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Histones organize DNA within cellular nuclei, but they can be released from damaged cells. In peripheral tissues extracellular histones act as damage-associated molecular patterns (DAMPs) inducing pro-inflammatory activation of immune cells. Limited studies have considered DAMP-like activity of histones in the central nervous system (CNS); therefore, we studied the effects of extracellular histones on microglia, the CNS immunocytes, and on neuronal cells. Both the linker histone H1 and the core histone H3 induced pro-inflammatory activation of microglia-like cells by upregulating their secretion of NO and cytokines, including interferon-γ-inducible protein 10 (IP-10) and tumor necrosis factor-α (TNF). The selective inhibitors MMG-11 and TAK-242 were used to demonstrate involvement of toll-like receptors (TLR) 2 and 4, respectively, in H1-induced NO secretion by BV-2 microglia. H1, but not H3, downregulated the phagocytic activity of BV-2 microglia. H1 was also directly toxic to all neuronal cell types studied. We conclude that H1, and to a lesser extent H3, when released extracellularly, have the potential to act as a CNS DAMPs. Inhibition of the DAMP-like effects of extracellular histones on microglia and their neurotoxic activity represents a potential strategy for combating neurodegenerative diseases that are characterized by the adverse activation of microglia and neuronal death. • Extracellular histones were hypothesized to be DAMPs of the central nervous system. • H1 or H3 histones were applied directly to cultured microglial and neuronal cells. • Pro-inflammatory activation of murine and human microglia-like cells was observed. • H1-induced NO secretion by BV-2 microglia was reduced by TLR4 and TLR2 inhibitors. • H1, but not H3, was directly toxic to murine primary neurons and neuronal cell lines. [ABSTRACT FROM AUTHOR]

Post-event rumination, the extent to which one engages in persistent, detailed, and negative thinking following social situations, serves as a risk process in the pathophysiology of social anxiety. Although a substantial body of research has assessed post-event rumination and social anxiety, this literature has produced inconsistent results. We conducted a systematic review and meta-analysis to examine whether the magnitude of the association between post-event rumination and social anxiety varied as a function of questionnaire and/or task utilized. We included all studies reporting a correlation between post-event rumination and social anxiety symptomatology. Fisher's z correlation coefficients were calculated through random-effect meta-analyses. Results indicated a moderate association between post-event rumination and social anxiety symptomatology (r = 0.45, p < 0.001, 95%CI [0.40–0.50]). Subgroup meta-analyses indicated that the type of questionnaire used to assess post-event rumination (Q = 44.36, df = 3, p < 0.001) and social anxiety (Q = 26.44, df = 8, p < 0.001), as well as the task conducted prior to assessing post-event rumination (Q = 14.31, df = 2, p < 0.001), influenced the effect size. This study demonstrates a moderate relation between post-event rumination and social anxiety across the anxiety spectrum, illustrating the importance of treatments specifically targeting post-event rumination. Moreover, we highlight the importance of taking care when designing studies to explore relations between post-event rumination and social anxiety. • Greater post-event rumination is associated with greater social anxiety. • Across 35 studies, the meta-analytic effect size of this relation is moderate. • The magnitude of this effect size depends on the questionnaires and tasks used. [ABSTRACT FROM AUTHOR]

To examine the emotional communication that takes place between patients and health care providers during surveillance cystoscopy for non-muscle invasive bladder cancer (NMIBC). Participants were 57 patients with a diagnosis of NMIBC attending for surveillance cystoscopy and 10 health care professionals (HCPs). Cystoscopy procedures were audio-recorded and transcribed verbatim. Two approaches to analysis of transcriptions were undertaken: (1) a template analysis and (2) Verona Coding Definitions of Emotional Sequences. Communication during cystoscopy generally comprised of "social/small talk," "results of the cystoscopy," and "providing instructions to the patient." Emotional talk was present in 41/57 consultations, with 129 emotional cues and concerns expressed by patients. Typically patients used hints to their emotions rather than stating explicit concerns. The majority (86%) of HCPs responses to the patient did not explicitly mention the patient's emotional concern or cue. Urology trainees were less likely than other HCPs to provide space for patients to explore their emotional concerns (t = −1.78, P <.05). Emotional communication was expressed by the majority of patients during cystoscopy. While all HCPs responded to patients' emotional communication, there were a number of missed opportunities to "pick-up" on patients' emotional cues and improve communication. Urologists need to be aware of the nuances of patients' emotional communication. Learning to identify and respond appropriately to emotional cues may improve communication with patients. [ABSTRACT FROM AUTHOR]

Long-acting reversible contraceptives (LARCs) have high rates of safety, satisfaction, and continuation in adolescents and young adults (AYAs). Despite this, utilization of these methods by AYAs is low. The purpose of this study was to evaluate the negative personal perceptions or beliefs about birth control and LARCs and their association with contraceptive use in AYAs. We surveyed young people (14-24 years old) seeking care at a Title X-supported adolescent reproductive and sexual health clinic to assess negative perceptions of birth control methods, with an emphasis on LARCs. We used appropriate bivariate statistics to compare those endorsing 3 or fewer negative perceptions with those who had more than 3 and logistic regression to identify predictors of contraceptive choice. We recruited 345 participants; 337 (97.7%) completed the survey. Among respondents, the median age was 20 (range 14-24) years, and 7.04% of participants had ever been pregnant. The most commonly held negative perceptions were fear of device migration or breakage causing adverse health effects and concern about effect on future fertility. The number of negative perceptions endorsed did not differ significantly by age. However, a greater number of negative perceptions and younger age were clinical predictors of LARC nonuse. AYAs have negative perceptions about LARCs that are often inaccurate and may limit contraceptive acceptability and perceived options. Engaged and respectful dialogue with AYAs about their concerns and fears is essential to provide accurate and patient-centered contraceptive counseling and to ensure that young people can make informed contraceptive choices. [ABSTRACT FROM AUTHOR]

Achilles tendinopathy is the most prevalent lower limb tendinopathy, yet it remains poorly understood, with mismatches between observed structure and reported function. Recent studies have hypothesised that Achilles tendon (AT) healthy function is associated with variable deformation across the tendon width during use, focusing on quantifying sub-tendon deformation. Here, the aim of this work was to synthesise recent advances exploring human free AT tissue-level deformation during use. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, Embase, Scopus and Web of Science were systematically searched. Study quality and risk of bias were assessed. Thirteen articles were retained, yielding data on free AT deformation patterns. Seven were categorised as high-quality and six as medium-quality studies. Evidence consistently reports that healthy and young tendons deform non-uniformly, with the deeper layer displacing 18%–80% more than the superficial layer. Non-uniformity decreased by 12%–85% with increasing age and by 42%–91% in the presence of injury. There is limited evidence of large effect that AT deformation patterns during dynamic loading are non-uniform and may act as a biomarker of tendon health, risk of injury and rehabilitation impact. Better considered participant recruitment and improved measurement procedures would particularly improve study quality, to explore links between tendon structure, function, aging and disease in distinct populations. [ABSTRACT FROM AUTHOR]

Individuals with schizophrenia spectrum disorders (SSD) and a history of experiencing auditory verbal hallucinations (AVH) exhibit poor pitch discrimination relative to those with an SSD but no AVH history. The present study extended this research, asking if a lifetime history, and the current presence, of AVH exacerbated the pitch discrimination challenges that are seen in SSD. Participants completed a pitch discrimination task, where the tones presented differed in pitch by either 2 %, 5 %, 10 %, 25 % or 50 %. Pitch discrimination accuracy, sensitivity, reaction time (RT) and intra-individual RT variability (IIV) were examined in individuals with SSD and AVHs (AVH+; n = 46), or without AVHs (AVH-; n = 31), and healthy controls (HC; n = 131). Secondary analyses split the AVH+ group into state (i.e., actively experiencing AVH; n = 32) and trait hallucinators (i.e., a history of, but not actively experiencing, AVH; n = 16). Relative to HC, significantly poorer accuracy and sensitivity was detected in individuals with SSD at 2 % and 5 % pitch deviants, and in hallucinators at 10 %; however, no significant differences in accuracy, sensitivity, RT nor IIV were found between AVH+ and AVH- groups. No differences between state and trait hallucinators were observed. A general SSD deficit drove the current findings. The findings may inform future research into the auditory processing capabilities of AVH+ individuals. [ABSTRACT FROM AUTHOR]

To address the antimicrobial resistance (AMR) crisis, governments around the world have created action plans to optimize antimicrobial use (AMU). These plans include antimicrobial stewardship (AMS) that encompasses educational programs for healthcare workers. We discuss these programs in sub-Saharan Africa, including the opportunities and challenges arising from a highly constrained healthcare environment. [ABSTRACT FROM AUTHOR]

Owing to increase in cost and low availability of Li source causes the high rate of the energy storage devices. By focusing on these issues, the cost effective and high performed electrode is needed for energy storage application. Na based electrodes can replace the Li ion batteries because of the availability of Na is higher than the Li. The cost of the energy storage devices can be reduced by using Na instead of Li. Many other electrodes are reported based on Na ion batteries. Since in this present work we prepared O3–NaFeO 2 (NIO) high performance electrode prepared by two step hydrothermal assisted solid-state method. But the battery performance of NaFeO2 is suffers from capacity decay during long term cycling. For these issues naturally derived sucrose from the sugarcane is prepared which increase the electrochemical performance of Ac carbon coated NaFeO 2 (AC Coated NIO). The AC Coated NIO electrode delivers the capacity of about 131 mAh g−1 at 80 mA g−1. The retention capacity of material is about 92% after 100 cycles. Such electrochemical action of the current electrode can show the way to cost effective and highly performed Na ion electrode development for Energy storage devices. [ABSTRACT FROM AUTHOR]

Key challenges for Indonesia to 2050 are to reduce its dependency on fossil-based fuels and to decarbonize its energy system. This article adopts a systems approach to investigate future pathways, positing a shift from oil combustion to electricity to energize cooking stoves and vehicles. Today, electricity is predominantly generated using gas and coal. The cost-competitiveness of renewables is central to any sectoral adjustment in the nation's total primary energy supply (TPES). To study variables within the energy system, causal loop diagrams (CLDs) are constructed acknowledging three underlying elements: constraints (the energy trilemma); resource availability, oriented to physical elements and human resources (stakeholders); and the mode of regulation. Indonesia's energy market is characterized by state enterprise and price subsidies to retail consumers. We analyze the capability of private companies to drive competition among providers of renewable energy and facilitate more competitive pricing. Our results suggest that, irrespective of the composition of the TPES over the next 30 years, fossil sources will remain significant, necessitating carbon capture storage (CCS) technology as a complement to renewable energy promotion. • Fossil energy will remain dominant in the Indonesian economy in 2050. • Renewables could, however, substitute for gas and coal, meeting an expanded demand for electricity. • A market-led system could be required to accelerate acceptance of renewables. • An emerging need for carbon capture and storage to cope with emissions from fossil-based power plant and industry. [ABSTRACT FROM AUTHOR]

I remember the magic of looking through a kaleidoscope as a little girl. Brilliant, vibrant colors coming together to make symmetrical shapes that seemed as precise as they were chaotic. Each look through the lens offered something new and spectacular, different than the intricate images seen before. With a little shake and turning of a tube and the sound of colored beads, pebbles, or small pieces of glass swirling together, mirrors connect with the light in just a way to produce the beauty that we see. Who would have thought that such a small disruption leading to the destruction of a pattern could make room for the same materials to come together again to form something fantastic, though different? Each turn or shake of a kaleidoscope could represent life changes or new perspectives that require some level of deconstruction before evolving into magnificence. Or you can simply be a kid who likes pretty pictures and wild shapes, experiencing joy and the spirit of adventure with each look. Whatever your experience, interpretation, or developmental stage, kaleidoscopes allow us to appreciate wonder, creativity, and the power of play, all rolled into one mercurial lens. [ABSTRACT FROM AUTHOR]

One of the most important jobs in elementary school can be distilled down to 2 words: line leader. This is the mighty carrot to mobilize ordinarily sluggish children through their morning routine, as they look forward to standing proudly at the front of their classroom line. I have witnessed this phenomenon myself, as my first-grade son was chosen to be the glorious line leader of room 15. He moved with a sense of urgency in the morning to pack his backpack, fill his water bottle, and put on his shoes and socks, all with zero parental prompting. After I dropped him off, I secretly watched through the chain-link fence as he skipped over to his class with his head held high to claim his hard-earned position as the Tuesday line leader. The look of pride on his face was undeniable. This leadership position truly meant something to him, giving him a sense of purpose. As he marched his class to the same classroom door that they walk through every day, it was clear that the kid walking through the door had a little more shine than he had the day before. [ABSTRACT FROM AUTHOR]

Astrocytes are the main support cells of the central nervous system. They also participate in neuroimmune reactions. In response to pathological and immune stimuli, astrocytes transform to reactive states characterized by increased release of inflammatory mediators. Some of these molecules are neuroprotective and inflammation resolving while others, including reactive oxygen species (ROS), nitric oxide (NO), matrix metalloproteinase (MMP)− 9, L -glutamate, and tumor necrosis factor α (TNF), are well-established toxins known to cause damage to surrounding cells and tissues. We hypothesized that similar to microglia, the brain immune cells, reactive astrocytes can release a broader set of diverse molecules that are potentially neurotoxic. A literature search was conducted to identify such molecules using the following two criteria: 1) evidence of their expression and secretion by astrocytes and 2) direct neurotoxic action. This review describes 14 structurally diverse molecules as less-established astrocyte neurotoxins, including C-X-C motif chemokine ligand (CXCL)10, CXCL12/CXCL12(5−67), FS-7-associated surface antigen ligand (FasL), macrophage inflammatory protein (MIP)− 2α, TNF-related apoptosis inducing ligand (TRAIL), pro-nerve growth factor (proNGF), pro-brain-derived neurotrophic factor (proBDNF), chondroitin sulfate proteoglycans (CSPGs), cathepsin (Cat)B, group IIA secretory phospholipase A 2 (sPLA 2 -IIA), amyloid beta peptides (Aβ), high mobility group box (HMGB)1, ceramides, and lipocalin (LCN)2. For some of these molecules, further studies are required to establish either their direct neurotoxic effects or the full spectrum of stimuli that induce their release by astrocytes. Only limited studies with human-derived astrocytes and neurons are available for most of these potential neurotoxins, which is a knowledge gap that should be addressed in the future. We also summarize available evidence of the role these molecules play in select neuropathologies where reactive astrocytes are a key feature. A comprehensive understanding of the full spectrum of neurotoxins released by reactive astrocytes is key to understanding neuroinflammatory diseases characterized by the adverse activation of these cells and may guide the development of novel treatment strategies. • Astrocytes support neurons and also participate in neuroimmune reactions. • Astrocytes secrete neurotrophins and toxins essential to their diverse functions. • Fourteen structurally diverse, less-known astrocyte neurotoxins are identified. • Release of these molecules by astrocytes and their neurotoxic effects are reviewed. • This research can identify astrocyte-specific targets in neuroinflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Emergency department (ED) crowding and hallway care has been a serious problem for the past three decades in the United States and abroad. Myriad articles highlighting this problem and proposing solutions have had little impact on its progression.Objectives: To discuss reasons for ED crowding leading to hallway care, the impact of the coronavirus disease (COVID-19) pandemic, potential solutions, and why little has changed despite widespread awareness.Discussion: ED crowding has been a public health issue for the past three decades, leading to patient care and boarding of admitted patients in ED hallways with limited resources. This care is often substandard and precarious. The COVID-19 pandemic placed further strain on the ED safety net, especially in certain urban areas. Despite recognition of the problem, publication of studies, and proposals offering many solutions, this problem continues to worsen. Corporate and hospital leadership must be made aware of the financial and legal ramifications for failure to address potential solutions, such as inpatient hallway boarding, provision of flexible expansion care areas, smoothing of elective admissions/surgeries, and efficient inpatient discharge flow. State and federal legislation may also be required to motivate this process.Conclusions: ED crowding and hallway care will continue to worsen unless hospital leadership is willing to listen to ED staff concerns and address the problem on all levels of the hospital using previously proposed solutions. Emergency physicians should not fear termination for discussing this issue and its potential for poor clinical outcomes and ED staff morale. [ABSTRACT FROM AUTHOR]

Controversy has existed as to whether monensin will provide equal or differential benefits in a higher-energy, lower-roughage close-up diet versus a higher-roughage, lower-energy diet. Our objective was to determine the rumen effects of a controlled-energy, high-fiber diet balanced to meet but not greatly exceed energy requirements during the dry period or a traditional 2-group approach of higher-energy close-up diet. The effects of added monensin in each diet type were determined. Multiparous Holstein cows (n = 17) were fitted surgically with ruminal cannulas. During the first 4 wk of the dry period, all cows were fed a controlled-energy, high-fiber diet (CE) as a total mixed ration for ad libitum intake. During the last 3 wk before calving, half of the cows were switched to a higher-energy, close-up diet until calving (CU), whereas the other half continued to receive the CE diet. Within each dietary group, half of the cows received monensin (MON) supplementation in the diet (24.2 g/t of total dry matter) and half did not (CON). After calving, all cows received the same lactation diet containing monensin (15.4 g/t of dietary dry matter). At 14 d prepartum, dry matter intake was not different across treatments. The weight of rumen contents was greater for cows fed CE. Rumen liquid dilution rate, solids passage rate, pH, total volatile fatty acid (VFA) concentrations, molar proportions of acetate and propionate, and papillae length did not differ among diets. Butyrate percentage tended to be greater for cows fed CE. Postpartum, dry matter intake, mass of rumen contents, solids passage rate, pH, total VFA concentration, molar percentages of propionate and butyrate, and papillae length did not differ among treatments. Liquid dilution rate (16.6, 10.7, 16.0, and 18.2%/h for CE + CON, CE + MON, CU + CON, and CU + MON, respectively) was affected by a diet × monensin interaction. Cows on the CE + CON diet had a greater ruminal proportion of acetate than did cows fed CU + CON, whereas cows fed monensin on either diet were intermediate (diet × monensin interaction). Addition of MON to the CU diet decreased the proportion of propionate (diet × monensin interaction). Cows fed CE had greater mass of rumen contents before parturtition but the high inclusion of wheat straw in the CE diet did not negatively affect rumen papillae length. Monensin inclusion differentially affected liquid passage rate and VFA concentrations. [ABSTRACT FROM AUTHOR]

The aim of our study is to document our cases of choroidal melanoma treated with low dose rate (LDR) brachytherapy and to correlate the dosimetry and radiobiology with clinical effects and oncologic outcomes. Data from 157 patients treated from 2014 to 2018 with LDR brachytherapy were used for this investigation. Treatments used a collaborative ocular melanoma study eye plaque and Iodine-125 radioactive seeds. The seeds activities were chosen to deliver 85 Gy to the tumor apex or to a prescription point (if the apex < 5 mm). The plaque sizes used were 10, 12, 14, 16, 18, 20, and 22 mm including notched or deep notched. The plaques were modeled in Varian BrachyVision version 11.6 (Varian Medical Systems) with seed coordinates from the AAPM Task Group 129. The Task Group 43 from AAPM was used for brachytherapy dose planning. Dose data were extracted for the apex, prescription point, sclera, retina opposite to the implant, lens, macula, and optic disc. The radiobiological dosimetry were calculated using appropriate α/β ratios found in the literature and then correlated to clinical side effects. Average biologically effective dose for associated organs at risk were calculated in cases where toxicity occurred. These included: radiation cataract (70.66 Gy), disc atrophy (475.49 Gy), foveal atrophy (263.07 Gy), radiation papillopathy (373.45 Gy), radiation maculopathy (213.62 Gy), vitreous hemorrhage (1437.68 Gy), vascular occlusion (1080.93 Gy), nonproliferative retinopathy (1066.89 Gy), proliferative retinopathy (1590.71 Gy), exudative retinal detachment (1364.32 Gy), and rhegmatogenous retinal detachment (2265.54 Gy). Average biologically effective dose was higher in patients who developed radiation induced long term side effects than in the whole patient population except for radiation maculopathy. In spite of the small patient population and short-term follow-up, it is of interest to correlate the radiation induced effects and create a guideline for the improvement of the treatment of patients treated with LDR brachytherapy. [ABSTRACT FROM AUTHOR]

Background: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown.Methods: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery.Results: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001).Conclusions: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated.Clinical Trial Registration: NCT04978285 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

• A multipass, high throughput structured catalyst for intensified plant operation. • Continuous H 2 generation using additively manufactured Catalytic Static Mixer. • A custom-built dehydrogenation reactor uses Catalytic Static Mixer as insert. • Detailed thermal profiles of the reactor using electrical heating are collected. • System pressure increases with increasing hydrogen production. Herein we describe a multipass Catalytic Static Mixer (CSM) for implementation in on-demand hydrogen generation. The insert is a 3D printed metal scaffold with a catalyst coating containing a multitude of channels and a hollow core for a heater rod. This next generation of CSMs offers higher throughput and increased residence times for applications involving liquid-gas or gas only flow. We have implemented this CSM as an insert in a continuous flow tubular reactor for the dehydrogenation of Liquid Organic Hydrogen Carriers (LOHCs). The catalyst coating is comprised of 5 wt.% Pt/Al 2 O 3 and is used for the dehydrogenation of methylcyclohexane (MCH) to generate hydrogen gas as the model system. This experimental study investigates the thermal profiles of the reactor and validates the potential of the CSM technology in hydrogen generation from LOHCs. [Display omitted] [ABSTRACT FROM AUTHOR]

As child and adolescent psychiatrists, it is our job to identify factors that influence the behaviors seen in front of us. Often the question is asked whether these factors are primarily due to nature or nurture: Is someone born a "bad kid," or are there environmental exposures that lead to less than ideal behaviors? Factors such as racism, poverty, bullying, social isolation, and even where we grow up could play a part in the behaviors seen. This is one of the most rewarding, but at times can be one of the most frustrating, parts of our job as child and adolescent psychiatrists. Hopefully we can explore the factors influencing behaviors seen by the children we work with, highlighting the good in them and the situations that have led to the concerns seen. At the same time, we can become frustrated knowing that some of these factors are difficult for us to change as an individual child and adolescent psychiatrist, such as racism, poverty, inequalities in education, or family support. Bearing witness to these societal issues and their impact on our patients hopefully sparks advocacy efforts toward larger system changes. [ABSTRACT FROM AUTHOR]

To assess the potential of apparent diffusion coefficient (ADC) values derived from diffusion weighted (DW) MRI preoperatively to predict the predominant histologic component among biphasic pleural mesothelioma (PM) tumors. ADC maps were generated from DW MRI scans. Histology and predominant component of biphasic PM were confirmed following surgical resection. Statistical analyses were done with R (R Foundation for Statistical Computing, Vienna, Austria). Average ADC values corresponding to epithelioid- and sarcomatoid-predominant tumors were compared. ADC thresholding was accomplished by recursive partitioning and confirmed with ROC analysis. Eighty-four patients with biphasic PM's, 69 (82 %) epithelioid-predominant (BE) and 15(18 %) sarcomatoid-predominant (BS) tumors were evaluated. Thirty-eight (45 %) patients underwent extrapleural pneumonectomy (EPP), 39 (46 %) had extended pleural decortication (ePDC) and 7 (8 %) had pleural decortication (PDC). ADC values ranged between 0.696 x 10-3 to 1.921 x 10-3 mm2/s. BE tumors demonstrated significantly higher ADC values than BS tumors (p = 0.026). ADC values above 0.94 x 10-3 mm2/s were associated with a significant increase of relative risk of being in group BE over group BS (relative risk: 1.47, 95 %CI: 1.05–2.06, p = 0.027) Average ADC values of BE tumors were higher than BS tumors and the two groups can be separated by a cut off value of 0.94 X 10-3 mm2/s. [ABSTRACT FROM AUTHOR]

Protein–protein interactions (PPIs) play a critical role in cellular signaling and represent interesting targets for therapeutic intervention. 14-3-3 proteins integrate many signaling targets via PPIs and are frequently implicated in disease, making them intriguing drug targets. Here, we review the recent advances in the 14-3-3 field. It will discuss the roles 14-3-3 proteins play within the cell, elucidation of their expansive interactome, and the complex mechanisms that underpin their function. In addition, the review will discuss significant advances in the development of molecular glues that target 14-3-3 PPIs. In particular, it will focus on novel drug discovery and development methodologies that have delivered selective, potent, and drug-like molecules that could open new avenues for the development of precision molecular tools and medicines. An illustration summarizing the concepts and discussion points covered in this review. [Display omitted] [ABSTRACT FROM AUTHOR]

Rupture and repair are key ingredients to connection. When ruptures in relationships occur, which they will, it is important to revisit the situation to work on restoring safety, regulation, attunement, and understanding. Through engaging in this process and providing consistent secure base and safe haven supports, conflicts have the opportunity to heal. Developmentally, the practice of rupture and repair begins during infancy and early childhood, laying the foundation for secure attachment. What happens when ruptures repeatedly occur without repair? How does this impact self-esteem and the narratives children create about themselves as they grow? As you can imagine, repeated rupture without repair can lead to mistrust, cognitive distortions, resentment, and emotional stunting. As child and adolescent psychiatrists, we can help families understand that relationships, like people, can bend without breaking—and that a healthy serving of humble pie can be just what the doctor ordered. [ABSTRACT FROM AUTHOR]

Cement is an essential construction material due to its ability to flow before later setting, however the rheological properties must be tightly controlled. Despite this, much understanding remains empirical. Using a combination of continuous and oscillatory shear flow, we compare fresh Portland cement suspensions to previous measurements on model non-Brownian suspensions to gain a micro-physical understanding. Comparing steady and small-amplitude oscillatory shear, we reveal two distinct jamming concentrations, ϕ μ and ϕ rcp , where the respective yield stresses diverge. As in model suspensions, the steady-shear jamming point is notably below the oscillatory jamming point, ϕ μ < ϕ rcp , suggesting that it is tied to frictional particle contacts. These results indicate that recently established models for the rheology of frictional, adhesive non-Brownian suspensions can be applied to fresh cement pastes, offering a new framework to understand the role of additives and fillers. Such micro-physical understanding can guide formulation changes to improve performance and reduce environmental impact. [Display omitted] • The yield stress of fresh cement depends strongly on protocol. • The steady flow yield stress diverges before the oscillatory yield stress. • Two yield-stress branches reveal role of inter-particle contact friction. • Start-up shear flow explicitly links two yielding events. [ABSTRACT FROM AUTHOR]

Compassion is critical to the provision of high-quality healthcare and is foregrounded internationally as an issue of contemporary concern. Paid care experience prior to nurse training has been suggested as a potential means of improving compassion, which has been characterised by the values and behaviours of care, compassion, competence, communication, courage, and commitment. There is however a dearth of evidence to support the effectiveness of prior care experience as a means of improving compassion in nursing. To explore the impact of paid prior care experience on the values and behaviours of pre-registration nursing students indicated as characterising compassionate care. Longitudinal mixed methods design employing a modified concurrent triangulation strategy, comprising two work packages. Work package 1 was qualitative, and work package 2 adopted a concurrent embedded strategy with a dominant quantitative component. Research is reported in accordance with the Good Reporting of a Mixed Methods Study framework. Three United Kingdom universities. Pre-registration nursing students attending one of three universities, and individuals who had previously participated in a Health Education England paid prior care experience pilot. Participant numbers at time point 1 were questionnaires n = 220, telephone interviews n = 10, and focus groups n = 8. Work package 1 consisted of longitudinal semi-structured telephone interviews. Work package 2 comprised validated online questionnaires measuring emotional intelligence, compassion satisfaction and fatigue, resilience, psychological empowerment, and career commitment (as proxies of compassionate values and behaviours), and focus groups. Qualitative data were thematically analysed. Quantitative data were analysed via Analysis of Variance in SPSS v 26. Qualitative findings suggest that prior care experience has both positive and negative effects on students' compassionate values and behaviours, however positive effects do not extend to qualification. No statistically significant differences were found in any of the quantitative outcome measures between participants with and without paid prior care experience. A statistically significant increase in compassion fatigue was identified in both groups of participants post-qualification. Paid prior care experience did not prevent participants from experiencing reality shock on becoming a student or on qualification. There is insufficient evidence of longitudinal beneficial impact to recommend paid prior care experience as an effective intervention to foster nursing students' compassionate values and behaviours. These findings do not support mandating a period of paid care experience as a prerequisite for entry into nurse education. N/A. Tweetable abstract Insufficient evidence of longitudinal beneficial impact to recommend prior care experience as an effective intervention to foster nursing student compassion @PriorCareExp @Sarah_F_R [ABSTRACT FROM AUTHOR]

As child psychiatrists, it is our job to ask questions, and many of us would say we are really good at it. We work with our patients to open up about their experiences, discussing fear, sadness, hope, and joy. By modeling this ability to open up in the office, we help guide children and adolescents through using other skills rather than avoidance. Although avoidance has its place at times, we help show our patients the connection between anxiety and avoidance. This necessity to embrace and challenge fears can be a difficult skill for our patients and also their families. Children bring forward questions that parents may want to avoid, fearing the answer might be more difficult for the child than the rejection of having the question avoided all together. As someone who works with children with chronic illnesses, this avoidance of the question can in fact increase the fear and anxiety of the child or adolescent. When talking to children, often they will express a greater fear than the reality of the situation because they determine that if their parent is avoiding the question, it must be really bad. This same struggle with avoidance can be true for us as child psychiatrists as well. The necessity to take on roles of leadership or run a team often presents itself, but excuses can come up to help us avoid these roles. We might say we are not properly trained, we did not go into medicine to do those responsibilities, or we are too busy. By avoiding these responsibilities, we are setting ourselves up for more frustration. As teams struggle, we have to follow the lead of others without the same clinical knowledge, which may result in additional errors. We must remember to practice what we preach and to identify the cost of avoidance. [ABSTRACT FROM AUTHOR]

Objective: Recognition of out-of-hospital cardiac arrest (OHCA) during 9-1-1 calls is critically important, but little is known about how laypersons and emergency medical dispatchers (EMDs) communicate. We sought to describe 9-1-1 calls for OHCA.Methods: We performed a mixed-methods, retrospective analysis of 9-1-1 calls for OHCA victims in a large urban emergency medical services (EMS) system using a random sampling of cases containing the term "cardiopulmonary resuscitation" (CPR) in the EMS electronic report. A constant comparison qualitative approach with four independent reviewers continued until thematic saturation was achieved. Quantitative analysis employed computational linguistics. Callers' emotional states were rated using the emotional content and cooperation score (ECCS).Results: Thematic saturation was achieved after 46 calls. Three "OHCA recognition" themes emerged [ 1) disparate OHCA terms used, 2) OHCA mimics create challenges, 3) EMD questions influence recognition]. Three "CPR facilitation" themes emerged [ 1) directive language may facilitate CPR, 2) specific instructions assist CPR, 3) caller's emotions affect CPR initiation]. Callers were generally "anxious but cooperative." Callers saying "pulse" was associated with OHCA recognition.Conclusion: Communication characteristics appear to influence OHCA recognition and CPR facilitation.Practice Implications: Dispatch protocols that acknowledge characteristics of callers' communication may improve OHCA recognition and CPR facilitation. [ABSTRACT FROM AUTHOR]

Peek-A-Boo is a beloved game played around the world, crossing language and cultural barriers alike. In addition to reinforcing the magical principle of object permanence, Peek-A-Boo generates laughter and shared joy that is contagious. While engaging with a patient diagnosed with postpartum depression, I was delighted to witness the power of this game on full display. When her 10-month-old son grew fussy as she discussed her matrescence, the patient gave me a playful look before abruptly covering her eyes with both hands. She waited a moment, then quickly uncovered her eyes while squealing " Peek-A-Boo, I see you!" I can still hear his gasp of surprise followed by a hearty, deeply committed belly laugh that echoed in the room. Why is this game so universally loved? Is it because it promotes connection, can be used as a powerful learning tool, or perhaps because it reinforces the idea that things stick around even when you can't see them? Maybe it is all of these things swirling together at once, built on a deeper principle that feeling seen and accepted without condition feels pretty darn good. Either way, I walked away from that encounter reminded of the simple truth that laughter—especially from a spirited baby—can be the best medicine. [ABSTRACT FROM AUTHOR]

• A rare and unreported mutation was discovered in I-As expressed autoimmunity prone SJL mice. • A single amino acid polymorphism alters MHC class II structural features. • CD4 T cell reactivity with I-As suggests TcR docking towards peptides' amino terminus. • Autoimmune T cells may share common features of T cell receptor recognition. In the process of structure-function studies on the MHC class II molecule expressed in autoimmunity prone SJL mice, I-As, we discovered a disparity from the reported sequence of the MHC class II beta chain. The variant is localized at a highly conserved site of the beta chain, at residue 58. Our studies revealed that this single amino acid substitution of Pro for Ala at this residue, found in I-As, changes the structure of the MHC class II molecule, as evidenced by a loss of recognition by two monoclonal antibodies, and elements of MHC class II conformational stability identified through molecular dynamics simulation. Two other rare polymorphisms in I-As involved in hydrogen bonding potential between the alpha chain and the peptide main chain are located at the same end of the MHC class II binding pocket, studied in parallel may impact the consequences of the β chain variant. Despite striking changes in MHC class II structure, CD4 T cell recognition of influenza-derived peptides was preserved. These disparate findings were reconciled by discovering, through monoclonal antibody blocking approaches, that CD4 T cell recognition by I-As restricted CD4 T cells focused more on the region of MHC class II at the peptide's amino terminus. These studies argue that the conformational variability or flexibility of the MHC class II molecule in that region of I-As select a CD4 T cell repertoire that deviates from the prototypical docking mode onto MHC class II peptide complexes. Overall, our results are consistent with the view that naturally occurring MHC class II molecules can possess polymorphisms that destabilize prototypical features of the MHC class II molecule but that can maintain T cell recognition of the MHC class II:peptide ligand via alternate docking modes. [ABSTRACT FROM AUTHOR]

Drugs and drug metabolites containing a carboxylic-acid moiety can undergo in vivo conjugation to form 1-β-O-acyl-glucuronides (1-β-O-AGs). In addition to hydrolysis, these conjugates can undergo spontaneous acyl migration, and anomerisation reactions, resulting in a range of positional isomers. Facile transacylation has been suggested as a mechanism contributing to the toxicity of acyl glucuronides, with the kinetics of these processes thought to be a factor. Previous 1H NMR spectroscopic and HPLC-MS studies have been conducted to measure the degradation rates of the 1-β-O-AGs of three nonsteroidal anti-inflammatory drugs (ibufenac, R-ibuprofen, S-ibuprofen) and a dimethyl-analogue (termed here as "bibuprofen"). These studies have also determined the relative contributions of hydrolysis and acyl migration in both buffered aqueous solution, and human plasma. Here, a detailed kinetic analysis is reported, providing the individual rate constants for the acyl migration and hydrolysis reactions observed in buffer for each of the 4 AGs, together with the overall degradation rate constants of the parent 1-β-O-AGs. Computational modelling of the reactants and transition states of the transacylation reaction using density functional theory indicated differences in the activation energies that reflected the influence of both substitution and stereochemistry on the rate of transacylation/hydrolysis. [Display omitted] • 1H NMR spectroscopy was used to study NSAID 1-β-O-acyl glucuronide (AG) degradation. • Kinetic analysis gave rate constants for AG migration and AG hydrolysis/degradation constants. • In silico models gave equivalent 1-β-O-acyl glucuronide degradation rates to 1H NMR. • Activation energy rankings aligned with observed transacylation rates. • In silico models can identify structures prone to producing reactive acyl glucuronides. [ABSTRACT FROM AUTHOR]

Have you ever built a spaceship using Magna-Tiles with a 4-year-old child? If not, place this on the top of your to-do list, as there are many lessons hidden within these colorful pieces of plastic. In addition to teaching patience and cooperation, the process of building with a preschooler with big emotions and an underdeveloped prefrontal cortex offers endless opportunities to serve as both a safe haven and a secure base. As each tile is carefully (or not so carefully) placed, you are building more than just a misshapen spaceship; you are reinforcing a foundation of trust and mutual respect. In helping my own 4-year-old daughter build a unicorn-themed spaceship that resembled a tug boat, I cringed when she placed the final tile that would collapse our creative masterpiece. Much to my surprise, instead of disappointment and tears, she erupted into laughter and began the process of building all over again. She reminded me that joy can come from an experience rather than an outcome, that creativity and imagination should be sprinkled daily into the work we do, and that not every spaceship is destined to be out of this world! [ABSTRACT FROM AUTHOR]

Exposure to nature is increasingly regarded as a key part of human health, and the recognition that urban environments must provide access to green spaces for the wellbeing. The beginning of the COVID-19 pandemic in 2020 led to many governments issuing stay-at-home orders and closing parks, limiting the options of accessible green spaces for people seeking to safely socialise and cope with stress. Here, we gain a global perspective on how quickly people returned to nature (visiting parks and beaches) in comparison to necessities (accessing groceries and pharmaceuticals) and luxury activities (retail purchases and recreation) following COVID-19 lockdowns using Google Mobility data. We found that people from around the world returned to nature 76 days after peak lockdown, 28 days after people returned to necessities and 77 days before the return to luxuries. Central Asia, Europe, and Northern America returned to nature before necessities. These patterns held even after seasonally-detrending the data. We further found a strong negative correlation between the speed people pulsed back to nature and the strength of government response measures. Combined, our data support the value of nature to people and the need to consider access to green and natural space for human well-being. At the same time, the large-scale return to nature also highlighted the need to promote messages on how to minimise the impacts of human activities in these spaces. We advocate for building and protecting green spaces, combined with strong eco-education, to foster pro-environmental behaviour. • Overall, people from around the world returned to nature faster than they returned to accessing luxuries. • Many regions, particularly in Northern America and Europe, returned to nature even before necessities. • Human relationships with nature improve wellbeing, social connection, and motivate conservation action. • The importance of nature conflicts with urban development practices leading to reduced green spaces. • Access to nature should be elevated to the status of a basic human right. [ABSTRACT FROM AUTHOR]

Protein nanoparticles offer a highly tunable platform for engineering multifunctional drug delivery vehicles that can improve drug efficacy and reduce off-target effects. While many protein nanoparticles have demonstrated the ability to tolerate genetic and posttranslational modifications for drug delivery applications, this review will focus on three protein nanoparticles of increasing size. Each protein nanoparticle possesses distinct properties such as highly tunable stability, capacity for splitting or fusing subunits for modular surface decoration, and well-characterized conformational changes with impressive capacity for large protein cargos. While many of the genetic and posttranslational modifications leverage these protein nanoparticle's properties, the shared techniques highlight engineering approaches that have been generalized across many protein nanoparticle platforms. • Protein nanoparticles are capable of highly uniform multifunctionalization. • Interior modifications of protein nanoparticles can improve loading capacity. • Exterior modifications of protein nanoparticles enables cell specific targeting. • Inter-subunit modifications of protein nanoparticles can alter their behavior. [ABSTRACT FROM AUTHOR]

Steel special moment frame connections with shear-yielding haunches can be used for seismic retrofit and for new construction. In this study, shear-yielding haunch connections were investigated through experimental testing and finite element analysis. Three specimens were tested, each with a W1000 × 591 beam and W1000 × 554 column. The cyclically loaded specimens completed cycles at 0.04 rad prior to low-cycle fatigue of the haunch plates. The monotonically loaded specimen reached 0.064 rad drift. The experimental specimens had 10 to 15% post-yield stiffness, and the fuses reached the ultimate material strength prior to tearing. M-factors for the connection were determined to be 4.7 for life safety and 6.3 for collapse prevention. Finite element models were used to quantify force transfer through the connection and to investigate the retrofit-specific detail. The experiments and finite element models confirmed that a relatively simple design procedure produced acceptable designs. • Haunch connections (W1000×591 beam) with shear-yielding fuses demonstrated acceptable rotation capacity (0.04 rad). • M-factors were 4.7 for life safety and 6.3 for collapse prevention. • Finite element models confirmed the force distribution assumed in the design procedure. • Design procedures and a design example are provided. [ABSTRACT FROM AUTHOR]

The experiences of others can often be used as a motivator, caution tale, point of education, and much more. Parents describe their own experiences to help their children make the right choices, including avoiding some mistakes they might regret. We watch movies and read books about historical figures, actors, athletes, and other famous people to better understand how their experiences shaped the person they became. More recently the growth of influencer culture has led people to watch videos to make decisions based on what the person tells them of their own experience. The difficulty is that many of these experiences have been selectively crafted to fit what makes a good movie or to promote a product. [ABSTRACT FROM AUTHOR]

Targeted cancer therapy is rapidly evolving the landscape of personalized health care. Novel approaches to selectively impeding tumour growth carry significant potential to improve survival outcomes, particularly for reproductive-aged patients harbouring treatment refractory disease. Current agents fall within two classes: immunotherapy and small molecule inhibitors. These are collectively divided into the following subclasses: monoclonal antibodies; immunomodulators; adoptive cell therapy; treatment vaccines; kinase inhibitors; proteasome inhibitors; metalloproteinase and heat shock protein inhibitors; and promoters of apoptosis. The short- and long-term effects of these treatments on the female reproductive system are not well understood. As a result, clinicians are rendered unable to appropriately counsel women on downstream effects to their fertility. Data-driven consensus recommendations are desperately needed. This review aims to characterize the effect of targeted cancer therapy on the female hypothalamic–pituitary–ovary axis, direct ovarian function and conception. [ABSTRACT FROM AUTHOR]

• Microbial symbiotic interactions shape natural environments. • The functional nature of most microbial symbiotic associations is unknown. • Single-cell methods allow isolation and functional profiling of individual cells. • Atlas approaches with imaging allow the basis of interactions to be quantized. Natural environments are composed of a huge diversity of microorganisms interacting with each other to form complex functional networks. Our understanding of the operative nature of host–symbiont associations is limited because propagating such associations in a laboratory is challenging. The advent of single-cell technologies applied to, for example, animal cells and apicomplexan parasites has revolutionized our understanding of development and disease. Such cell atlas approaches generate maps of cell-specific processes and variations within cellular populations. These methods can now be combined with cellular-imaging so that interaction stage versus transcriptome state can be quantized for microbe-microbe interactions. We predict that the combination of these methods applied to the study of symbioses will transform our understanding of many ecological interactions, including those sampled directly from natural environments. [ABSTRACT FROM AUTHOR]

• External speech processing deficits are seen in individuals with AVH. • We consolidate the functional neuroimaging literature of these deficits. • Altered function and coupling of the temporal auditory regions were evident. • Some evidence of further limbic, default mode, salience and subcortical involvement. • We provide in-depth recommendations for future study designs. It has been documented that individuals who hear auditory verbal hallucinations (AVH) exhibit diminished capabilities in processing external speech. While functional neuroimaging studies have attempted to characterise the cortical regions and networks facilitating these deficits in a bid to understand AVH, considerable methodological heterogeneity has prevented a consensus being reached. The current systematic review investigated the neurobiological underpinnings of external speech processing deficits in voice-hearers in 38 studies published between January 1990 to June 2020. AVH-specific deviations in the activity and lateralisation of the temporal auditory regions were apparent when processing speech sounds, words and sentences. During active or affective listening tasks, functional connectivity changes arose within the language, limbic and default mode networks. However, poor study quality and lack of replicable results plague the field. A detailed list of recommendations has been provided to improve the quality of future research on this topic. [ABSTRACT FROM AUTHOR]

To assess outcomes of small and medium choroidal melanoma (less than 5.0 mm in height) following Iodine-125 episcleral brachytherapy. Patients with small and medium choroidal melanoma that underwent Iodine-125 brachytherapy with apical height of 1.0 mm to 5.0 mm and largest basal diameter of ≤16.0 mm were included. Data were extracted from the original dosimetry plans to determine doses to vision critical structures with the prescription point to the apical height (actual dose, ABS guidelines) and, after simulation, with the prescription point to the height of 5.0 mm (simulated dose, COMS protocol). Visual acuity (VA) outcomes with actual dose and that predicted with the simulated dose were estimated along with local recurrence, ocular survival, and survival at 5 years. A total of 339 patients with a mean age of 61.5 years with a mean follow up duration of 43.4 months were included. The mean dose reduction for lens, optic disc, and fovea was 34%, 39.4%, and 41.4%, respectively with actual dose when compared with simulated dose. The Kaplan-Meier estimations for 3 year event free rate of VA of 20/50 or better were 56% and 31% for actual dose and simulated dose, respectively. Only 3 events of local recurrence were observed (enucleated) yielding 5 year local control and ocular survival rate of 98%. Overall survival (OS) and metastasis free survival (MFS) were 95% and 87.5% at 5 years, respectively. Small and medium choroidal melanoma treated according to ABS has excellent outcomes. Brachytherapy planning using ABS guidelines as compared to COMS protocol may be associated with lower rates of radiation toxicity and vision loss. [ABSTRACT FROM AUTHOR]

Although much research has examined nursing and physician burnout, the advanced practice provider (APP) population has not yet been studied. The goal of the present study was to survey APPs in neurosurgery to determine whether greater emotional intelligence (EI) is protective against burnout. An 80-item survey was created that incorporated the Maslach Burnout Inventory Human Services Survey for Medical Personnel, the Trait Emotional Intelligence Questionnaire–short form, and original questions developed by us. The collective survey was distributed, administered, and collected using the web-based REDCap (Research Electronic Data Capture) platform. Statistical analyses were completed using a comparison between participants with and without burnout. A total of 106 neurosurgical APPs (26 men, 80 women) completed the survey, of whom, 57 (54%) reported current burnout. High average scores for personal accomplishment and global EI were inversely related to burnout (P = 0.034 and P = 0.003, respectively). In addition, the following factors were associated with burnout: inadequate support staff in the work place (P = 0.008), inadequate time off work (P < 0.001), inadequate administrative time (P = 0.009), not experiencing support from one's supervisor (P = 0.017), insufficient time for continuing medical education (P < 0.001), an inability to separate work from personal time (P < 0.001), and an inability to advance within one's professional field (P = 0.043). For neurosurgical APPs, EI is protective against burnout. Many opportunities exist at the individual and organizational level to alleviate burnout among neurosurgical APPs. Targeted strategies to improve work–life balance, EI, support systems, and opportunities for career development among neurosurgical APPs might enhance employment satisfaction and reduce burnout. [ABSTRACT FROM AUTHOR]

Objective: To interrogate the National Veterans Health Administration (VA) database to determine if beta-blocker use at time of initiation of androgen therapy deprivation (ADT) would result in improved oncological outcomes in advanced prostate cancer (PCa).Methods: All men diagnosed with high risk PCa (PSA >20) from 2000-2008 who were on ADT ≥ 6 months were identified. Patients receiving ADT concurrently with primary radiation therapy were excluded. Pharmacy data was interrogated for all beta-blockers, but then focused on the selective beta-1 blocker metoprolol. Cox proportional hazards ratios were calculated for overall survival (OS), PCa specific survival (CSS) and skeletal related events (SREs).Results: In 39,198 patients with high risk PCa on ADT, use of any beta-blocker was not associated with improvement in OS, CSS, or SREs. Further analyses focusing on metoprolol found that 10,224 (31.9%) had used metoprolol while 21,834 had no beta-blocker use. Multivariable analysis with Inverse Propensity Score Weighting, adjusted for factors including PSA, Gleason score, and duration ADT, found that utilization of metoprolol was not associated with improvement in OS (hazard ratio [HR] 0.97, P = .19), CSS (HR 0.94, P = .23) or SREs (HR 0.98, P = .79).Conclusion: In this large cohort, metoprolol use in conjunction with ADT in high risk PCa was not associated with improvement in OS, CSS, or risk of SRE. In contrast to a recent smaller clinical study, our data strongly suggests no cancer specific benefit to beta-blocker use in advanced PCa. [ABSTRACT FROM AUTHOR]

Trypanocides are a key control component of African animal trypanosomiasis (AAT) in tsetse-infested areas of sub-Saharan Africa. While farmers are dependent upon trypanocides, recent research highlights their inappropriate and ineffective use, problems with drug quality, and treatment failure. There are currently gaps in knowledge and investment in inexpensive AAT diagnostics, understanding of drug resistance, and the effective use of trypanocides in the field. Without this important knowledge it is difficult to develop best practice and policy for existing drugs or to inform development and use of new drugs. There needs to be better understanding of the drivers and behavioural practices around trypanocide use so that they can be incorporated into sustainable solutions needed for the development of effective control of AAT. Control of African animal trypanosomiasis (AAT) is hampered by limited diagnostics, inappropriate trypanocide use, poor drug quality, and drug resistance. The scope and quality of current literature on AAT incidence, control, and resistance does not allow for robust comparisons or assessment of the validity of extrapolating to other populations. A united effort is needed to address AAT at local, national, and international settings to ensure a greater chance for success. AAT control programmes must be sustainable through funding, cross-sectoral engagement, and fostering sustainable behavioural change through incentives and accountability. [ABSTRACT FROM AUTHOR]

Entrapment neuropathies affecting the sciatic nerve tract may adversely affect neural biomechanical features such as excursion and strain. There is a paucity of in vivo evidence examining the effects of forward bending upon sciatic nerve excursion and strain. The purpose of this study was to assess the reliability of ultrasound imaging in measuring sciatic nerve excursion and strain during forward bending movements. Secondary aims were to quantify sciatic nerve excursion and strain during forward bending movements and to assess the relationship between sciatic nerve excursion and movements of the hip and lumbar spine. The reliability of measuring sciatic nerve excursion was high to excellent whilst measurement of sciatic nerve strain was moderate. The amount of hip flexion, during forward bending, was a strong predictor of sciatic nerve excursion. These findings will support clinicians in the assessment and treatment of entrapment neuropathies, in addition to providing a foundation for future research. [ABSTRACT FROM AUTHOR]