggest changes to current PCAOB guidance which may reduce these effects.

BACKGROUND: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo. METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed. RESULTS: Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56). CONCLUSIONS: Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

BACKGROUND: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear. METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage. RESULTS: A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P

Pituitary adenylate cyclase-activating polypeptide (PACAP; AdcyaP1) and its cognate PAC1 receptor (Adcyap1r1), have tissue-specific distributions in the lower urinary tract (LUT). The afferent limb of the micturition reflex is often compromised following bladder injury, disease and inflammatory conditions. We have previously demonstrated that PACAP signaling contributes to increased voiding frequency and decreased bladder capacity with cystitis. Thus, the present studies investigated the sensory components (e.g., urothelial cells, bladder afferent nerves) of the urinary bladder that may underlie the pathophysiology of aberrant PACAP activation. We utilized bladder-pelvic nerve preparations and urothelial sheet preparations to characterize PACAP-induced bladder afferent nerve discharge with distention and PACAP- induced Ca(2+) activity, respectively. We determined that PACAP38 (100 nM) significantly (p ≤ 0.01) increased bladder afferent nerve activity with distention that was blocked with a PAC1/VPAC2 receptor antagonist PACAP6–38 (300 nM). PACAP38 (100 nM) also increased Ca(2+) activity in urothelial cells over that observed in control preparations. Taken together, these results establish a role for PACAP signaling in bladder sensory components (e.g., urothelial cells, bladder afferent nerves) that may ultimately facilitate increased voiding frequency.

Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits.Therapy-naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1 : 1 basis to standard ART (Arm1: tenofovir-emtricitabine and atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine and darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in cognitive function across treatment arms with factors associated with cognitive function changes also assessed.Of 60 individuals randomized (30 Arm1 and 30 Arm2), 58 were men and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4 cell count 428 (209) and 414 (229) cells/μl, Arms1 and 2, respectively. At week 48, plasma HIV RNA was less than 50 copies/ml in 55 of 56 of those completing study procedures. Cognitive function improved over 48 weeks [mean change z-score (SD) 0.16 (0.09) Arm1 and 0.25 (0.08) Arm2, P = 0.96 for differences between study arms]. A greater increase in frontal grey matter N-acetyl aspartate/creatine ratio was observed in Arm1 [ratio change of 0.071 (SD 0.16)] versus Arm2 [change -0.097 (SD 0.18), P = 0.009], although this was not associated with changes in cognitive function (P = 0.17).Maraviroc-intensified ART had no demonstrable benefit on cognitive function in individuals initiating ART. Greater improvement in neuronal metabolites (N-acetyl aspartate/creatine) was observed with standard ART. Future work should focus on maraviroc-intensified ART in individuals with cognitive impairment.

This paper examines audit team leader reactions to auditors who speak up about potentially important audit issues. Study 1 is a survey of interacting audit teams and provides evidence of higher performance evaluations for auditors who speak up. Studies 2, 3, and 4 are experiments examining team leader reactions to speaking up, both at the time speaking up occurs (Study 2) and later, during performance evaluation (Studies 2, 3, and 4). Results provide evidence that team leaders react with irritation at the time speaking up occurs, particularly if a team member raises an audit effectiveness issue that could increase audit effort. However, team leaders reward speaking up in performance evaluations, particularly when team members speak up about issues that align with the effectiveness or efficiency focus of the team. While supervisors' performance evaluations exhibit outcome effects, supervisors also reward speaking up, regardless of outcome. Data Availability: Contact the authors.

Despite documented benefits, many Total Joint Replacement (TJR) patients find it difficult to access rehabilitation following discharge from hospital. One solution to improve access for TJR patients is telerehabilitation. This study aimed to assess the feasibility of introducing a telerehabilitation program for TJR patients. TJR patients at QEII Jubilee Hospital were invited to complete a questionnaire regarding their access, feelings towards and preferences in using technology. Seventy-five patients were recruited. Most patients had computer access (72%) and internet (69%) at home. Sixty-five percent of participants were willing to participate in telerehabilitation. A significant difference was found between older and younger patients. Watching videos on an electronic device was the preferred method for a technology-based home exercise program and phone call the preferred method of communication. Results indicate telerehabilitation in the TJR population is feasible from the perspective of access to, feelings toward, and preferences for technology.Keywords: Hip replacement, Knee replacement, Telerehabilitation, Telemedicine, Total joint replacement

SummaryBackground Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. Aim To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. Methods Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. Results A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P

Auditors must ensure that their audit plans budget sufficient time for key audit steps. Research has shown that insufficient audit time budgets can be detrimental to audit quality. We examine whether framing audit steps negatively (e.g., assess whether management's assumptions are not appropriate) increases time budgets—particularly for steps in which the auditor perceives that performance quality is less verifiable, and thus most at risk of being performed with low quality. First, we report the results of analyses indicating that, in practice, audit steps are predominantly framed positively, potentially resulting in smaller time budgets. We then report the results of an experiment in which 50 experienced audit managers budget time for an audit program that tests a Level-3 fair-value estimate. Prior research and Public Company Accounting Oversight Board (PCAOB) inspections indicate that this is a challenging audit area, vulnerable to allegations of low audit quality. The results support our predictions and suggest that reframing audit steps negatively would increase audit time budgets—an audit quality indicator—particularly for less-verifiable steps.

Antiretroviral therapy (ART) simplification to a single-tablet regimen can benefit HIV-1-infected, virologically suppressed, individuals on ART composed of multiple pills.We assessed long-term efficacy and safety of switching to co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) from multi-tablet ritonavir-boosted protease inhibitor (PI + RTV) plus F/TDF (TVD) regimens.STRATEGY-PI was a 96-week, phase 3b, randomized (2:1), open-label, non-inferiority study examining the efficacy, safety, and tolerability of switching to E/C/F/TDF from PI + RTV + TVD regimens in virologically suppressed individuals (HIV-1 RNA 50 copies/mL). Participants were randomized to switch to E/C/F/TDF (switch group) or to continue their PI + RTV + TVD regimens (no-switch group). Eligibility criteria included no resistance to F/TDF or history of virologic failure, and estimated creatinine clearance ≥70 mL/min.At week 96, 87% (252/290) of switch and 70% (97/139) of no-switch participants maintained HIV-1 RNA 50 copies/mL (difference: 17%, 95% CI 8.7-26.0%, p 0.001). Superiority of the switch to E/C/F/TDF vs. no-switch was due to a smaller proportion of both virologic failures (switch, 1% [3/290]; no-switch, 6% [8/139]) and discontinuations for non-virologic reasons (switch, 11% [31/290]; no-switch, 24% [33/139]). No treatment-emergent resistance was observed in switch subjects with virologic failure. Discontinuation rates from adverse events were 3% in both groups (9/293, switch; 4/140, no-switch). Switching from PI + RTV + TVD to E/C/F/TDF was associated with significant improvements in patient-reported outcomes related to gastrointestinal symptoms (nausea and bloating).E/C/F/TDF is a safe, effective long-term alternative to multi-tablet PI + RTV + TVD-based regimens in virologically suppressed, HIV-1-infected adults, and improves patient-reported gastrointestinal symptoms.

Successful treatment of HIV-associated multicentric Castleman disease (HIV+MCD) with rituximab-based approaches has dramatically improved survival and reduced the risk of human herpesvirus 8 (HHV8)-associated lymphoma. Longer term outcomes including relapse rates have not been described and are important to establish the potential role of maintenance therapy. A prospective cohort of 84 patients with biopsy-proven HIV+MCD were treated with risk-stratified rituximab-based therapy. Four patients (5%) died of refractory HIV+MCD and 80 achieved clinical remission. The median follow-up for the 80 patients was 6.9 years and their 5-year overall survival was 92% (95% confidence interval [CI], 85 to 99). Eighteen have relapsed (all histologically confirmed), including 5 with concomitant HHV8-associated lymphoma and MCD at relapse. The 5-year relapse-free survival is 82% (95% CI, 72 to 92). No clinical or laboratory findings that were present at MCD diagnosis predicted subsequent relapse, and the median time to first relapse was 30 months (maximum, 10 years). There were no significant differences in clinicopathological features at initial diagnosis and at relapse. All patients were successfully retreated at relapse with rituximab-based therapy. Only 1 patient died of relapsed MCD (at fifth relapse 9.4 years after initial diagnosis). Despite the use of rituximab, the risk of developing HHV8-associated lymphoma was significantly elevated in this cohort, with an incidence of 11.4/1000 person-years. The relatively low relapse rate and high salvage rates at relapse reduce the potential benefit of maintenance therapy; this should only be advocated in the context of a clinical trial.

Hop stunt viroid (HSVd) is an economically important pathogen that reduces growth and yield of hops. Visual symptoms of infected hop are highly dependent on cultivar. A study was conducted using six cultivars of hop to determine the impact on yield. Average dry cone yields of infected ‘Glacier’, ‘Cascade’, and ‘Willamette’ were reduced by 62, 14, and 34%, respectively, relative to noninoculated healthy plants. No significant yield reduction was observed for ‘Nugget’, ‘Columbus’, and ‘Galena’. The α-acid and β-acid contents showed a parallel pattern. Horticultural parameters of Willamette and Nugget were measured in the final year of the study. Internode length, shoot length, and side-arm length were reduced by 29, 26, and 73%, respectively, for infected Willamette bines relative to noninfected bines; no effects were observed resulting from infection of Nugget. To understand the current potential impact of HSVd, a survey was conducted to determine its distribution in central Washington. The survey revealed that 17% of hop plants tested are infected. Hop yield and hop plant longevity will be significantly affected by this level of infection. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

BACKGROUND: Both hyperfibrinolysis and fibrinolysis shutdown can occur after severe trauma. The subgroup of trauma patients with fibrinolysis shut- down resistant to tissue plasminogen activator (t-PA)-mediated fibrinolysis have increased mortality. Fibrin polymerization and structure may influence fibrinolysis subgroups in trauma, but fibrin architecture has not been characterized in acutely injured subjects. We hypothesized that fibrin polymerization measured in situ will correlate with fibrinolysis subgroups. METHODS: Blood samples were collected from trauma patients and noninjured controls. We selected samples across a range of fibrinolysis phenotypes (shutdown, physiologic, hyperfibrinolysis) and t-PA sensitivities (sensitive, physiologic, resistant) determined by thrombelastography. Plasma clots were created in situ with fluorescent fibrinogen and imaged using confocal microscopy for analysis of clot architecture in three dimensions. For each clot, we quantified the fiber resolvability, a metric of fiber distinctness or clarity, by mapping the variance of fluores- cence intensity relative to background fluorescence. We also determined clot porosity by measuring the size and distribution of the gaps between fibrin fibers in three-dimensional space. We compared these measures across fibrinolysis subgroups. RESULTS: Fiber resolvability was significantly lower in all trauma subgroups compared with controls (n = 35 and 5, respectively; p < 0.05). We observed markedly different patterns of fibrin architecture among trauma patients stratified by fibrinolysis subgroup. Subjects with t-PA–resistant fibrinolysis shutdown exhibited abnormal, densely packed fibrin clots nearly devoid of pores. Individuals with t-PA–hypersensitive fibrinolysis shutdown had highly irregular clots with pores as large as 2500 μm3 to 20,000 μm3, versus 78 μm3 to 1250 μm3 in noninjured controls. CONCLUSION: Fiber resolvability was significantly lower in trauma patients than controls, and subgroups of fibrinolysis differ in the porosity of the fibrin clot structure. The dense fibrin network in the t-PA–resistant group may prevent access to plasmin, suggesting a mechanism for thrombotic morbidity after injury.

The Resources Planning Act (RPA) Assessment uses a combination of land use and land cover data to evaluate trends in the United States land base and project future changes. This publication describes how the RPA Assessment uses the National Resources Inventory, National Land Cover Database, and Forest Inventory and Analysis to support analyses of forest trends. The authors compare and contrast differences in definitions and approaches of these three major data sources and document the recent status and trends of land use and land cover area according to these sources. While the general definitions of land uses and land covers are superficially similar among these sources, understanding the conceptual and technical differences between them is necessary to evaluate and compare trends in the U.S. land base. Some differences can be rationalized based on the sensitivity of the different databases to the underlying drivers of landscape change over time. However, the major difference is the perception of the land base in terms of its intended human use versus its current biophysical cover. The RPA Assessment will continue to use both land use and land cover data separately and in combination because each source offers both unique and complementary perspectives on land base trends.

Humans have the ability to learn and reason about a new concept from just one or a handful of examples, incorporate new information and modify existing patterns quickly. In this paper, we attempt to develop flexible and robust one-shot classifiers with such properties. First, we consider the biologically motivated Regulatory Feedback Networks (RFNs) as the solution. Second, we reformulate the recognition problem of RFNs as the minimization of the difference between the reconstruction of the internal copy of the inputs on hand and the inputs from the environment. Then generalized AB-divergence is introduced as a scalar measure of that difference. Based on the divergence, a set of Multiplicative Update Rules are formally derived. With the flexibility and robustness of generalized AB-divergence, these algorithms achieve strong results for one-shot learning and statistically significantly outperformed the most popular classifiers, Support Vector Machine (SVN) and K-Neares Neighbors(KNN) for few-shots learning in face and character recognition over LFW and Omniglot datasets.

Background: Spontaneous deep intracerebral hemorrhage (ICH) is a devastating subtype of stroke without specific treatments. It has been thought that smooth muscle cell (SMC) degeneration at the site of arteriolar wall rupture may be sufficient to cause hemorrhage. However, deep ICHs are rare in some aggressive small vessel diseases that are characterized by significant arteriolar SMC degeneration. Here we hypothesized that a second cellular defect may be required for the occurrence of ICH. Methods: We studied a genetic model of spontaneous deep ICH using Col4a1 +/G498V and Col4a1 +/G1064D mouse lines that are mutated for the α1 chain of collagen type IV. We analyzed cerebroretinal microvessels, performed genetic rescue experiments, vascular reactivity analysis, and computational modeling. We examined postmortem brain tissues from patients with sporadic deep ICH. Results: We identified in the normal cerebroretinal vasculature a novel segment between arterioles and capillaries, herein called the transitional segment (TS), which is covered by mural cells distinct from SMCs and pericytes. In Col4a1 mutant mice, this TS was hypermuscularized, with a hyperplasia of mural cells expressing more contractile proteins, whereas the upstream arteriole exhibited a loss of SMCs. TSs mechanistically showed a transient increase in proliferation of mural cells during postnatal maturation. Mutant brain microvessels, unlike mutant arteries, displayed a significant upregulation of SM genes and Notch3 target genes, and genetic reduction of Notch3 in Col4a1 +/G498V mice protected against ICH. Retina analysis showed that hypermuscularization of the TS was attenuated, but arteriolar SMC loss was unchanged in Col4a1 +/G498V , Notch3 +/− mice. Moreover, hypermuscularization of the retinal TS increased its contractility and tone and raised the intravascular pressure in the upstream feeding arteriole. We similarly found hypermuscularization of the TS and focal arteriolar SMC loss in brain tissues from patients with sporadic deep ICH. Conclusions: Our results suggest that hypermuscularization of the TS, through increased Notch3 activity, is involved in the occurrence of ICH in Col4a1 mutant mice, by raising the intravascular pressure in the upstream feeding arteriole and promoting its rupture at the site of SMC loss. Our human data indicate that these 2 mutually reinforcing vascular defects may represent a general mechanism of deep ICH.

Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people&rsquo, s quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. Methods: PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla&trade, ) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera&trade, ). CNS parameters including sleep, anxiety, and depressive symptoms were evaluated using patient-reported outcome measures at baseline, 4, 12, and 24 weeks after switching therapy. A median CNS score was derived from the sum of CNS toxicities of all the grades collected in the study questionnaires. Cognitive function was assessed using a computerized test battery. Results: Of 41 participants, median age was 47 years, Interquartile range (IQR) 31, 92% were male and 80% were of white ethnicity. A significant reduction in total CNS score (10 to 7) was observed at 4 weeks (p = 0.028), but not thereafter. Significant improvements in sleep and anxiety were observed 4, 12 and 24 weeks after switching therapy (p &lt, 0.05). No significant change in global cognitive scores was observed. Conclusions: Switching from efavirenz to rilpivirine based regimens in virologically suppressed PLWH without perceived CNS symptoms was well tolerated and slightly improved overall CNS symptoms.

Various lepidopteran insects are responsible for major crop losses worldwide. Although crop plant varieties developed to express Bacillus thuringiensis (Bt) proteins are effective at controlling damage from key lepidopteran pests, some insect populations have evolved to be insensitive to certain Bt proteins. Here, we report the discovery of a family of homologous proteins, two of which we have designated IPD083Aa and IPD083Cb, which are from Adiantum spp. Both proteins share no known peptide domains, sequence motifs, or signatures with other proteins. Transgenic soybean or corn plants expressing either IPD083Aa or IPD083Cb, respectively, show protection from feeding damage by several key pests under field conditions. The results from comparative studies with major Bt proteins currently deployed in transgenic crops indicate that the IPD083 proteins function by binding to different target sites. These results indicate that IPD083Aa and IPD083Cb can serve as alternatives to traditional Bt-based insect control traits with potential to counter insect resistance to Bt proteins.

Trait-based climate vulnerability assessments based on expert evaluation have emerged as a rapid tool to assess biological vulnerability when detailed correlative or mechanistic studies are not feasible. Trait-based assessments typically view vulnerability as a combination of sensitivity and exposure to climate change. However, in some locations, a substantial amount of information may exist on system productivity and environmental conditions (both current and projected), with potential disparities in the information available for data-rich and data-poor stocks. Incorporating this level of detailed information poses challenges when conducting, and communicating uncertainty from, rapid vulnerability assessments. We applied a trait-based vulnerability assessment to 36 fish and invertebrate stocks in the eastern Bering Sea (EBS), a data-rich ecosystem. In recent years, the living marine resources of the EBS and Aleutian Islands have supported fisheries worth more than US $1 billion of annual ex-vessel value. Our vulnerability assessment uses projections (to 2039) from three downscaled climate models, and graphically characterizes the variation in climate projections between climate models and between seasons. Bootstrapping was used to characterize uncertainty in specific biological traits and environmental variables, and in the scores for sensitivity, exposure, and vulnerability. The sensitivity of EBS stocks to climate change ranged from "low" to "high," but vulnerability ranged between "low" and "moderate" due to limited exposure to climate change. Comparison with more detailed studies reveals that water temperature is an important variable for projecting climate impacts on stocks such as walleye pollock (Gadus chalcogrammus), and sensitivity analyses revealed that modifying the rule for determining vulnerability increased the vulnerability scores. This study demonstrates the importance of considering several uncertainties (e.g., climate projections, biological, and model structure) when conducting climate vulnerability assessments, and can be extended in future research to consider the vulnerability of user groups dependent on these stocks.

Background: Chronic Disease Management (CDM) plans are usually administered by general practitioners (GPs) to assist those with a chronic medical condition, such as stroke, and provide better management of risk factors. Despite the prevalent use of CDM plans, its comprehensiveness and the fact that there is a government commitment to fund it, there is limited evidence of its effectiveness in Australian survivors of stroke. We aimed to assess the effectiveness of CDM plans on preventing the recurrence of CVD-related serious adverse events. Methods: Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Poisson regression models were used to determine the incidence rate ratio (IRRs) of increasing exposure to being on a CDM plan over 3 years, while adjusting for confounding factors. We used the total count of CVD-related events and deaths within 3 years after stroke/TIA, based on either hospital discharge codes or adjudication by two independent stroke specialists. Results: Five hundred and sixty-three patients were included (median age 70; 36% female). There were 305 CVD-related events over the three years (mean 0.54), in which a third (104) were adjudicated and two-thirds (201) were derived from hospital discharge codes alone. Nearly a quarter (27%) did not take up a CDM plan over the three years, a third (33%) were on plans for less than 1.5 years and 40% were on plans from 1.5 years to 3 years. The factors most strongly associated with decreased incidence of CVD-related events were duration on a CDM plan (Adjusted IRR (aIRR) 0.85, 95% confidence interval (95%CI) 0.77-0.93; p Conclusion: Being on a CDM plan for a longer duration appeared to reduce the occurrence of CVD-related events within 3 years after stroke, potentially via more closely controlled risk factors. Patients should be encouraged to return for regular reviews of their CDM plans to enhance secondary prevention strategies, and maintain a better quality of life.