Search

β-UB2C exhibits itinerant ferromagnetism below T c 75 K; whereas, UNiSi2 exhibits ferromagnetism of localized uranium moments below Tc 95 K and Kondo lattice behaviour at higher temperatures. We have found that ferromagnetism in both compounds is quenched at high pressure. In β-UB2C the Curie temperature continuously approaches zero at 2.95 GPa, where resistivity and specific heat reveal the behaviour similar to that observed in Ce-based antiferromagnets near quantum critical points. In UNiSi2 the Curie temperature decreases gradually to 25 K at 5.34 GPa. Above this pressure hysteretic phenomena appear in the temperature dependences of resistivity between 5 and 17 K, signalling a change in the magnetic order. No signature of magnetism was found above 5.5 GPa down to 1.15 K. Kondo lattice behaviour of resistivity with the enhanced residual resistivity is observed in UNiSi2 above 5.5 GPa. © Published under licence by IOP Publishing Ltd.

Abstract There are no regulations for the flyball box angulation, which ranges from 45° to 89°. As such at present, the box turn is deemed to represent the greatest injury risk to competitors. The aim of this study was to understand the influence of box angle on kinematic variables during a flyball turn, by comparing dogs turning on three different angulations of flyball box (45°, 60° and 83°) to allow for recommendations to be made regarding the most appropriate box design in terms of limiting risk of injury across the sport, to increase both wellbeing and safety for competitors. Turning on a 45° box generates significantly more flexion in the forelimbs and carpus, whereas turning on an 83° box generates greater degrees of extension in the elbow, shoulder, hock and stifle. What our 3D analysis has shown is that the relationship between box angle and the physical demands placed on the dog are complex, and related mainly to asymmetrical nature of the sport, and as such no one angle may be more or less suitable for training and competition, but the 60° seems to be a mid-ground, whereas direction of turn may be fundamental in generating the potential for injury.

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with high mortality. Low muscle mass, frailty and sarcopenia lead to functional impairment that negatively impact quality of life and survival but are not used in clinical practice. We aimed to determine the association of Fat-free mass index (FFMI) and frailty with lung function, exercise tolerance and survival in patients with IPF. In this study, 70 patients with IPF underwent assessment of body composition, lung function, 6-min walk distance (6MWD) testing, hand grip strength, quality of life (QoL) assessment by St. George’s Respiratory questionnaire (SGRQ) and frailty assessment using the SHARE-FI tool. FFMI was calculated using pectoralis muscle cross-sectional area (PM-CSA) on CT chest images and the lowest quartile defined reduced muscle mass. Sarcopenia was defined as low FFMI and handgrip strength. Regression analyses were conducted to determine predictive value of frailty, low FFMI and sarcopenia on clinical outcomes. The Cox proportional hazards model was used to analyze the impact of FFMI and frailty score on survival. The mean age was 70 years with moderate impairment in lung function (mean ppFVC 68.5%, ppDLCO 45.6%). Baseline forced vital capacity (p

Laser hot wire directed energy deposition (LHW-DED) is a layer-by-layer additive manufacturing technique that permits the fabrication of large-scale Ti-6Al-4V (Ti64) components with a high deposition rate and has gained traction in the aerospace sector in recent years. However, one of the major challenges in LHW-DED Ti64 is heat accumulation, which affects the part quality, microstructure, and properties of as-built specimens. These issues require a comprehensive understanding of the layerwise heat-accumulation-driven process–structure–property relationship in as-deposited samples. In this study, a systematic investigation was performed by fabricating three Ti-6Al-4V single-wall specimens with distinct interlayer delays, i.e., 0, 120, and 300 s. The real-time acquisition of high-fidelity thermal data and high-resolution melt pool images were utilized to demonstrate a direct correlation between layerwise heat accumulation and melt pool dimensions. The results revealed that the maximum heat buildup temperature of the topmost layer decreased from 660 °C to 263 °C with an increase to a 300 s interlayer delay, allowing for better control of the melt pool dimensions, which then resulted in improved part accuracy. Furthermore, the investigation of the location-specific composition, microstructure, and mechanical properties demonstrated that heat buildup resulted in the coarsening of microstructures and, consequently, the reduction of micro-hardness with increasing height. Extending the delay by 120 s resulted in a 5% improvement in the mechanical properties, including an increase in the yield strength from 817 MPa to 859 MPa and the ultimate tensile strength from 914 MPa to 959 MPa. Cooling rates estimated at 900 °C using a one-dimensional thermal model based on a numerical method allowed us to establish the process–structure–property relationship for the wall specimens. The study provides deeper insight into the effect of heat buildup in LHW-DED and serves as a guide for tailoring the properties of as-deposited specimens by regulating interlayer delay.

ABSTRACT: The injury rate in agility dogs is relatively high compared to the general population. No study to date has considered the biomechanical effects of the dog walk obstacle in agility trials, highlighting a research need. This study assessed forelimb joint kinematics and peak ground reaction forces (PVF) over a dog walk agility obstacle and correlate with experience. Ten (n = 10) dogs were filmed running across a Kennel Club (KC) standard dog walk for kinematics analysis. Two pressure sensors were secured to the (1) dog walk contact area at exit and (2) ground at the end of the dog walk (landing area) for kinetics analysis. Forelimb joints angles and PVF at the contact zone at the walk exit and landing were analysed. A key finding is that the way a dog will move across the obstacle changes depending on their level of experience, with experienced dogs showing faster obstacle negotiation and increased flexion of the elbow joint compared to inexperienced competitors. Higher speeds over the dog walk also resulted in significantly increased elbow joint flexion. Another important finding is that PVF at landing are higher is dogs that are faster and also in dogs performing running technique in comparison to stopped technique. Overall, dog walk obstacle created more forelimbs joint flexion and similar PVF in comparison with previously studied agility contact obstacles which leads us to conclude that further research is required to ascertain the long term health implications for dogs used in agility trials.

The US Coast Guard Academy began adenovirus vaccination of incoming cadets in 2022. Of 294 vaccine recipients, 15%–20% had mild respiratory or systemic symptoms within 10 days postvaccination but no serious adverse events after 90 days. Our findings support the continued use of adenovirus vaccines in congregate military settings.

Abstract Background Incline treadmill and underwater treadmill (UWTM) exercises are common canine rehabilitation modalities , which are often used in isolation in dogs recovering from spinal surgery. Early use of an incline during UWTM exercise may have the potential to improve rehabilitation outcomes in dogs, but, it is hypothesised that dorsoventral movement of the spine may be excessive meaning it is unsuitable in some circumstances. Objectives The purpose of this study was to identify changes in canine spinal kinematics in dogs when using a dry treadmill at different angles of incline compared to an underwater treadmill using the same inclines. Methods Eight dogs were encouraged to walk on a dry, horizontal, underwater treadmill as well as under the same conditions with both a 10% and 20% incline. This was then repeated at a 10% and 20% incline with the addition of water to hock level. Data were collected using reflective anatomical markers placed at the occipital protuberance, T1, T13, L3, L7 and sacral apex, captured by a high‐speed camera facing the lateral aspect of the treadmill. Dorsoventral motion of the spine as well as flexion, extension and range of motion (ROM) of T1, T13, L3 and L7 were recorded. Results We found significant differences in dorsoventral spinal ROM at T1, L3 and L7, but no significant differences in T13 ROM. No significant differences were found in flexion and extension of any of the joints assessed when comparing dry conditions to the use of water (P>0.05). Conclusions The lack of significant differences in joint flexion and extension at T1, T13, L3 and L7 indicates the potential safe use of combining underwater treadmill and incline exercise in canine rehabilitation. However, a lack of uniformity in results makes distinguishing any patterns of significance difficult. More research is needed to establish the effects of these exercises in additional planes of motion before a treatment protocol can be established.

Abstract Background In rural areas of low- and middle- income countries, mental health care is often unavailable and inaccessible, and stigma is a major barrier to treatment. Destigmatization can increase treatment-seeking attitudes, community support, and acceptance of individuals suffering from mental illness. This study’s primary objective was to evaluate the impact of a community-led, theater-based destigmatization campaign for mental illness conducted in the Busoga region of Eastern Uganda. Methods One hundred residents of the Busoga region were randomly selected via cluster sampling to complete a structured questionnaire assessing mental health stigma. Four focus groups were conducted for qualitative data on mental health stigma. Common misconceptions and specific points of stigma were identified from these responses, and local village health team personnel developed and performed a culturally-adapted theatrical performance addressing these points. Changes in perceptions of mental illness were measured among 57 attendees using two measures, the Broad Acceptance Scale (designed to reflect factors that contribute to structural stigma) and Personal Acceptance Scale (designed to reflect factors that contribute to interpersonal, or public stigma), before and after the performance. Results There was a significant increase in acceptance according to the Broad Acceptance Scale (p

Much of modern science takes place in a computational environment, and, increasingly, that environment is programmed using R, Python, or Julia. Furthermore, most scientific data now live on the cloud, so the first step in many workflows is to query a cloud database and load the response into a computational environment for further analysis. Thus, tools that facilitate programmatic data retrieval represent a critical component in reproducible scientific workflows. Earth science is no different in this regard. To fulfill that basic need, we developed R, Python, and Julia packages providing programmatic access to the U.S. Geological Survey’s National Water Information System database and the multi-agency Water Quality Portal. Together, these packages create a common interface for retrieving hydrologic data in the Jupyter ecosystem, which is widely used in water research, operations, and teaching. Source code, documentation, and tutorials for the packages are available on GitHub. Users can go there to learn, raise issues, or contribute improvements within a single platform, which helps foster better engagement and collaboration between data providers and their users.

BackgroundThere is a need to better understand the relationship between the diet, the gut microbiota and mental health. Metabolites produced when the human gut microbiota metabolize amino acids may enter the bloodstream and have systemic effects. We hypothesize that fermentation of amino acids by a resistant protein-primed gut microbiota could yield potentially toxic metabolites and disturb the availability of neurotransmitter precursors to the brain. However, these mechanisms are challenging to investigate via typical in vitro and clinical methods.MethodsWe developed a novel workflow using 14C radiolabeling to investigate complex nutrient-disease relationships. The first three steps of the workflow are reported here. α-Linolenic acid (ALA) was used as a model nutrient to confirm the efficacy of the workflow, and tyrosine (Tyr) was the test nutrient. 14C-Tyr was administered to male weanling pigs fed a high resistant protein diet, which primed the gut microbiota for fermenting protein. The hypotheses were; (1) that expected biodistribution of 14C-ALA would be observed, and (2) that radioactivity from 14C-Tyr, representing Tyr and other amino acids released from resistant protein following gut microbial fermentation, would be bioavailable to the brain.ResultsRadioactivity from the 14C-ALA was detected in tissues reflecting normal utilization of this essential fatty acid. Radioactivity from the 14C-Tyr was detected in the brain (0.15% of original dose).ConclusionMetabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to affect brain function. By extension, resistant proteins in the diet reaching the gut microbiota, also have potential to release metabolites that can potentially affect brain function. The high specificity of detection of 14C radioactivity demonstrates that the proposed workflow can similarly be applied to understand other key diet and health paradigms.

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.

Background. Water treadmill (WT) exercise is a popular modality for the training and rehabilitation of horses. However, evidence-based literature regarding the use of WT exercise, particularly using inclines, is lacking. Objectives. The aim of this study was to assess the effect of recurring inclined WT sessions on equine epaxial muscle development. Methods. Six horses completed 24 sessions of 15 minutes of WT activity over four weeks. Horses walked with water at the midcannon level at a treadmill incline of 4%. Back traces were measured at three and seven centimetres ventral to the dorsal midline at T5, T9, T14, and T18, prior to the first session (W0) and weekly for 4 weeks (W1–4). Results. Overall, the back traces demonstrated progressive increases in muscle development (p

IntroductionUnderstanding how environmental interact challenges with genetic predispositions modulate health and wellbeing is an important area of biomedical research. Circadian rhythms play an important role in coordinating the multitude of cellular and tissue processes that organisms use to predict and adapt to regular changes in the environment, and robust circadian rhythms contribute to optimal physiological and behavioral responses to challenge. However, artificial lighting and modern round-the-clock lifestyles can disrupt the circadian system, leading to desynchronization of clocks throughout the brain and body. When coupled with genetic predispositions, circadian desynchronization may compound negative outcomes. Polymorphisms in the brain-derived neurotrophic (BDNF) gene contribute to variations in neurobehavioral responses in humans, including impacts on sleep, with the common Val66Met polymorphism linked to several negative outcomes.MethodsWe explored how the Val66Met polymorphism modulates the response to environmental circadian desynchronization (ECD) in a mouse model. ECD was induced by housing adult male mice in a 20 h light-dark cycle (LD10:10; 10 h light, 10 h dark). Sleep and circadian activity were recorded in homozygous (Met) mice and their wild-type (Val) littermates in a standard 24 h LD cycle (LD12:12), then again after 20, 40, and 60 days of ECD.ResultsWe found ECD significantly affected the sleep/wake timing in Val mice, however, Met mice maintained appropriate sleep timing after 20 days ECD, but not after 40 and 60 days of ECD. In addition, the rise in delta power at lights on was absent in Val mice but was maintained in Met mice. To elucidate the circadian and homeostatic contribution to disrupted sleep, mice were sleep deprived by gentle handling in LD12:12 and after 20 days in ECD. Following 6 h of sleep deprivation delta power was increased for both Val and Met mice in LD12:12 and ECD conditions. However, the time constant was significantly longer in the Val mice during ECD compared to LD12:12, suggesting a functioning but altered sleep homeostat.DiscussionThese data suggest the Val66Met mutation is associated with an ability to resist the effects of LD10:10, which may result in carriers suffering fewer negative impacts of ECD.

The professionalisation of the police in Canada, and England and Wales has highlighted a gap in the education levels of new recruits and current serving police officers, motivating many of these officers to complete a university degree. The prior experience and training of these officers can be utilised as academic and operational credit against the learning outcomes of undergraduate programs and both countries use a system to recognise and dispense this award. In Canada this is called Prior Learning Assessment Recognition (PLAR) and in England and Wales, Accredited Prior Experiential Learning (APEL). The College of Policing also offers a system of Recognised Prior Learning (RPL) which tailors support to officers in accessing higher education programs. This paper examines how the two countries methods support the bridging of the academic gap between new recruit and long-serving officers, supporting the professionalisation transition of the police force to produce effective 21st century officers. Formalized partnerships between academic institutions and police services are rare, but the need for academic institutions to develop pathways for officers to complete higher level education is a positive step forward in the process. This review highlights how Canada has yet to engage with academia in the professionalisation process in the same way as England and Wales.

The COVID-19 pandemic changed our world as we know it and continues to be a global problem three years since the pandemic began. Several vaccines were produced, but there was a considerable amount of societal turmoil surrounding them that has affected the way people view not only COVID-19 vaccines but all vaccines. We used a survey to compare how attitudes towards vaccination have changed in college students during the pandemic. An initial survey was administered in 2021, then a follow-up in 2022. Out of 316 respondents who answered the first survey, 192 completed the follow-up. The survey was designed to measure trends in changes to vaccine attitudes since the COVID-19 pandemic began. By comparing the first survey in 2021 and the follow-up, we found that roughly 55% of respondents’ vaccine attitudes did not change, roughly 44% of respondents’ attitudes towards vaccines became more positive, and only about 1% of the respondents’ vaccine attitudes became more negative. Improved view of vaccines was associated with political views and increased trust in medicine and the healthcare system. Worsened opinions of vaccines were associated with a belief that the COVID-19 vaccine affected fertility.

Abstract Background Modelling and simulation are being increasingly utilized to support the discovery and development of new anti-malarial drugs. These approaches require reliable in vitro data for physicochemical properties, permeability, binding, intrinsic clearance and cytochrome P450 inhibition. This work was conducted to generate an in vitro data toolbox using standardized methods for a set of 45 anti-malarial drugs and to assess changes in physicochemical properties in relation to changing target product and candidate profiles. Methods Ionization constants were determined by potentiometric titration and partition coefficients were measured using a shake-flask method. Solubility was assessed in biorelevant media and permeability coefficients and efflux ratios were determined using Caco-2 cell monolayers. Binding to plasma and media proteins was measured using either ultracentrifugation or rapid equilibrium dialysis. Metabolic stability and cytochrome P450 inhibition were assessed using human liver microsomes. Sample analysis was conducted by LC–MS/MS. Results Both solubility and fraction unbound decreased, and permeability and unbound intrinsic clearance increased, with increasing Log D7.4. In general, development compounds were somewhat more lipophilic than legacy drugs. For many compounds, permeability and protein binding were challenging to assess and both required the use of experimental conditions that minimized the impact of non-specific binding. Intrinsic clearance in human liver microsomes was varied across the data set and several compounds exhibited no measurable substrate loss under the conditions used. Inhibition of cytochrome P450 enzymes was minimal for most compounds. Conclusions This is the first data set to describe in vitro properties for 45 legacy and development anti-malarial drugs. The studies identified several practical methodological issues common to many of the more lipophilic compounds and highlighted areas which require more work to customize experimental conditions for compounds being designed to meet the new target product profiles. The dataset will be a valuable tool for malaria researchers aiming to develop PBPK models for the prediction of human PK properties and/or drug–drug interactions. Furthermore, generation of this comprehensive data set within a single laboratory allows direct comparison of properties across a large dataset and evaluation of changing property trends that have occurred over time with changing target product and candidate profiles.

Background Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality. Aims This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality. Method A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013. Results Nutrient intake in the sample largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P > 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance. Conclusions This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy samples, but limitations must be noted regarding comparability. Future studies employing larger sample sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.

Secondary active transporters reside in cell membranes transporting polar solutes like amino acids against steep concentration gradients, using electrochemical gradients of ions as energy sources. Commonly, ensemble-based measurements of radiolabeled substrate uptakes or transport currents inform on kinetic parameters of transporters. Here we describe a fluorescence-based functional assay for glutamate and aspartate transporters that provides single-transporter, single-transport cycle resolution using an archaeal elevator-type sodium and aspartate symporter GltPh as a model system. We prepare proteo-liposomes containing reconstituted purified GltPh transporters and an encapsulated periplasmic glutamate/aspartate-binding protein, PEB1a, labeled with donor and acceptor fluorophores. We then surface-immobilize the proteo-liposomes and measure transport-dependent Fluorescence Resonance Energy Transfer (FRET) efficiency changes over time using single-molecule Total Internal Reflection Fluorescence (TIRF) microscopy. The assay provides a 10-100 fold increase in temporal resolution compared to radioligand uptake assays. It also allows kinetic characterization of different transport cycle steps and discerns kinetic heterogeneities within the transporter population.

Abstract 1. Around the globe, instream infrastructures such as dams, weirs, and culverts associated with roads are wide‐spread and continue to be constructed. There is limited documentation of smaller infrastructure because of mixed regulation and laws related to instream construction, as well as difficulty in documentation because of their size and frequency in waterscapes. 2. We reviewed evidence of different methods used to quantify environmental and ecological responses (positive, negative, or neutral) to dams, weirs, and culverts. 3. Most studies (78% of 87) in our review evaluated dams or weirs, and more than half evaluated environmental or ecological responses at more than one of these structures. More than half of the studies used spatial (disturbed–undisturbed in the same or a different catchment) rather than temporal (before–after construction or before–after destruction) comparative methods. Evaluations also tended to focus on ecological variables, most specifically on fish community responses (just over a quarter) to infrastructure. 4. More than half (58%) of the evaluations at dams, weirs, or culverts reported negative environmental or ecological responses. Discrepancies in responses recorded for different infrastructure types could be partially explained by the focus on ecological responses in reviewed studies and related metrics used for evaluations (e.g. biotic groups, richness, and abundance), the imbalance of studies at different infrastructure types, and discrepancies in spatial and temporal scales of evaluations compared to those at which the variables respond to infrastructure. 5. Despite the abundance of road culverts greatly exceeding the number of small or large dams worldwide, they were evaluated in only 22% of studies that we reviewed. Our findings underscore the need for studies to not only better understand local but also cumulative impacts of these smaller infrastructure, as these could be greater than those caused by large infrastructure depending on their location, density, and type, among other factors. Such studies are needed to inform infrastructure planning and watershed management.

In this review we summarize the work conducted over the past decade that has advanced our knowledge of pulmonary diseases associated with exposure to beryllium that has provided a molecular-based understanding of the chemistry, immunopathology, and immunogenetics of beryllium toxicity. Beryllium is a strong and lightweight metal that generates and reflects neutrons, resists corrosion, is transparent to X-rays, and conducts electricity. Beryllium is one of the most toxic elements on the periodic table, eliciting in susceptible humans (a) an allergic immune response known as beryllium sensitization (BeS); (b) acute beryllium disease, an acutely toxic, pneumonitis-like lung condition resulting from exposure to high beryllium concentrations that are rarely seen in modern industry; and (c) chronic beryllium disease (CBD) following either high or very low levels of exposure. Because of its exceptional strength, stability, and heat-absorbing capability, beryllium is used in many important technologies in the modern world. In the early 1940s, beryllium was recognized as posing an occupational hazard in manufacturing and production settings. Although acute beryllium disease is now rare, beryllium is an insidious poison with a latent toxicity and the risk of developing CBD persists. Chronic beryllium disease-a systemic granulomatous lung disorder caused by a specific delayed immune response to beryllium within a few months to several decades after exposure-has been called the "unrecognized epidemic". Although not a disease in itself, BeS, the innate immune response to beryllium identified by an abnormal beryllium lymphocyte proliferation test result, is a population-based predictor of CBD. Genetic susceptibility to CBD is associated with alleles of the major histocompatibility gene, human leukocyte antigen DP (HLA-DP) containing glutamic acid at the 69th position of the beta chain (HLA-DPbeta-E69). Other genes are likely to be involved in the disease process, and research on this issue is in progress. The current Occupational Safety & Health Administration permissible exposure limit of 2 microg/m3 has failed to protect workers from BeS/CBD. As a safe exposure limit that will not lead to BeS or CBD has not yet been determined, the realization that the risk of CBD persists has led to a renaissance in research on the effects of the metal on human health. Current data support further reductions in exposure levels to help minimize the incidence of CBD. Steps that would directly impact both the power of epidemiologic studies and the cost of surveillance would be to develop and validate improved screening and diagnostic tests, and to identify more genetic factors that affect either sensitization or disease process. The major focus of this review is the recent research on the cellular and molecular basis of beryllium sensitization and disease, using a multidisciplinary approach of bioinorganic chemistry and immunology. First we present a historical background of beryllium exposure and disease, followed by occurrence of beryllium in the environment, toxicokinetics, biological effects, beryllium lung disease, and other human health effects. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are a heterogeneous collection of hematopoietic disorders characterized by low blood counts and a tendency to progress to acute myeloid leukemia. Treatment options have increased over the past 10 years, and many new agents are currently being investigated. In this article, we review the diagnosis of MDS, prognostic systems, and treatment options, including supportive care, erythropoiesis-stimulating agents, antithymocyte globulin, lenalidomide, azacitidine, decitabine, intensive chemotherapy, and hematopoietic cell transplantation. [ABSTRACT FROM AUTHOR]

Objective: This study compares once-daily ropinirole 24-h prolonged release and three-times-daily ropinirole immediate release in patients with early Parkinson's disease.Methods: This multicentre, double-blind, non-inferiority crossover study involved 161 patients randomized to one of four formulation sequences: (1) immediate release-immediate release-prolonged release; (2) immediate release-prolonged release-prolonged release; (3) prolonged release-prolonged release-immediate release; (4) prolonged release-immediate release-immediate release. During a 12-week dose-titration period, ropinirole immediate release was titrated according to the approved labelling; titration of ropinirole 24-h prolonged release started at a higher dose and was more rapid. Patients then entered three consecutive, flexible-dose, 8-week maintenance periods. At the end of the first maintenance period, half of the patients in each formulation group switched to the same or closest dose of the alternative formulation; remaining patients switched at the end of the second maintenance period.Results: At the end of titration, before the first dose switch, there were substantial reductions in mean Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. During maintenance periods, both groups showed similar efficacy on the UPDRS motor score. Overall mean (standard error) change from period baseline was -0.1 (0.28) for ropinirole 24-h prolonged release, and 0.6 (0.30) for ropinirole immediate release (adjusted mean treatment difference -0.7; 95% confidence interval [CI]: -1.51, 0.10; p = 0.0842). The upper limit of the 95% CI was less than the predefined threshold of 3 points for non-inferiority. Ropinirole 24-h prolonged release was well-tolerated when titrated more rapidly than ropinirole immediate release; overnight switching between formulations was also well-tolerated. Study limitations included complexity of the non-inferiority study design and the forced dose-titration schedule.Conclusion: Ropinirole 24-h prolonged release was effective and well-tolerated in patients with early Parkinson's disease. [ABSTRACT FROM AUTHOR]

Rationale: The lungs are a common site of serious infection in both healthy and immunocompromised subjects, and the most likely route of delivery of a bioterror agent. Since the airway epithelium shows great structural plasticity in response to inflammatory stimuli, we hypothesized it might also show functional plasticity.Objectives: To test the inducibility of lung defenses against bacterial challenge.Methods: Mice were treated with an aerosolized lysate of ultraviolet-killed nontypeable (unencapsulated) Haemophilus influenzae (NTHi), then challenged with a lethal dose of live Streptococcus pneumoniae (Spn) delivered by aerosol.Measurements and Main Results: Treatment with the NTHi lysate induced complete protection against challenge with a lethal dose of Spn if treatment preceded challenge by 4 to 24 hours. Lesser levels of protection occurred at shorter (83% at 2 h) and longer (83% at 48-72 h) intervals between treatment and challenge. There was also some protection when treatment was given 2 hours after challenge (survival increased from 14 to 57%), but not 24 hours after challenge. Protection did not depend on recruited neutrophils or resident mast cells and alveolar macrophages. Protection was specific to the airway route of infection, correlated in magnitude and time with rapid bacterial killing within the lungs, and was associated with increases of multiple antimicrobial polypeptides in lung lining fluid.Conclusions: We infer that protection derives from stimulation of local innate immune mechanisms, and that activated lung epithelium is the most likely cellular effector of this response. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value. [ABSTRACT FROM AUTHOR]

In Classroom Exercises for Entrepreneurship: A Cross-Disciplinary Approach, James D. Hart offers an expansive pedagogy for entrepreneurship training through creative play and experiential learning.

Molecular spectroscopic detection techniques, such as Fourier transform infrared spectroscopy (FTIR), provides additional specificity for isomers where often mass spectrometry (MS) fails, due to similar fragmentation patterns. A hyphenated system of gas chromatography (GC) with FTIR via a light-pipe interface is reported in this study to explore a number of GC–FTIR analytical capabilities. Various compound classes were analyzed—aromatics, essential oils and oximes. Variation in chromatographic peak parameters due to the light-pipe was observed via sequentially-located flame ionization detection data. Unique FTIR spectra were observed for separated mixtures of essential oil isomers having similar mass spectra. Presentation of GC×FTIR allows a ‘comprehensive’-style experiment to be developed. This was used to obtain spectroscopic/separation profiles for interconverting oxime species with their individual spectra in the overlap region being displayed on a color contour plot. Partial least square regression provides multivariate quantitative analysis of co-eluting cresol isomers derived from GC–FTIR data. The model resulted in an R2 of 0.99. Prediction was obtained with R2 prediction value of 0.88 and RMSEP of 0.57, confirming the method’s suitability. This study explores the potential of GC–FTIR hyphenation and re-iterates its value to derive unambiguous and detailed molecular information which is complementary to MS.

Unlocking the full potential of pathology data by gaining computational access to histological pixel data and metadata (digital pathology) is one of the key promises of computational pathology. Despite scientific progress and several regulatory approvals for primary diagnosis using whole-slide imaging, true clinical adoption at scale is slower than anticipated. In the U.S., advances in digital pathology are often siloed pursuits by individual stakeholders, and to our knowledge, there has not been a systematic approach to advance the field through a regulatory science initiative. The Alliance for Digital Pathology ( the Alliance) is a recently established, volunteer, collaborative, regulatory science initiative to standardize digital pathology processes to speed up innovation to patients. The purpose is: (1) to account for the patient perspective by including patient advocacy; (2) to investigate and develop methods and tools for the evaluation of effectiveness, safety, and quality to specify risks and benefits in the precompetitive phase; (3) to help strategize the sequence of clinically meaningful deliverables; (4) to encourage and streamline the development of ground-truth data sets for machine learning model development and validation; and (5) to clarify regulatory pathways by investigating relevant regulatory science questions. The Alliance accepts participation from all stakeholders, and we solicit clinically relevant proposals that will benefit the field at large. The initiative will dissolve once a clinical, interoperable, modularized, integrated solution (from tissue acquisition to diagnostic algorithm) has been implemented. In times of rapidly evolving discoveries, scientific input from subject-matter experts is one essential element to inform regulatory guidance and decision-making. The Alliance aims to establish and promote synergistic regulatory science efforts that will leverage diverse inputs to move digital pathology forward and ultimately improve patient care.