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Evidence of vicarious exposure to racism has primarily been garnered from in-group racial-ethnic samples to convey its harmful psychological impacts on individuals who share identities with those who are directly experiencing the racist act being observed. The extent to which this evidence applies to out-group members exposed to vicarious racism is underexamined. The present study investigated the extent to which vicarious exposure to racialized violence in policing leading to the death of George Floyd predicted negative affect among a sample of undergraduate students when accounting for other factors that may contribute to negative affect. A sample (N = 683) of nonhomogeneous racial-ethnic (67% People of Color; 33% White) undergraduate students aged 18 to 41 completed an online survey assessing demographic characteristics, vicarious racism exposure, everyday discrimination exposure, and affect during the summer and fall of 2020. Bivariate analyses indicated racial-ethnic disparities in negative affect among the sample. After controlling for race-ethnicity, gender identity, sexual identity, and everyday discrimination, a hierarchical linear regression analysis indicated that exposure to vicarious racialized violence in policing significantly predicted increased levels of negative affect. These findings provide vital insight into the harmful psychological impacts of vicarious exposure to racialized violence on individuals in the U.S. which has individual, population, and public health implications. [ABSTRACT FROM AUTHOR]

The objective of the Earth Cloud, Aerosol, and Radiation Explorer (EarthCARE) mission is to infer attributes of cloud, aerosol, precipitation, and radiation from observations made by four complementary instruments. This requires the development of single-instrument and multiple-instrument (i.e. synergistic) retrieval algorithms that employ measurements made by one, or more, of EarthCARE's cloud-profiling radar (CPR), atmospheric lidar (ATLID), and multi-spectral imager (MSI); its broadband radiometer (BBR) places the retrieved quantities in the context of the surface–atmosphere radiation budget. To facilitate the development and evaluation of ESA's EarthCARE production model prior to launch, sophisticated instrument simulators were developed to produce realistic synthetic EarthCARE measurements for simulated conditions provided by cloud-resolving models. While acknowledging that the physical and radiative representations of cloud, aerosol, and precipitation in the test scenes are based on numerical models, the opportunity to perform detailed evaluations wherein the "truth" is known provides insights into the performance of EarthCARE's instruments and retrieval algorithms. This level of omniscience will not be available for the evaluation of in-flight EarthCARE retrieval products, even during validation activities coordinated with ground-based and airborne measurements. In this study, we compare EarthCARE retrieval products both statistically across all simulated scenes and from a specific time series from a single scene. For ice clouds, it is shown that retrieved profiles of ice water content and effective particle size made by the ATLID-CPR-MSI cloud, aerosols, and precipitation (ACM-CAP) synergistic algorithm are consistently more accurate than those from its single-instrument counterparts. While liquid clouds are often difficult to detect from satellite-borne sensors, especially for multi-layered clouds, ACM-CAP benefits from combined constraints from lidar backscatter, solar radiances, and radar-path-integrated attenuation but still exhibits non-trivial random error. For precipitation retrievals, the CPR cloud and precipitation product (C-CLD) and ACM-CAP have a similar performance when well-constrained by CPR measurements. The greatest differences are in coverage, with ACM-CAP reporting retrievals in the melting layer, and in heavy precipitation, where CPR signals are dominated by multiple scattering and attenuation. Aerosol retrievals from ATLID compensate for a high degree of measurement noise in a number of ways, with the ATLID extinction, backscatter, and depolarisation (A-EBD) product and ACM-CAP demonstrating similar performance. The multi-spectral imager (MSI) cloud optical properties (M-COP) product performs very well for unambiguous cloud layers. Similarly, the MSI aerosol optical thickness (M-AOT) product performs well when radiances are unaffected by cloud, but both products provide little information about vertical profiles of properties. Finally, a summary of the performance of all retrieval products and their random errors is provided. [ABSTRACT FROM AUTHOR]

Small clusters have captured the imaginations of experimentalists and theorists alike for decades. In addition to providing insight into the evolution of properties between the atomic or molecular limits and the bulk, small clusters have revealed a myriad of fascinating properties that make them interesting in their own right. This perspective reviews how the application of anion photoelectron (PE) spectroscopy, typically coupled with supporting calculations, is particularly well-suited to probing the molecular and electronic structure of small clusters. Clusters provide a powerful platform for the study of the properties of local phenomena (e.g., dopants or defect sites in heterogeneous catalysts), the evolution of the band structure and the transition from semiconductor to metallic behavior in metal clusters, control of electronic structures of clusters through electron donating or withdrawing ligands, and the control of magnetic properties by interactions between the photoelectron and remnant neutral states, among other important topics of fundamental interest. This perspective revisits historical, groundbreaking anion PE spectroscopic finding and details more recent advances and insight gleaned from the PE spectra of small covalently or ionically bound clusters. The properties of the broad range of systems studied are uniquely small-cluster like in that incremental size differences are associated with striking changes in stability, electronic structures, and symmetry, but they can also be readily related to larger or bulk species in a broader range of materials and applications. [ABSTRACT FROM AUTHOR]

Clinical Scenario: Lower-extremity injuries in the United States costs millions of dollars each year. Athletes should be screened for neuromuscular deficits and trained to correct them. The tuck jump assessment (TJA) is a plyometric tool that can be used with athletes. Clinical Question: Does the TJA demonstrate both interrater and intrarater reliability in healthy individuals? Summary of Key Findings: Four of the 5 articles included in this critically appraised topic showed good to excellent reliability; however, caution should be taken in interpreting these results. Although composite scores of the TJA were found to be reliable, individual flaws do not demonstrate reliability on their own, with the exception of knee valgus at landing. Aspects of the TJA itself, including rater training, scoring system, playback speed, volume, and number of views allotted, need to be standardized before the reliability of this clinical assessment can be further researched. Clinical Bottom Line: The TJA has shown varying levels of reliability, from poor to excellent, for both interrater and intrarater reliability, given current research. Strength of Recommendation: According to the Centre for Evidence Based Medicine levels of evidence, there is level 2b evidence for research into the reliability of the TJA. This evidence has been demonstrated in elite, adolescent, and college-level athletics in the United Kingdom, Spain, and the United States. The recommendation of level 2b was chosen because these studies utilized cohort design for interrater and intrarater reliability across populations. An overall grade of B was recommended because there were consistent level 2 studies. [ABSTRACT FROM AUTHOR]

Mixed-metal oxides have proven to be effective catalysts for the hydrogen evolution reaction, often outperforming either of the binary metal oxides. The reactivity of MnxMoOy− (x = 1, 2; y = 3, 4) clusters toward H2O was investigated via time-of-flight mass spectrometry with clear evidence of cluster oxidation and corresponding H2 production, specifically for MnxMoO3− (x = 1, 2) clusters. Unlike previously studied MoxOy− clusters, which assumed a broad distribution of stoichiometries (typically x ≤ y ≤ 3x), both MnMoOy− and Mn2MoOy− preferentially formed y = 3 and 4 compositions in significant quantities under our source conditions. The electronic and molecular structures of the MnxMoOy (x = 1, 2; y = 3, 4) anion and neutral clusters were probed with anion photoelectron spectroscopy and analyzed with supporting density functional theory calculations. Our studies suggest that both metal centers are involved in initial cluster–water complex formation, while Mo is the center that undergoes oxidation; hence, reactivity terminates when Mo is saturated in its highest oxidation state of +6. Across these four clusters, Mn remains relatively reduced and is stable in a high-spin electronic configuration. The preferential reactivity of water molecules toward the Mo center rather than Mn is rationalized by the much lower relative oxophilicity of Mn. [ABSTRACT FROM AUTHOR]

ACM-CAP provides a synergistic best-estimate retrieval of all clouds, aerosols, and precipitation detected by the atmospheric lidar (ATLID), cloud-profiling radar (CPR), and multi-spectral imager (MSI) aboard EarthCARE (Earth Cloud Aerosol and Radiation Explorer). While synergistic retrievals are now mature in many contexts, ACM-CAP is unique in that it provides a unified retrieval of all hydrometeors and aerosols. The Cloud, Aerosol, and Precipitation from mulTiple Instruments using a VAriational TEchnique (CAPTIVATE) algorithm allows for a robust accounting of observational and retrieval errors and the contributions of passive and integrated measurements and for enforcing physical relationships between components (e.g. the conservation of precipitating mass flux through the melting layer). We apply ACM-CAP to EarthCARE scenes simulated from numerical weather model forecasts and evaluate the retrievals against "true" quantities from the numerical model. The retrievals are well-constrained by observations from active and passive instruments and overall closely resemble the bulk quantities (e.g. cloud water content, precipitation mass flux, and aerosol extinction) and microphysical properties (e.g. cloud effective radius and median volume diameter) from the model fields. The retrieval performs best where the active instruments have a strong and unambiguous signal, namely in ice clouds and snow, which is observed by both ATLID and CPR, and in light to moderate rain, where the CPR signal is strong. In precipitation, CPR's Doppler capability permits enhanced retrievals of snow particle density and raindrop size. In complex and layered scenes where ATLID is obscured, we have shown that making a simple assumption about the presence and vertical distribution of liquid cloud in rain and mixed-phase clouds allows improved assimilation of MSI solar radiances. In combination with a constraint on the CPR path-integrated attenuation from the ocean surface, this leads to improved retrievals of both liquid cloud and rain in midlatitude stratiform precipitation. In the heaviest precipitation, both active instruments are attenuated and dominated by multiple scattering; in these situations, ACM-CAP provides a seamless retrieval of cloud and precipitation but is subject to a high degree of uncertainty. ACM-CAP's aerosol retrieval is performed in hydrometeor-free parts of the atmosphere and constrained by ATLID and MSI solar radiances. While the aerosol optical depth is well-constrained in the test scenes, there is a high degree of noise in the profiles of extinction. The use of numerical models to simulate test scenes has helped to showcase the capabilities of the ACM-CAP clouds, aerosols, and precipitation product ahead of the launch of EarthCARE. [ABSTRACT FROM AUTHOR]

• A unified gross traction algorithm is proposed for braked, towed, and powered wheels on clay. • The model is developed using the Database Records for Off-road Vehicle Environments. • The algorithm employs the ratio of average contact pressure to cone index. • The new equation can be implemented in off-road mobility models. A characteristic curve is presented for predicting gross traction of a wheel over a range of powered, towed, and braked modes on clay soils for slip ranging from positive 100% powered slip to negative 100% skid slip. The characteristic curve is a unified approach that relates the ratio of the contact pressure of the wheel to soil strength and predicts the gross traction coefficient over a continuous range of slip. The unified equation is defined by five inflection points: maximum/minimum traction, traction at zero slip, max change in traction with slip, and a shape factor coefficient. The inflection points aim to simplify the calibration of gross traction, slip, soil strength, and contact pressure by using functions adaptable to machine learning. The unified equation is comparable to historic traction equations but is unique in its ability to predict asymmetric braking and powered gross traction. The unified equation is supported and substantiated via error analysis by utilizing the Database Records for Off-road Vehicle Environments (DROVE) – a database constructed around the archived laboratory and field tests for wheels and tracks operating on different soils. The accuracy of the proposed model is assessed and compared to other conventional equations such as the Brixius equation and Maclaurin's extension of the Pacejka equation for off-road traction. [ABSTRACT FROM AUTHOR]

Objectives: Huntington's disease (HD) is a neurodegenerative disease in which cognitive and behavioural symptoms impair the performance of instrumental activities of daily living, including the handling of finances. We sought to determine the prevalence of financial dysfunction in HD, and the demographic and clinical predictors of such impairments. Methods: We analysed longitudinal data for pre-manifest gene carriers and HD patients from the Enroll-HD dataset. Financial dysfunction was determined by finance-related items in the Total Functional Capacity (TFC) and Functional Assessment (FA) scales. A binary logistical regression model was used to investigate the predictive value of demographic and clinical factors for the development of financial dysfunction. Results: Financial impairment was found to be common in HD gene carriers, and over half required financial assistance within 5 years from diagnosis. Cognitive impairment, apathy, unemployment and disease severity predicted financial dysfunction in manifest patients. For pre-manifest patients, the predictors were proximity to disease onset and depression. Conclusions: Loss of financial autonomy is common in HD, and cognitive and psychiatric factors are important in its development. Clinicians must be vigilant to identify patients that may be vulnerable to financial exploitation. [ABSTRACT FROM AUTHOR]

Direct exposure to gender identity-related discrimination and erasure among the transgender and gender independent (TGI) population are associated with healthcare underutilization, which may further exacerbate the health disparities that exist between this population and cisgender individuals in the United States (U.S.). Although the impacts of direct exposure to healthcare discrimination and erasure may have on TGI individuals are known, exposure to such harm vicariously (i.e., through observation or report) is underexplored. The present study examined the relationships among direct and vicarious gender identity-related healthcare discrimination and erasure exposure and past-year healthcare utilization. Gender identity-based mistrust in healthcare was also assessed, as a mechanism through which direct and vicarious gender identity-related healthcare discrimination and erasure predict healthcare utilization behaviors among a sample (N = 385) of TGI adults in the U.S., aged 18 to 71 recruited online. Results indicated direct lifetime and vicarious healthcare discrimination and erasure exposure significantly predicted past-year healthcare underutilization when participants anticipated encountering gender identity-related healthcare discrimination. Mediational analyses indicated that higher levels of exposure to direct lifetime and vicarious healthcare discrimination and erasure were related to higher levels of mistrust in healthcare, through which past-year underutilization was significantly related. These findings are vital to informing healthcare practice and policy initiatives aimed at ensuring the barriers that deleteriously influence the accessibility of healthcare among TGI individuals are ameliorated. • TGI adults reported an average of 3.5 direct, 5 vicarious forms of healthcare discrimination. • TGI adults experience ∼4x more healthcare discrimination than general population. • 29% of TGI adults report avoiding needed healthcare in the prior year. • Medical mistrust is related to direct/vicarious TGI discrimination and erasure. [ABSTRACT FROM AUTHOR]

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is an inherited neurodegenerative disease characterised by neuropsychiatric symptoms, a movement disorder (most commonly choreiform) and progressive cognitive impairment. The diagnosis is usually confirmed through identification of an increased CAG repeat length in the huntingtin gene in a patient with clinical features of the condition. Though diagnosis is usually straightforward, unusual presentations can occur, and it can be difficult to know when someone has transitioned from being an asymptomatic carrier into the disease state. This has become increasingly important recently, with several putative disease-modifying therapies entering trials. A growing number of conditions can mimic HD, including rare genetic causes, which must be considered in the event of a negative HD genetic test. Patients are best managed in specialist multidisciplinary clinics, including when considering genetic testing. Current treatments are symptomatic, and largely directed at the chorea and neurobehavioural problems, although supporting trial evidence for these is often limited. [ABSTRACT FROM AUTHOR]

Hyperphosphatemia is present in most patients with end‐stage renal disease (ESRD) and has been associated with increased cardiovascular mortality. Phosphate binders (calcium‐based and calcium free) are the mainstay pharmacologic treatment to lower phosphorus levels in patients with ESRD. We evaluated biochemical markers of vascular calcification, inflammation, and endothelial dysfunction in patients with chronic kidney disease (CKD) treated with sevelamer carbonate (SC) versus calcium acetate (CA). Fifty patients with CKD (stages 3 and 4) were enrolled and assigned to treatment with SC and CA for 12 weeks. At the end of the study the biomarkers of vascular calcification, inflammation, and endothelial dysfunction were analyzed. A significant increase in HDL‐cholesterol was observed with SC but not with CA in patients with CKD. Treatment with SC reduced serum phosphate, calcium phosphate, and FGF‐23 levels and there was no change with CA treatment. The inflammatory markers IL‐8, IFN‐γ, and TNFα decreased with response to both treatments. The levels of IL‐6 significantly increased with CA treatment and no change was observed in the SC treatment group. SC showed favorable effects on anti‐inflammatory and vascular calcification biomarkers compared to CA treatment in patients with CKD stages 3 and 4 with normal phosphorous values. [ABSTRACT FROM AUTHOR]

Background: Prior work suggests some individual immunomarkers may be useful moderators of treatment response between antidepressant medications. The relative moderating effect of individual immunomarkers remains unclear. It is also unknown whether combinations of immunomarkers have a superior moderating effect compared to any individual immunomarker.Methods: Baseline immunomarker levels were assayed using multiplex from a subset of participants in the CO-MED trial (n = 143). Individual and combinations of 19 immunomarkers were modeled as moderators between the three treatment arms (escitalopram monotherapy, escitalopram-bupropion and venlafaxine-mirtazapine) across a variety of depression outcomes.Results: Only IL-13 demonstrated a consistent moderating effect across all depression outcome measures. High IL-13 (>20 pg/ml) was associated with higher remission rates to bupropion-escitalopram (67%) versus escitalopram (24%) whereas low IL-13 was associated higher remission rates to escitalopram (59%) versus bupropion-escitalopram (38%). A similar, but weaker moderating effect was observed with venlafaxine-mirtazapine versus escitalopram. The addition of multiple immunomarkers did not consistently improve predictive modeling.Limitations: This is a secondary analysis of a single clinical trial with a relatively small sample size per treatment arm. The testing of specific individual and combinations of biomarkers was data-driven.Conclusions: Among 19 immunomarkers, Il-13 was the best single moderator of treatment outcome. Combinations of immunomarkers were not meaningfully superior to Il-13. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy is commonly used as an adjunct to incomplete surgical excision in dogs with mast cell tumors (MCT), but the optimal dose and fractionation regimen have yet to be determined. Hypothesis: We assessed outcomes (time to local recurrence, patient survival and toxicity) of a large population of dogs with MCT that received adjunctive radiation therapy. Animals Three hundred dogs with 302 MCT treated using adjunctive radiation therapy. Methods: Retrospective observational study. Clinical records of 4 veterinary radiation centers were reviewed. Results: Local recurrence rates were similar regardless of radiation protocol with 6.6% of patients developing recurrent cutaneous MCT at a median of 526 days. Local recurrence rate was similar between high and low‐risk MCT. Mast cell tumor related death was reported in 19% of all dogs, with 13% of dogs with low‐risk MCT dying of their disease compared to 29% of dogs with high‐risk MCT. No SC MCT (SCMCT) recurred after radiation therapy and only 7% of dogs with SCMCT were reported to have died of their disease. Mild late toxicity was common in both protocols and severe late toxicity occurred in 1.9% of dogs many years after treatment. Conclusions and Clinical Importance: Our study supports the use of adjunctive radiation for the long‐term control of incompletely or narrowly excised cutaneous and SCMCT in dogs. More moderate dose and fractionation protocols may be appropriate in the adjunctive treatment of low‐risk MCT in dogs. Large multicenter prospective studies are required to establish the optimal dose and fractionation for MCT of different risk categories. [ABSTRACT FROM AUTHOR]

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience. [ABSTRACT FROM AUTHOR]

Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo-controlled, cross-over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-μg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-to-day operations. [ABSTRACT FROM AUTHOR]

• Low dose of LSD (5 and 20 mcg) enhances sustained attention. • Low dose of LSD (20 mcg) reduces speed of information processing. • Low dose of LSD affects mood states in positive directions (5, 10 and 20 mcg). • Low dose of LSD increased anxiety (5 and 20 mcg) and confusion (20 mcg). • Most apparent affects are present following 20 mcg of LSD. There is a popular interest in microdosing with psychedelics such as LSD. This practice of using one-tenth of a full psychedelic dose according to a specific dosing schedule, anecdotally enhances mood and performance. Nonetheless, controlled research on the efficacy of microdosing is scarce. The main objective of the present dose-finding study was to determine the minimal dose of LSD needed to affect mood and cognition. A placebo-controlled within-subject study including 24 healthy participants, was conducted to assess the acute effects of three LSD doses (5, 10, and 20 mcg) on measures of cognition, mood, and subjective experience, up until 6 h after administration. Cognition and subjective experience were assessed using the Psychomotor Vigilance Task, Digit Symbol Substitution Test, Cognitive Control Task, Profile of Mood States, and 5-Dimensional Altered States of Consciousness rating scale. LSD showed positive effects in the majority of observations by increasing positive mood (20 mcg), friendliness (5, 20 mcg), arousal (5 mcg), and decreasing attentional lapses (5, 20 mcg). Negative effects manifested as an increase in confusion (20 mcg) and anxiety (5, 20 mcg). Psychedelic-induced changes in waking consciousness were also present (10, 20 mcg). Overall, the present study demonstrated selective, beneficial effects of low doses of LSD on mood and cognition in the majority of observations. The minimal LSD dose at which subjective and performance effects are notable is 5 mcg and the most apparent effects were visible after 20 mcg. [ABSTRACT FROM AUTHOR]

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that typically manifests between the ages of 30 and 50 years. However, the disease can present at any age, and phenotypic differences between younger and later-onset patients have received limited attention.To compare clinical features of late- (>70 years of age) and younger-onset (<30 years of age) HD patients.Patients presenting to our regional NHS HD clinic with new-onset manifest HD diagnosed over the age of 70 years (LoHD) (n = 18) were compared with a younger cohort who developed disease under the age of 30 years (YoHD) (n = 12). Rate of progression over time on standard cognitive and motor measures were compared.At first clinic presentation, both groups had the same total UHDRS scores. However, the LoHD group had higher chorea scores (F (1,28) = 6.52, p = 0.016), while the YoHD group had more dystonia (F (1,28) = 8.69, p = 0.006) and eye movement abnormalities (F (1,28) = 16.991, p < 0.001). The YoHD group also had a greater rate of motor progression, especially for bulbar measures (F (1, 28) = 6.96, p = 0.013) and bradykinesia (F (1, 28) = 7.99, p = 0.009). No differences were found in the rate of cognitive change (F (1,21) = 1.727, p = 0.203) nor functional capacity (F (1,28) = 1.388, p = 0.249) between the groups.Phenotypic differences between YoHD and LoHD patients were found in terms of initial presentation and rate of motor progression. This has implications for therapeutic trials involving HD patients of different ages, given their different clinical features and progression. [ABSTRACT FROM AUTHOR]

Introduction: Characterise gut microbiota distributions of participants with co-occurring depression and anxiety, in those with only depression or with anxiety, and determine if gut bacteria differentially correlates with distinct clinical presentations.Methods: Participants (10 healthy controls [mean age: 33, 60% female] and 60 psychiatric subjects; major depressive disorder (comorbid with anxiety), n = 38 [mean age: 39.2, 82% female], anxiety only, n = 8 [mean age: 40.0, 100% female], depression only without anxiety, n = 14 [mean age: 41.9, 79% female]) were characterized by psychiatric assessments. Quantitative PCR and 16S rRNA sequencing were used to characterize the gut microbiota in stool samples.Results: Altered microbiota correlated with pre-defined clinical presentation, with Bacteroides (p = 0.011) and the Clostridium leptum subgroup (p = 0.023) significantly different between clinical categories. Cluster analysis of the total sample using weighted UniFrac β-diversity of the gut microbiota identified two different clusters defined by differences in bacterial distribution. Cluster 2 had higher Bacteroides (p = 0.006), and much reduced presence of Clostridales (p<0.001) compared to Cluster 1. Bifidobacterium (p = 0.0173) was also reduced in Cluster 2 compared to Cluster 1. When evaluated for clinical charateristics, anhedonia scores in Cluster 2 were higher than in Cluster 1.Limitations: The sample is smaller and predominately female.Conclusions: Reduced or absent Clostridia was consistently seen in those with depression, independent of the presence of anxiety. Conversely, reduced Bacteroides may be more associated with the presence of anxiety, independent of the presence of depression. These differences suggest that gut microbiota distribution could help clarify the underlying pathology of comorbid clinical presentation. [ABSTRACT FROM AUTHOR]

• Equations exist for the conversion of Cone Index to select Bevameter parameters. • The Cone index correlation relates to the bearing capacity Bevameter parameters Kc, K φ , and n. • Correlations do not exist between cone index and surface shear parameters c, ϕ. • The equations are supported by limited validation in select regional areas of sand and clay. This paper reviews experimental methods for the conversion of cone index measurements to bevameter parameters in support of vehicle soil/tire/track interactions for two general soil types, sand and lean clay. The accurate prediction of traction, motion resistance, and sinkage of tire/tracks off-road requires estimates of soil strength. Equipment used in the measurement of soil strength to support predictions of off-road mobility include the bevameter and the cone penetrometer. The portability of the cone penetrometer and rapid estimates of spatial/temporal variability in all terrain conditions make it an invaluable tool. The bevameter, a less portable tool, is used for the mechanical analysis of soils. The bevameter measures parameters defining soil strength in terms of cohesive modulus of soil deformation (k c), frictional modulus of soil deformation (k φ), exponent of soil sinkage (n), cohesion (c), angle of internal friction (φ), and the plate pressure at 1 in. (2.54 cm) of penetration (K) (Bekker, 1969). The field of terramechanics would greatly benefit from having the ability to convert cone penetrometer data in areas where bevameter parameters are difficult to collect. That ability to convert from cone index to bevameter parameters could be used for the large sets of existing cone index data to support determination of traction and motion resistance. This paper examines those methods for converting cone index to bevameter plate penetration parameters k c , k φ , and n. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the claim that Parkinson's disease (PD) specifically reduces religiosity religious faith and spirituality. METHODS: A longitudinal case-control study over 12 months of spirituality in 42 patients with idiopathic PD and 39 disease controls matched for age, gender, educational attainment and disability. There was no selection on grounds of religious affiliation. Participants were assessed on the Beck Depression Inventory, Medical Outcomes Score (MOS), cognitive tests including Paired Associate Learning [PAL], One Touch Stocking [OTS]) and Stroop test. Tests of spirituality were the Brief Multidimensional Measure of Religiousness and Spirituality questionnaire (BMMRS), a Mystical Experiences Questionnaire (MEQ), and the Rivermead Life Goals Score, supplemented by qualitative interview methods. RESULTS: Over one year, as expected, mobility and cognition declined in the PD group. However, there was no significant change in scores of religiosity and spirituality scores in this group. Likewise, there were no subjective reports of a decrease of interest in religious faith or spirituality, although anecdotal accounts of decreasing mobility, loss of driving ability, increasing emotional lability and tiredness meant reduced participation in some religious and spiritual practices. However, over one year there was a significant fall in controls' religiosity score due mainly to a fall in 'religious practices' with no clear underlying reason. CONCLUSIONS: Compared to non-neurological patients with similar disability, Parkinson's disease is not associated with a decline in religious faith or spirituality. Declining mobility and cognition in Parkinson's disease does not lead to diminished religiosity. [ABSTRACT FROM AUTHOR]

Background: Disturbed sleep is a core symptom of major depressive disorder (MDD), with nearly 90% of those with MDD reporting disturbed sleep. However, combining insomnia and hypersomnia into a single diagnostic domain ignores distinct biological differences between those symptom presentations. To better understand depression it may be necessary to explore these symptoms independently, beginning with the more prevalent insomnia.Method: The present study evaluated global insomnia symptom severity in a broad sample of MDD outpatients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, excluding patients who reported hypersomnia symptoms. The three insomnia-related symptoms from the 16-item Quick Inventory of Depressive Symptomatology- clinician rated (QIDS-C) were combined to create a global insomnia score to classify baseline insomnia severity. A modified depression severity score was then used to assess depression severity (mQIDS-C), excluding sleep-related items.Results: A repeated measures ANCOVA revealed a significant improvement in insomnia score over the acute phase treatment (F = 33.1, d.f. = 6, 9897, p < 0.0001). Improvement in insomnia score over the acute phase treatment remained statistically significant even after controlling for change in depression severity (p = 0.0004). Participants with one point higher insomnia score at baseline were significantly less likely to remit at study exit (odds ratio = 0.88, 95% confidence interval = 0.85, 0.92, p < 0.0001) even after controlling for baseline depression severity.Limitations: Objective confirmation of sleep profiles was not available.Conclusion: Greater severity of insomnia reduces likelihood of MDD remission, and insomnia symptoms improved independent of depression remission. [ABSTRACT FROM AUTHOR]

• Administration of THC increased striatal glutamate concentrations. • THC decreased corticostriatal functional connectivity, indicating increased dopamine. • Average glutamate changes correlated strongly with functional connectivity changes. • Functional connectivity changes correlated with subjective effects. Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that Δ9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopamine, which is implicated in the rewarding effects of cannabis. Additional evidence suggests that THC may act indirectly on dopamine firing by modulating GABA and glutamate release. This double-blind, placebo-controlled study assessed the acute influence of two doses of THC on brain kinetics of glutamate, GABA, and dopamine, in relation to behavioral outcomes, by using magnetic resonance spectroscopy and functional magnetic resonance imaging. Twenty occasional cannabis users received acute doses of cannabis (300 µg/kg THC) and placebo, in one of two dose regimes (full dose and divided dose), during two separate testing days. Administration of THC increased striatal glutamate concentrations, and dopamine as indicated by a reduction in functional connectivity (FC) between the nucleus accumbens (NAc) and cortical areas. Alterations in glutamate and FC were dose dependent and evident in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with FC alterations. Additionally, THC induced changes in FC correlated with feelings of subjective high and decreased performance on an attention task. Taken together, this suggests that THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, which is associated with an increase in striatal glutamate. [ABSTRACT FROM AUTHOR]

• Connectome fingerprints are ubiquitous to individual brain functional organisation. • Functional connectivity traits mediate inter-individual differences in behaviour. • Psychedelics such as ayahuasca produce distinct effects on functional brain organisation. • We find a reallocation of keypoint fingerprinting edges under ayahuasca. • Inter-individual differences in edge behaviour predict experiential qualities. The knowledge that brain functional connectomes are unique and reliable has enabled behaviourally relevant inferences at a subject level. However, whether such "fingerprints" persist under altered states of consciousness is unknown. Ayahuasca is a potent serotonergic psychedelic which produces a widespread dysregulation of functional connectivity. Used communally in religious ceremonies, its shared use may highlight relevant novel interactions between mental state and functional connectome (FC) idiosyncrasy. Using 7T fMRI, we assessed resting-state static and dynamic FCs for 21 Santo Daime members after collective ayahuasca intake in an acute, within-subject study. Here, connectome fingerprinting revealed FCs showed reduced idiosyncrasy, accompanied by a spatiotemporal reallocation of keypoint edges. Importantly, we show that interindividual differences in higher-order FC motifs are relevant to experiential phenotypes, given that they can predict perceptual drug effects. Collectively, our findings offer an example of how individualised connectivity markers can be used to trace a subject's FC across altered states of consciousness. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) are compounds designed to mimic the effects of existing recreational drugs (classical psychoactive substances [CPS]), while eluding established legal frameworks. Little is known about their effects and potential harms, rendering the increasing number of NPS a challenge to policy makers and researchers alike. Quantitative studies on the motives underlying NPS use are limited, though understanding them is crucial for the design of effective harm prevention strategies. The present study therefore aimed to compare motivational patterns for NPS, CPS, and legal psychoactive substance (LPS) use. An online survey including questions about lifetime drug use, demographics, and motives for use was completed by 2,319 participants of which 1,967 consented and were 18 years or older. Data on lifetime use and endorsed motives are presented for 12 psychoactive substances classified into LPS (alcohol, nicotine), CPS (cannabis, MDMA/ecstasy, amphetamines, cocaine, psilocybin, LSD, ayahuasca), and NPS (synthetic cannabinoids, stimulant, and hallucinogenic) and compared between classes. Across substances, the most frequently endorsed motives were to feel euphoric (58.0%), enhance an activity (52.3%), and broaden consciousness (48.1%). Motives for use were found to differ by substance and gender, with coping-related reasons being more frequent among female participants compared to males who indicated to use for a broad range of reasons. Motivational patterns of CPS and NPS use were largely similar to their classical analogues, this was not the case for synthetic cannabinoids, which had as main endorsed motive getting intoxicated, indiscriminate of specific qualities. This information can feed into tailoring of educational campaigns and prevention strategies. [ABSTRACT FROM AUTHOR]

Immunosuppression strategies have changed over time in pediatric heart transplantation. Thus, comorbidity profiles may have evolved. Clinical Trials in Organ Transplantation in Children-04 is a multicenter, prospective, cohort study assessing the impact of pre-transplant sensitization on outcomes after pediatric heart transplantation. This sub-study reports 1-year outcomes among recipients without pre-transplant donor-specific antibodies (DSAs). We recruited consecutive candidates (<21 years) at 8 centers. Sensitization status was determined by a core laboratory. Immunosuppression was standardized as follows: Thymoglobulin induction with tacrolimus and/or mycophenolate mofetil maintenance. Steroids were not used beyond 1 week. Rejection surveillance was by serial biopsy. There were 240 transplants. Subjects for this sub-study (n = 186) were non-sensitized (n = 108) or had no DSAs (n = 78). Median age was 6 years, 48.4% were male, and 38.2% had congenital heart disease. Patient survival was 94.5% (95% confidence interval, 90.1–97.0%). Freedom from any type of rejection was 67.5%. Risk factors for rejection were older age at transplant and presence of non-DSAs pre-transplant. Freedom from infection requiring hospitalization/intravenous anti-microbials was 75.4%. Freedom from rehospitalization was 40.3%. New-onset diabetes mellitus and post-transplant lymphoproliferative disorder (PTLD) occurred in 1.6% and 1.1% of subjects, respectively. There was no decline in renal function over the first year. Corticosteroids were used in 14.5% at 1 year. Pediatric heart transplantation recipients without DSAs at transplant and managed with a steroid avoidance regimen have excellent short-term survival and a low risk of first-year diabetes mellitus and PTLD. Rehospitalization remains common. These contemporary observations allow for improved caregiver and/or patient counseling and provide the necessary outcomes data to help design future randomized controlled trials. [ABSTRACT FROM AUTHOR]

The accurate representation of ice particles is essential for both remotely sensed estimates of clouds and precipitation and numerical models of the atmosphere. As it is typical in radar retrievals to assume that all snow is composed of aggregate snowflakes, both denser rimed snow and the mixed-phase cloud in which riming occurs may be under-diagnosed in retrievals and therefore difficult to evaluate in weather and climate models. Recent experimental and numerical studies have yielded methods for using triple-frequency radar measurements to interrogate the internal structure of aggregate snowflakes and to distinguish more dense and homogeneous rimed particles from aggregates. In this study we investigate which parameters of the morphology and size distribution of ice particles most affect the triple-frequency radar signature and must therefore be accounted for in order to carry out triple-frequency radar retrievals of snow. A range of ice particle morphologies are represented, using a fractal representation for the internal structure of aggregate snowflakes and homogeneous spheroids to represent graupel-like particles; the mass–size and area–size relations are modulated by a density factor. We find that the particle size distribution (PSD) shape parameter and the parameters controlling the internal structure of aggregate snowflakes both have significant influences on triple-frequency radar signature and are at least as important as that of the density factor. We explore how these parameters may be allowed to vary in order to prevent triple-frequency radar retrievals of snow from being over-constrained, using two case studies from the Biogenic Aerosols – Effects of Clouds and Climate (BAECC) 2014 field campaign at Hyytiälä, Finland. In a case including heavily rimed snow followed by large aggregate snowflakes, we show that triple-frequency radar measurements provide a strong constraint on the PSD shape parameter, which can be estimated from an ensemble of retrievals; however, resolving variations in the PSD shape parameter has a limited impact on estimates of snowfall rate from radar. Particle density is more effectively constrained by the Doppler velocity than triple-frequency radar measurements, due to the strong dependence of particle fall speed on density. Due to the characteristic signatures of aggregate snowflakes, a third radar frequency is essential for effectively constraining the size of large aggregates. In a case featuring rime splintering, differences in the internal structures of aggregate snowflakes are revealed in the triple-frequency radar measurements. We compare retrievals assuming different aggregate snowflake models against in situ measurements at the surface and show significant uncertainties in radar retrievals of snow rate due to changes in the internal structure of aggregates. The importance of the PSD shape parameter and snowflake internal structure to triple-frequency radar retrievals of snow highlights that the processes by which ice particles interact may need to be better understood and parameterized before triple-frequency radar measurements can be used to constrain retrievals of ice particle morphology. [ABSTRACT FROM AUTHOR]

Creative thinking and empathy are crucial for everyday interactions and subjective well-being. This is emphasized by studies showing a reduction in these skills in populations where social interaction and subjective well-being are significantly compromised (e.g., depression). Anecdotal reports and recent studies suggest that a single administration of psilocybin can enhance such processes and could therefore be a potential treatment. However, it has yet to be assessed whether effects outlast acute intoxication. The present study aimed to assess the sub-acute effects of psilocybin on creative thinking, empathy, and well-being. Participants attending a psilocybin retreat completed tests of creative (convergent and divergent) thinking and empathy, and the satisfaction with life scale on three occasions: before ingesting psilocybin (N = 55), the morning after (N = 50), and seven days after (N = 22). Results indicated that psilocybin enhanced divergent thinking and emotional empathy the morning after use. Enhancements in convergent thinking, valence-specific emotional empathy, and well-being persisted seven days after use. Sub-acute changes in empathy correlated with changes in well-being. The study demonstrates that a single administration of psilocybin in a social setting may be associated with sub-acute enhancement of creative thinking, empathy, and subjective well-being. Future research should test whether these effects contribute to the therapeutic effects in clinical populations. [ABSTRACT FROM AUTHOR]

The accurate representation of ice particles is essential for both remotely-sensed estimates of cloud and precipitation and numerical models of the atmosphere. As it is typical in radar retrievals to assume that all snow is composed of unrimed aggregate snowflakes, both denser rimed snow and the mixed-phase cloud in which riming occurs may be under-diagnosed in retrievals, and therefore difficult to evaluate in weather and climate models. Recent experimental and numerical studies have yielded methods for using triple-frequency radar measurements to distinguish fractal aggregate snowflakes from more dense and homogeneous rimed particles. In this study we investigate which parameters of the particle size distribution (PSD) and morphology of ice particles are most important to the triple-frequency radar signature of snow, in order to carry out an optimal estimation retrieval using triple-frequency Doppler radar observations. We represent a range of ice particle morphologies using a fractal model for aggregate snowflakes and homogeneous spheroids to represent rimed graupel-like particles, and modulate the prefactor and exponent of the particles' mass-size relations with a density factor. We find that for both fractal particles and homogeneous spheroids the PSD shape has a greater influence on the triple-frequency radar signature than the density factor, and show that the PSD shape must be allowed to vary to adequately constrain a triple-frequency radar retrieval of snow. We then demonstrate a novel triple-frequency Doppler radar retrieval of three parameters of the PSD as well as particle density, and show that the estimated snow rate, PSD and bulk density compare well against in situ observations at the surface. In a case study of compact rimed snow, we find that triple-frequency radar measurements provide a strong constraint on the estimation of PSD shape, but a relatively weak constraint on particle density, which we find can be more directly estimated from the Doppler velocity due to the relation between particle density and fallspeed. Including variations in PSD shape as well as particle morphology allows for a better representation of the triple-frequency radar signatures of rimed and unrimed snow, and suggests the potential for making new insights into the interaction between particles during aggregation and riming mechanisms. However, we find that improved representation of the PSD shape has a limited impact on improved estimates of snow rate from radar. The importance of the PSD shape to triple-frequency radar retrievals of snow suggests that further work is needed to account for variations in PSD shape before triple-frequency radar measurements can be used to better constrain particle morphology. [ABSTRACT FROM AUTHOR]

• Administration of THC increased striatal glutamate concentrations. • THC decreased corticostriatal functional connectivity, indicating increased dopamine. • Average glutamate changes correlated strongly with functional connectivity changes. • Functional connectivity changes correlated with subjective effects. Abstract Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that Δ9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopamine, which is implicated in the rewarding effects of cannabis. Additional evidence suggests that THC may act indirectly on dopamine firing by modulating GABA and glutamate release. This double-blind, placebo-controlled study assessed the acute influence of two doses of THC on brain kinetics of glutamate, GABA, and dopamine, in relation to behavioral outcomes, by using magnetic resonance spectroscopy and functional magnetic resonance imaging. Twenty occasional cannabis users received acute doses of cannabis (300 µg/kg THC) and placebo, in one of two dose regimes (full dose and divided dose), during two separate testing days. Administration of THC increased striatal glutamate concentrations, and dopamine as indicated by a reduction in functional connectivity (FC) between the nucleus accumbens (NAc) and cortical areas. Alterations in glutamate and FC were dose dependent and evident in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with FC alterations. Additionally, THC induced changes in FC correlated with feelings of subjective high and decreased performance on an attention task. Taken together, this suggests that THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, which is associated with an increase in striatal glutamate. [ABSTRACT FROM AUTHOR]

Background: The effects of the glucocorticoid and progesterone receptor agonist megestrol on declarative memory, and the ability of phenytoin to block these effects, were assessed. Methods: Healthy volunteers received each medication combination (placebo and megestrol, phenytoin and megestrol, and placebo and placebo) using a randomized, crossover design. The Rey Auditory Verbal Learning Test assessed declarative memory. Results: Megestrol was associated with a significant reduction in declarative memory (p = 0.0008), which was attenuated by phenytoin, and was associated with significant cortisol suppression compared to placebo (p < 0.001). Conclusion: Changes in memory and cortisol suppression were found in healthy volunteers given megestrol. [ABSTRACT FROM AUTHOR]

Aiming at intervention, HIV antiretroviral therapy has been repurposed to treat murine cholangitis related to MMTV and provide clinically meaningful responses in PBC patients with HBRV [[2], [9]]. A betaretrovirus resembling mouse mammary tumor virus (MMTV) was first linked with human breast cancer over 50 years ago. It was originally referred to as human mammary tumor virus, and then the term human betaretrovirus (HBRV) was adopted when a similar agent was characterized in patients with primary biliary cholangitis (PBC), an autoimmune liver disease. [Extracted from the article]

A 31-year-old G5P1 patient with unremarkable past medical history at 29 weeks of gestation was diagnosed with a gigantic left frontotemporal brain mass. Initial clinical management as an inpatient achieved an improvement in the symptoms. The patient and surgical team agreed to schedule a cesarean delivery at 32 weeks of gestation if no neurological deterioration was observed. Intraoperative course with general endotracheal anesthesia and bilateral transversus abdominis plane block was uneventful and promoted efficient postoperative pain control. Seven days after delivery, the patient underwent craniotomy for brain tumor resection. This report describes the anesthetic management of a patient with an intracranial tumor during pregnancy. [ABSTRACT FROM AUTHOR]

Highlights • Existing traction equations predict values only for one mode of operation. • A unified traction algorithm is proposed for braked, towed, and powered wheels on dry sand. • The algorithm is developed using DROVE database. • The algorithm employs the ratio of contact pressure to cone index. • The new equation can be implemented in VTI and other off-road mobility models. Abstract Vehicle traction between the wheel and the ground surface is a critical design element for on-road and off-road mobility. Adequate traction in dry sand relates to the vehicle's ability to negotiate deserts, sand dunes, climb slopes, and ingress/egress along beaches. The existing traction equations predict values for only one mode of operation (braked, towed, or powered). In this article, we propose a unified algorithm for continuous prediction of traction over a range of braked, towed, and powered operations for wheels operating on sand. A database of laboratory and field records for wheeled vehicles, entitled Database Records for Off-road Vehicle Environments (DROVE), was used to develop the proposed algorithm. The algorithm employs the ratio of contact pressure to cone index as a primary variable to develop fitting parameters for a relationship between slip and traction. The performance of the algorithm is examined versus the measured data and is also compared against two alternative equations. The new equation showed higher correlation and lower error compared to the existing equations for powered wheels. The proposed equation can be readily implemented into off-road mobility models, eliminating the need for multiple traction equations for different modes of operation. [ABSTRACT FROM AUTHOR]

Here, we compare the outcomes of a criterion-referenced assessment of verbal behavior with those of an experimental verbal operant analyses to determine the extent to which the two evaluations yield data supporting similar conclusions. Specifically, we compared the results of functional analyses of verbal behavior with the verbal behavior outcomes measured on the Verbal Behavior Milestones Assessment and Placement Program (VB-MAPP; Sundberg, 2008). Five preschool to primary school-age children diagnosed with Autism Spectrum Disorder participated in this research. For each participant, we conducted the verbal operant analysis and VB-MAPP within seven days of one another. Results are presented in terms of relative response strength among four primary verbal operants: mands, tacts, echoics, and intraverbals. We found differing stimulus control ratios across these two measures of verbal behavior for each of the 5 participants. Implications for the evaluation and treatment of verbal behavior disorders are discussed within the context of construct validity. [ABSTRACT FROM AUTHOR]

The standard of care treatment for canine lymphoma is multi‐agent chemotherapy containing prednisolone, cyclophosphamide, vincristine and an anthracycline such as doxorubicin (CHOP) or epirubicin (CEOP). Lomustine, vincristine, procarbazine, and prednisone (LOPP) has been evaluated as a rescue, with encouraging results; however, resistance to vincristine is likely in patients relapsing on CHOP/CEOP, and this agent may enhance LOPP toxicity without improving efficacy. The aim of this study was to evaluate responses to a modified‐LOPP protocol that does not include vincristine (LPP) and is administered on a 21‐day cycle. Medical records of dogs with high‐grade multicentric lymphoma from 2012 to 2017 were reviewed. Dogs with relapsed lymphoma that received LPP as a rescue protocol were enrolled. Response, time from initiation to discontinuation (TTD) and toxicity of LPP were assessed. Forty‐one dogs were included. Twenty‐five dogs (61%) responded to LPP including 12 complete responses (CR) and 13 partial responses (PR). Responders had a significantly longer TTD (P < .001) compared to non‐responders with 84 days for CR and 58 days for PR. Neutropenia was documented in 20 dogs (57%): 12 grade I to II, 8 grade III to IV. Thrombocytopenia was infrequent (20%): 5 grade I to II, 2 grade III to IV. Twelve dogs developed gastrointestinal toxicity (30%): 10 grade I to II and 2 grade III. Nineteen dogs had elevated ALT (59%): 9 grade I to II, 10 grade III to IV. Treatment was discontinued due to toxicity in 8 dogs (19%). The LPP protocol shows acceptable efficacy and toxicity‐profile and minimizes in‐hospital procedures. [ABSTRACT FROM AUTHOR]

Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable. A pharmacokinetic/pharmacodynamic (PK/PD) APAP model has been built in order to understand the relationships between a panel of biomarkers and APAP dose. Visualization and statistical tools have been used to predict initial APAP dose and time since administration. Additionally, logistic regression analysis has been applied to histology data to provide a prediction of the probability of liver injury. [ABSTRACT FROM AUTHOR]

The current research investigated the effects of an avoidance contingency on the curriculum-based measures of three university students. Contemporary teaching practices in higher education promote the development of higher order skills, which are often contrasted with memorization. However, there is little empirical evidence to support educational practices at the university level. Three students in an introductory applied behavior analysis course participated in this project. Each class day throughout the semester, the participants took part in both a 1-min fluency drill and a daily quiz over the assigned readings. During baseline, these activities were independent of each other. The intervention consisted of making the quiz contingent on each student's fluency score. The number of vocabulary words identified by each participant increased after the avoidance contingency was applied, indicating that the prevention of daily quizzes served as a negative reinforcer to increase studying. Implications for the use and frequency of assessments in higher education are discussed. [ABSTRACT FROM AUTHOR]

The aims of this study were to report treatment outcomes for dogs with histiocytic sarcoma (HS) treated with both lomustine and epirubicin, and to report response rates to epirubicin as a rescue therapy in dogs previously treated with lomustine. Medical records of dogs with a diagnosis of HS that were treated with both lomustine and epirubicin were retrospectively evaluated. Of 29 dogs receiving epirubicin alternating with, or subsequent to lomustine treatment, including in a rescue setting, response to epirubicin could be assessed in 20 with an overall response rate (ORR) of 29% and biological response rate (BRR) of 71%. Median time to progression (TTP) in 12 of these 20 dogs in which it was assessable was 69 days (range: 40-125 days). For dogs treated in the rescue setting epirubicin specific ORR was 19% and BRR 63%. Median TTP in the 9 of these 16 dogs in which it was assessable was 62 days (range: 40-125 days). Median survival time for all dogs treated with both epirubicin and lomustine was 185 days (range: 27-500 days). Some dogs with HS respond to epirubicin and dogs treated with combinations of epirubicin and lomustine have modestly improved survival times compared with single agent studies, and similar to dogs with HS treated with alternating lomustine and doxorubicin. Single agent epirubicin is also a valid short term rescue therapy for canine HS. [ABSTRACT FROM AUTHOR]

Objective: Huntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real-life clinical diagnosis in HD.Method: A multivariate machine learning approach was applied to resting-state and structural magnetic resonance imaging scans from 19 premanifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years postscanning) and 21 healthy controls. A classification model was developed using cross-group comparisons between preHD and controls, and within the preHD group in relation to "estimated" and "actual" proximity to disease onset. Imaging measures were modeled individually, and combined, and permutation modeling robustly tested classification accuracy.Results: Classification performance for preHDs versus controls was greatest when all measures were combined. The resulting polymarker predicted converters with high accuracy, including those who were not expected to manifest in that time scale based on the currently adopted statistical models.Interpretation: We propose that a holistic multivariate machine learning treatment of brain abnormalities in the premanifest phase can be used to accurately identify those patients within 5 years of developing motor features of HD, with implications for prognostication and preclinical trials. Ann Neurol 2018;83:532-543. [ABSTRACT FROM AUTHOR]

During 2003-2013, fatality rates for oil and gas extraction workers decreased for all causes of death except those associated with fall events, which increased 2% annually during 2003-2013 (1). To better understand risk factors for these events, CDC examined fatal fall events in the oil and gas extraction industry during 2005-2014 using data from case investigations conducted by the Occupational Safety and Health Administration (OSHA). Sixty-three fatal falls were identified, accounting for 15% of all fatal events. Among fatal falls, 33 (52%) workers fell from a height of >30 feet (9 meters), and 22 (35%) fell from the derrick board, the elevated work platform located in the derrick (structure used to support machinery on a drilling rig). Fall fatalities occurred most frequently when drilling rigs were being assembled or disassembled at the well site (rigging up or rigging down) (14; 22%) or when workers were removing or inserting drill pipe into the wellbore (14; 22%). Measures that target derrickmen and workers engaged in assembling and disassembling drilling rigs (rigging up and down) could reduce falls in this industry. Companies should annually update their fall protection plans and ensure effective fall prevention programs are in place for workers at highest risk for falls, including providing trainings on proper use, fit, and inspection of personal protective equipment. [ABSTRACT FROM AUTHOR]

The article focuses on a research related to school governance and state takeovers in Detroit, Michigan and Memphis, Tennessee. Topics discussed include majority of public schools in New Orleans being brought under Recovery School District (RSD) following Hurricane Katrina's devastation of the state, Race to the Top (RTTT) program plans regarding lowest-achieving schools and Detroit schools involvement through the Education Achievement Authority (EAA).

Graphical abstract Highlights • Anion photoelectron spectrum of ZnBr− exhibits extended 280 ± 5 cm−1 neutral 2∑+vibrational progression. • ZnBr−1∑+ vibrational frequency is 120 ± cm−1. • ZnBr− bond dissociation energy is approximately 0.9 eV below neutral ZnBr. • ZnBr is less ionic than ZnF. Abstract Determination of the vibrational frequency of the ZnBr radical has been elusive, having previously been reported as 220 cm−1 and 318 cm−1 by different investigators. Recently, Burton and Ziurys reported a rotational spectrum of ZnBr from which they were able to estimate a harmonic frequency of 284 cm−1 and an anharmonicity of 1.0 cm−1. In this communication, we report a direct measurement of the vibrational spacing of ZnBr by anion photoelectron spectroscopy of ZnBr−. We determine the neutral vibrational frequency to be 280 ± 5 cm−1 (ω e x e = 1.5 ± 0.5 cm−1) and the anion vibrational frequency to be 120 ± 10 cm−1. In addition, we measure the electron affinity of the neutral radical to be 2.45 ± 0.06 eV, and determine that the bond dissociation energy of the anion is lower than that of the neutral by 0.91 ± 0.06 eV. [ABSTRACT FROM AUTHOR]

Modeling and simulation of vehicles in sand is critical for characterizing off-road mobility in arid and coastal regions. This paper presents improved algorithms for calculating sinkage ( z ) of wheeled vehicles operating on loose dry sand. The algorithms are developed based on 2737 tests conducted on sand with 23 different wheel configurations. The test results were collected from Database Records for Off-road Vehicle Environments (DROVE), a recently developed database of tests conducted with wheeled vehicles operating in loose dry sand. The study considers tire diameters from 36 to 124 cm with wheel loads of 0.19–36.12 kN. The proposed algorithms present a simple form of sinkage relationships, which only require the ratio of the wheel ground contact pressure and soil strength represented by cone index. The proposed models are compared against existing closed form solutions defined in the Vehicle Terrain Interface (VTI) model. Comparisons suggest that incorporating the proposed models into the VTI model can provide comparable predictive accuracy with simpler algorithms. In addition to simplicity, it is believed that the relationship between cone index (representing soil shear strength) and the contact pressure (representing the applied pressure to tire-soil interface) can better capture the physics of the problem being evaluated. [ABSTRACT FROM AUTHOR]

Mood is the changing expression of emotion and can be described as a spectrum. The outermost ends of this spectrum highlight two states, the lowest low, melancholia, and the highest high, mania. These mood extremes have been documented repeatedly in human history, being first systematically described by Hippocrates. Nineteenth century contemporaries Falret and Baillarger described two forms of an extreme mood disorder, with the validity and accuracy of both debated. Regardless, the concept of a cycling mood disease was accepted before the end of the 19th century. Kraepelin then described "manic depressive insanity" and presented his description of a full spectrum of mood dysfunction which could be exhibited through single episodes of mania or depression or a complement of many episodes of each. It was this concept which was incorporated into the first DSM and carried out until DSM-III, in which the description of episodic mood dysfunction was used to build a diagnosis of bipolar disorder. Criticism of this approach is explored through discussion of the bipolar spectrum concept and some recent examinations of the clinical validity of these DSM diagnoses are presented. The concept of bipolar disorder in children is also explored. [ABSTRACT FROM AUTHOR]

Background: International evidence suggests that dementia is under-diagnosed in the community and that General Practitioners (GPs) are often reluctant to engage to their fullest capability with patients who exhibit cognitive symptoms. This is potentially reflected by a lack of GP knowledge about the syndrome. However, it is also recognised that attitudes and confidence are important in relation to how and to what extent a GP approaches a person with dementia. This research sought to develop a reliable and valid measure of GPs attitudes and confidence towards dementia. Methods: The General Practitioner Attitudes and Confidence Scale for Dementia (GPACS-D) was developed via a four stage process, including initial content development, pretesting, pilot testing and psychometric evaluation, including Principal Component Analysis (PCA). Participants were recruited for pre-testing (n = 12), test-retest (n = 55), and dementia workshop pre-and post-education evaluation (n = 215). Results: The process of scale development and psychometric evaluation resulted in a 20-item measure of GP attitudes and confidence towards dementia, with 4 items removed due to poor reliability, low sensitivity, or lack of model fit. Among 55 respondents who completed the scale on two occasions with no intervening education, Kappa coefficient scores per item ranged from fair (n = 2, candidates for removal), moderate (n = 5), substantial (n = 15), and almost perfect (n = 2). A test of the sensitivity of item scores to change following dementia education among 215 GPs indicated that, with the exception of one item, all scale responses exhibited significant differences between pre-and post-workshop scores, indicating acceptable sensitivity. With one further item removed due to a low communality score, the final PCA undertaken with the remaining 20 items supports a four-component solution, which accounted for 51.9 % of the total variance. Conclusion: The GPACS-D provides a reliable and preliminarily valid measure of GP attitudes and confidence towards dementia. The scales provide useful information for medical educators and researchers who are interested in evaluating and intervening in GP perceptions of the syndrome and their capacity to provide effective care. [ABSTRACT FROM AUTHOR]