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Abstract Background Neurological disorders have had a substantial rise the last three decades, imposing substantial burdens on both patients and healthcare costs. Consequently, the demand for high-quality research has become crucial for exploring effective treatment options. However, current neurology research has some limitations in terms of transparency, reproducibility, and reporting bias. The adoption of reporting guidelines (RGs) and trial registration policies has been proven to address these issues and improve research quality in other medical disciplines. It is unclear the extent to which these policies are being endorsed by neurology journals. Therefore, our study aims to evaluate the publishing policies of top neurology journals regarding RGs and trial registration. Methods For this cross-sectional study, neurology journals were identified using the 2021 Scopus CiteScore Tool. The top 100 journals were listed and screened for eligibility for our study. In a masked, duplicate fashion, investigators extracted data on journal characteristics, policies on RGs, and policies on trial registration using information from each journal’s Instruction for Authors webpage. Additionally, investigators contacted journal editors to ensure information was current and accurate. No human participants were involved in this study. Our data collection and analyses were performed from December 14, 2022, to January 9, 2023. Results Of the 356 neurology journals identified, the top 100 were included into our sample. The five-year impact of these journals ranged from 50.844 to 2.226 (mean [SD], 7.82 [7.01]). Twenty-five (25.0%) journals did not require or recommend a single RG within their Instructions for Authors webpage, and a third (33.0%) did not require or recommend clinical trial registration. The most frequently mentioned RGs were CONSORT (64.6%), PRISMA (52.5%), and ARRIVE (53.1%). The least mentioned RG was QUOROM (1.0%), followed by MOOSE (9.0%), and SQUIRE (17.9%). Conclusions While many top neurology journals endorse the use of RGs and trial registries, there are still areas where their adoption can be improved. Addressing these shortcomings leads to further advancements in the field of neurology, resulting in higher-quality research and better outcomes for patients.

Abstract Background Assessment of eating disorders (ED) in youth relies heavily on self-report, yet persistent lack of recognition of the presence and/or seriousness of symptoms can be intrinsic to ED. This study examines the psychometric properties of a semi-structured interview, the parent version of the Eating Disorder Examination (PEDE), developed to systematically assess caregiver report of symptoms. Methods A multi-site, clinical sample of youth (N = 522; age range: 12 to 18 years) seeking treatment for anorexia nervosa (AN) and subsyndromal AN were assessed using the Eating Disorder Examination (EDE) for youth and the PEDE for collateral caregiver report. Results Internal consistencies of the four PEDE subscales were on par with established ranges for the EDE. Significant medium-sized correlations and poor to moderate levels of agreement were found between the corresponding subscales on each measure. For the PEDE, confirmatory factor analysis of the EDE four-factor model provided a poor fit; an exploratory factor analysis indicated that a 3-factor model better fits the PEDE. Conclusions Findings suggest that the PEDE has psychometric properties on par with the original EDE. The addition of the caregiver perspective may provide incremental information that can aid in the assessment of AN in youth. Future research is warranted to establish psychometric properties of the PEDE in broader transdiagnostic ED samples.

Abstract Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta‐analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: −0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse‐induced muscle atrophy. Although the meta‐analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse‐induced decline in either outcome measurement. Additional high‐quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.

Objective Our objective of this study was to analyse all oncological clinical trials using regorafenib to create a complete risk/benefit profile for the drug.Background Creating a novel chemotherapy is costly both in time and capital spent for drug manufacturers. To regenerate what they’ve spent, drug manufacturers may attempt to repurpose their medications for new indications via clinical trials. To fully understand the risk/benefits in comparison to a drug’s efficacy, a pooled analysis must be completed.Methods We screened PubMed, Embase, Cochrane (CENTRAL) and ClinicalTrials.gov for trials of regorafenib used to treat solid cancers. Next, we extracted median progression-free survival and overall survival in months, adverse event rates and objective response rate (ORR). Studies were deemed positive, negative or indeterminate based on their pre-specified endpoints and tolerability.Results 56 clinical trials were included in our final sample, with 4960 total participants across 13 indications. Most studies (44 of 56; 78.75%) were non-blinded, and a majority were non-randomised (41 of 56; 73.21%). Trials for colorectal cancer started out as positive but became more negative over time. Cumulative risk to patients increased over time while ORR stayed consistently low.Conclusions Our findings suggest that since regorafenib’s original Food and Drug Administration (FDA) approval, the risk profile for its original indication increased. The amount of non-randomised, single-arm trials in our sample size was concerning, indicating that higher quality research must be conducted. Our results propose that regorafenib’s efficacy and safety may be more impactful in cancers other than its FDA approvals.

Main problem: Chronic kidney disease (CKD) is a progressive condition that affects millions of people worldwide. A standardized core outcome set (COS) was developed for CKD by the International Consortium for Health Outcomes and Measurements in 2019. This study aims to evaluate the frequency of measurement for these outcomes before and after the publication of the COS. Methods: A literature search was done to gather the phase III/IV clinical trials evaluating chronic kidney disease through ClinicalTrials.gov. Data extraction of included studies was completed in a masked, duplicate fashion. The included studies were evaluated for characteristics such as survival, burden of disease, patient-reported health-related quality of life, and treatment modality-specific outcomes. Results: Our results showed that the majority of all COS domains were inadequately measured in CKD clinical trials before and after publication of the COS. Despite the increase in COS measurements following publication, the average percent of COS outcomes measured was less than 40 % per year even after four years. Conclusion: There is a notable deficiency in the complete measurement of COS among all domains both before and after COS publication. We suggest efforts be made to improve the adoption of consistent outcome measures that would benefit the growing population of patients affected by CKD.

Abstract Objective This study aims to evaluate published clinical trials of ramucirumab to assess the risk/benefit profile and burden over time for patients. Background The burden of oncologic drug development on patients paired with increasing clinical trial failure rates emphasizes the need for reform of drug development. Identifying and addressing patterns of excess burden can guide policy, ensure evidence‐based protections for trial participants, and improve medical decision‐making. Methods On May 25, 2023 a literature search was performed on Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for clinical trials using ramucirumab as monotherapy or in combination with other interventions for cancer treatment. Authors screened titles and abstracts for potential inclusion in a masked, duplicate fashion. Following data screening, data was extracted in a masked, duplicate fashion. Trials were classified as positive when meeting their primary endpoint and safety, negative or indeterminate. Results Ramucirumab was initially approved for gastric cancer but has since been tested in 20 cancers outside of its FDA approved indications. In our analysis of ramucirumab trials, there were a total of 10,936 participants and 10,303 adverse events reported. Gains in overall survival and progression‐free survival for patients were 1.5 and 1.2 months, respectively. FDA‐approved indications have reported more positive outcomes in comparison to off‐label indications. Conclusion We found that FDA‐approved indications for ramucirumab had better efficacy outcomes than non‐approved indications. However, a concerning number of adverse events were observed across all trials assessed. Participants in ramucirumab randomized controlled trials saw meager gains in overall survival when evaluated against a comparison group. Clinicians should carefully weigh the risks associated with ramucirumab therapy given its toxicity burden and poor survival gains.

Idealized test cases for the dynamical cores of atmospheric general circulation models are informative tools to assess the accuracy of the numerical designs and investigate the general characteristics of atmospheric motions. A new test case is introduced that is built upon a baroclinically unstable base state with an added orographic barrier. The topography is analytically prescribed and acts as a trigger of both baroclinic Rossby waves and inertia–gravity waves on a rotating, regular-sized planet. Both dry and idealized moist configurations are suggested. The latter utilizes the Kessler warm-rain precipitation scheme. The test case enhances the complexity of the existing test suite hierarchy and focuses on the impacts of two midlatitudinal mountain ridges on the circulation. Selected simulation examples from four dynamical cores are shown. These are the Spectral Element and Finite Volume dynamical cores, which are part of the National Center for Atmospheric Research (NCAR) Community Earth System Model (CESM), versions 2.1.3 and 2.2, and the Cubed-Sphere Finite Volume dynamical cores, which is new to CESM version 2.2. In addition, the Model for Prediction Across Scales (MPAS) is tested. The overall flow patterns agree well in the four dynamical cores, but the details can vary greatly. The examples highlight the broad palette of use cases for the test case and reveal physics–dynamics coupling issues.

This paper provides an overview of the United States (US) Department of Energy's (DOE's) Energy Exascale Earth System Model version 2 (E3SMv2) fully coupled regionally refined model (RRM) and documents the overall atmosphere, land, and river results from the Coupled Model Intercomparison Project 6 (CMIP6) DECK (Diagnosis, Evaluation, and Characterization of Klima) and historical simulations – a first-of-its-kind set of climate production simulations using RRM. The North American (NA) RRM (NARRM) is developed as the high-resolution configuration of E3SMv2 with the primary goal of more explicitly addressing DOE's mission needs regarding impacts to the US energy sector facing Earth system changes. The NARRM features finer horizontal resolution grids centered over NA, consisting of 25→100 km atmosphere and land, a 0.125∘ river-routing model, and 14→60 km ocean and sea ice. By design, the computational cost of NARRM is ∼3× of the uniform low-resolution (LR) model at 100 km but only ∼ 10 %–20 % of a globally uniform high-resolution model at 25 km. A novel hybrid time step strategy for the atmosphere is key for NARRM to achieve improved climate simulation fidelity within the high-resolution patch without sacrificing the overall global performance. The global climate, including climatology, time series, sensitivity, and feedback, is confirmed to be largely identical between NARRM and LR as quantified with typical climate metrics. Over the refined NA area, NARRM is generally superior to LR, including for precipitation and clouds over the contiguous US (CONUS), summertime marine stratocumulus clouds off the coast of California, liquid and ice phase clouds near the North Pole region, extratropical cyclones, and spatial variability in land hydrological processes. The improvements over land are related to the better-resolved topography in NARRM, whereas those over ocean are attributable to the improved air–sea interactions with finer grids for both atmosphere and ocean and sea ice. Some features appear insensitive to the resolution change analyzed here, for instance the diurnal propagation of organized mesoscale convective systems over CONUS and the warm-season land–atmosphere coupling at the southern Great Plains. In summary, our study presents a realistically efficient approach to leverage the fully coupled RRM framework for a standard Earth system model release and high-resolution climate production simulations.

We report on X-ray (NICER/NuSTAR/MAXI/Swift) and radio (MeerKAT) timing and spectroscopic analysis from a 3 month monitoring campaign in 2022 of a high-intensity outburst of the dipping neutron star low-mass X-ray binary 1A 1744−361. The 0.5–6.8 keV NICER X-ray hardness–intensity and color–color diagrams of the observations throughout the outburst suggest that 1A 1744−361 spent most of its outburst in an atoll-state, but we show that the source exhibited Z-state-like properties at the peak of the outburst, similar to a small sample of other atoll-state sources. A timing analysis with NICER data revealed several instances of an ≈8 Hz quasiperiodic oscillation (QPO; fractional rms amplitudes of ∼5%) around the peak of the outburst, the first from this source, which we connect to the normal branch QPOs seen in the Z-state. Our observations of 1A 1744−361 are fully consistent with the idea of the mass accretion rate being the main distinguishing parameter between atoll- and Z-states. Radio monitoring data by MeerKAT suggests that the source was at its radio-brightest during the outburst peak, and that the source transitioned from the “island” spectral state to the “banana” state within ∼3 days of the outburst onset, launching transient jet ejecta. The observations present the strongest evidence for radio flaring, including jet ejecta, during the island-to-banana spectral state transition at low accretion rates (atoll-state). The source also exhibited Fe xxv , Fe xxvi K α , and K β X-ray absorption lines, whose origins likely lie in an accretion disk atmosphere.

Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.

Abstract Background Inflammation and increases in inflammatory cytokines are common findings in psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Meta-analyses of studies that measured circulating cytokines have provided evidence of innate inflammation across all three disorders, with some overlap of inflammatory cytokines such as IL-6 and TNF-α. However, differences across disorders were also identified, including increased IL-4 in BD that suggest different immune mechanisms may be involved depending on the type of disorder present. Methods We sought to identify if the presence or absence of an affective disorder in first-episode psychotic (FEP) patients was associated with variations in cytokine production after stimulation of peripheral blood mononuclear cells (PBMC). 98 participants were recruited and grouped into healthy controls (n = 45) and first-episode psychosis patients (n = 53). Psychosis patients were further grouped by presence (AFF; n = 22) or lack (NON; n = 31) of an affective disorder. We cultured isolated PBMC from all participants for 48 h at 37 °C under four separate conditions; (1) culture media alone for baseline, or the following three stimulatory conditions: (2) 25 ng/mL lipopolysaccharide (LPS), (3) 10 ng/mL phytohemagglutinin (PHA), and (4) 125 ng/ml α-CD3 plus 250 ng/ml α-CD28. Supernatants collected at 48 h were analyzed using multiplex Luminex assay to identify differences in cytokine and chemokine production. Results from these assays were then correlated to patient clinical assessments for positive and negative symptoms common to psychotic disorders. Results We found that PBMC from affective FEP patients produced higher concentrations of cytokines associated with both innate and adaptive immunity after stimulation than non-affective FEP patients and healthy controls. More specifically, the AFF PBMC produced increased tumor necrosis fctor (TNF)-α, interleukin (IL)-1β, IL-6, and others associated with innate inflammation. PBMC from AFF also produced increased IL-4, IL-17, interferon (IFN)γ, and other cytokines associated with adaptive immune activation, depending on stimulation. Additionally, inflammatory cytokines that differed at rest and after LPS stimulation correlated with Scale for the Assessment of Negative Symptoms (SANS) scores. Conclusions Our findings suggest that immune dysfunction in affective psychosis may differ from that of primary psychotic disorders, and inflammation may be associated with increased negative symptoms. These findings could be helpful in determining clinical diagnosis after first psychotic episode.

The documentation of the change in the number and appearance of pigmented cutaneous lesions over time is critical to the early detection of skin cancers and may provide preliminary signals of efficacy in early-phase therapeutic prevention trials for melanoma. Despite substantial progress in computer-aided diagnosis of melanoma, automated methods to assess the evolution of lesions are relatively undeveloped. This report describes the development and narrow validation of mathematical algorithms to register nevi between sequential digital photographs of large areas of skin and to align images for improved detection and quantification of changes. Serial posterior truncal photographs from a pre-existing database were processed and analyzed by the software, and the results were evaluated by a panel of clinicians using a separate Extensible Markup Language‒based application. The software had a high sensitivity for the detection of cutaneous lesions as small as 2 mm. The software registered lesions accurately, with occasional errors at the edges of the images. In one pilot study with 17 patients, the use of the software enabled clinicians to identify new and/or enlarged lesions in 3‒11 additional patients versus the unregistered images. Automated quantification of size change performed similarly to that of human raters. These results support the further development and broader validation of this technique.

BackgroundThe purpose of our study is to assess the methodology of overlapping systematic reviews related to cemented vs uncemented hip hemiarthroplasties for the treatment of femoral neck fractures to find the study with the best evidence. Also, we assess the gaps in methodology and information to help with direction of future studies.MethodsA systematic search was conducted in September 2022 using Pubmed, Embase, and Cochrane Library. Clinical outcome data and characteristics of each study were extracted to see which treatment had better favorability. The outcomes and characteristics extracted from each study includes, first author, search date, publication journal and date, number of studies included, databases, level of evidence, software used, subgroup analyses that were conducted, and heterogeneity with the use of I2 statistics Methodological quality information was extracted from each study using four different methodologic scores (Oxford Levels of Evidence; Assessment of Multiple Systematic Reviews (AMSTAR); Quality of reporting of meta-analyses (QUROM); Oxman and Guyatt. After that, the Jadad decision algorithm was used to identify which studies in our sample contained the best available evidence. Finally, overlap of each systematic review was assessed using Corrected Covered Area (CCA) to look at redundancy and research waste among the systematic reviews published on the topic.ResultsAfter screening, 12 studies were included in our sample. For the Oxford Levels of Evidence, we found that all the studies were Level I evidence. For the QUORUM assessment, we had 1 study with the highest score of 18. Additionally, we did the Oxman and Guyatt assessment, where we found 4 studies with a maximum score of 6. Finally, we did an AMSTAR assessment and found 2 studies with a score of 9. After conducting the methodological scores; the authors determined that Li. L et al 2021 had the highest quality. In addition, it was found that the CCA found among the primary studies in each systematic review calculated to .22. Any CCA above .15 is considered "very high overlap".ConclusionsThe best available evidence suggests that Cemented HAs are better at preventing Prosthesis-related complications. Conversely, the best evidence also suggests that Cemented HA also results in longer operative time and increased intraoperative blood loss. When conducting future systematic reviews related to the topic, we ask that authors restrict conducting another systematic review until new evidence emerges so as not to confuse the clinical decision-making of physicians.

Abstract Background Measurement of cardiac structure and function from images (e.g. volumes, mass and derived parameters such as left ventricular (LV) ejection fraction [LVEF]) guides care for millions. This is best assessed using cardiovascular magnetic resonance (CMR), but image analysis is currently performed by individual clinicians, which introduces error. We sought to develop a machine learning algorithm for volumetric analysis of CMR images with demonstrably better precision than human analysis. Methods A fully automated machine learning algorithm was trained on 1923 scans (10 scanner models, 13 institutions, 9 clinical conditions, 60,000 contours) and used to segment the LV blood volume and myocardium. Performance was quantified by measuring precision on an independent multi-site validation dataset with multiple pathologies with n = 109 patients, scanned twice. This dataset was augmented with a further 1277 patients scanned as part of routine clinical care to allow qualitative assessment of generalization ability by identifying mis-segmentations. Machine learning algorithm (‘machine’) performance was compared to three clinicians (‘human’) and a commercial tool (cvi42, Circle Cardiovascular Imaging). Findings Machine analysis was quicker (20 s per patient) than human (13 min). Overall machine mis-segmentation rate was 1 in 479 images for the combined dataset, occurring mostly in rare pathologies not encountered in training. Without correcting these mis-segmentations, machine analysis had superior precision to three clinicians (e.g. scan-rescan coefficients of variation of human vs machine: LVEF 6.0% vs 4.2%, LV mass 4.8% vs. 3.6%; both P

Abstract Since summer 2021, the Radio Neutrino Observatory in Greenland (RNO-G) is searching for astrophysical neutrinos at energies $${>10}$$ > 10 PeV by detecting the radio emission from particle showers in the ice around Summit Station, Greenland. We present an extensive simulation study that shows how RNO-G will be able to measure the energy of such particle cascades, which will in turn be used to estimate the energy of the incoming neutrino that caused them. The location of the neutrino interaction is determined using the differences in arrival times between channels and the electric field of the radio signal is reconstructed using a novel approach based on Information Field Theory. Based on these properties, the shower energy can be estimated. We show that this method can achieve an uncertainty of 13% on the logarithm of the shower energy after modest quality cuts and estimate how this can constrain the energy of the neutrino. The method presented in this paper is applicable to all similar radio neutrino detectors, such as the proposed radio array of IceCube-Gen2.

Abstract Micron and nanometer size textured silicate glass surfaces are of interest in consumer electronics, photovoltaics, and biosensing applications. Typically, texturing glass surfaces requires applying a patterned mask or a pre-etching treatment (e.g. sandblasting) on the glass substrate, followed by a mask transferring or etching process using a fluoride-containing compound. The major challenges of such a process are the complexity and cost of masking, and the safety and environmental concerns around the usage and disposal of hydrofluoric acid. Here, we describe a template-free method to construct micron-sized and submicron-sized texture on isotropic glass surfaces in one step. The new texturing mechanisms are well supported by experimental data and peridynamic simulations. With this novel strategy, the etchant uses fluoride-free chemicals such as citric acid to texture silicate glass. Etchant concentration, etch temperature, time, and additives are the primary parameters that dictate the texturing process. Surface feature size and depth can be independently controlled by tuning the leaching and chemical polishing process. We hope this study can trigger more research on novel and more environmentally friendly texturing of isotropic materials.

Abstract Autism spectrum disorder (ASD) is a complex developmental disorder characterized by deficits in social interactions, communication, and stereotypical behaviors. Immune dysfunction is a common co-morbidity seen in ASD, with innate immune activation seen both in the brain and periphery. We previously identified significant differences in peripheral monocyte cytokine responses after stimulation with lipoteichoic acid (LTA) and lipopolysaccharide (LPS), which activate toll-like receptors (TLR)−2 and 4 respectively. However, an unbiased examination of monocyte gene expression in response to these stimulants had not yet been performed. To identify how TLR activation impacts gene expression in ASD monocytes, we isolated peripheral blood monocytes from 26 children diagnosed with autistic disorder (AD) or pervasive developmental disorder—not otherwise specified (PDDNOS) and 22 typically developing (TD) children and cultured them with LTA or LPS for 24 h, then performed RNA sequencing. Activation of both TLR2 and TLR4 induced expression of immune genes, with a subset that were differentially regulated in AD compared to TD samples. In response to LPS, monocytes from AD children showed a unique increase in KEGG pathways and GO terms that include key immune regulator genes. In contrast, monocytes from TD children showed a consistent decrease in expression of genes associated with translation in response to TLR stimulation. This decrease was not observed in AD or PDDNOS monocytes, suggesting a failure to properly downregulate a prolonged immune response in monocytes from children with ASD. As monocytes are involved in early orchestration of the immune response, our findings will help elucidate the mechanisms regulating immune dysfunction in ASD.

Introduction: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. Methods: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. Results: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: −70.86 to −40.57, p

Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-β1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.

Tree rings are a crucial archive for Common Era climate reconstructions, but the degree to which methodological decisions influence outcomes is not well known. Here, the authors show how different approaches taken by 15 different groups influence the ensemble temperature reconstruction from the same data.

Atmospheric gravity waves (GWs) play an important role in atmospheric dynamics but accurately representing them in general circulation models (GCMs) is challenging. This is especially true for orographic GWs generated by wind flow over small mountainous islands in the Southern Ocean. Currently, these islands lie in the “grey zone” of global model resolution, where they are neither fully resolved nor fully parameterised. It is expected that as GCMs approach the spatial resolution of current high-resolution local-area models, small-island GW sources may be resolved without the need for parameterisations. But how realistic are the resolved GWs in these high-resolution simulations compared to observations? Here, we test a high-resolution (1.5 km horizontal grid, 118 vertical levels) local-area configuration of the Met Office Unified Model over the mountainous island of South Georgia (54∘ S, 36∘ W), running without GW parameterisations. The island's orography is well resolved in the model, and real-time boundary conditions are used for two time periods during July 2013 and June–July 2015. We compare simulated GWs in the model to coincident 3-D satellite observations from the Atmospheric Infrared Sounder (AIRS) on board Aqua. By carefully sampling the model using the AIRS resolution and measurement footprints (denoted as model sampled as AIRS hereafter), we present the first like-for-like comparison of simulated and observed 3-D GW amplitudes, wavelengths and directional GW momentum flux (GWMF) over the island using a 3-D S-transform method. We find that the timing, magnitude and direction of simulated GWMF over South Georgia are in good general agreement with observations, once the AIRS sampling and resolution are applied to the model. Area-averaged zonal GWMF during these 2 months is westward at around 5.3 and 5.6 mPa in AIRS and model sampled as AIRS datasets respectively, but values directly over the island can exceed 50 mPa. However, up to 35 % of the total GWMF in AIRS is actually found upwind of the island compared to only 17 % in the model sampled as AIRS, suggesting that non-orographic GWs observed by AIRS may be underestimated in our model configuration. Meridional GWMF results show a small northward bias (∼20 %) in the model sampled as AIRS that may correspond to a southward wind bias compared to coincident radiosonde measurements. Finally, we present one example of large-amplitude (T′≈15–20 K at 45 km altitude) GWs at short horizontal wavelengths (λH≈30–40 km) directly over the island in AIRS measurements that show excellent agreement with the model sampled as AIRS. This suggests that orographic GWs in the full-resolution model with T′≈45 K and λH≈30–40 km can occur in reality. Our study demonstrates that not only can high-resolution local-area models simulate realistic stratospheric GWs over small mountainous islands but the application of satellite sampling and resolution to these models can also be a highly effective method for their validation.

Abstract Background Malnutrition, sarcopenia and cachexia are clinical wasting syndromes characterised by muscle loss. Systematic monitoring by body composition assessment (BCA) is recommended for the diagnosis, treatment and monitoring of the syndrome(s). This study investigated practices, competency, and attitudes of Australian dietitians regarding BCA, to inform a local implementation process. Methods Applying the Action cycle in the Knowledge to Action framework, surveys were distributed to the 26 dietitians of an 800-bed tertiary hospital. The survey assessed barriers and enablers to performing routine BCA in clinical care. Results were categorised using the Theoretical Domains Framework (TDF) and suitable interventions mapped using the Behaviour Change Wheel. Results Twenty-two dietitians (84.6%) completed the survey. Barriers to BCA were identified in all TDF domains, particularly in Knowledge, Skills, Social/professional role and identity, Beliefs about capabilities, and Environmental context and resources. Enablers existed in domains of: Skills; Beliefs about consequences; Goals; Environmental context and resources; Social influences; Intentions; Optimism; Reinforcement. Conclusions This study showed that hospital dietitians experience individual, team, and organisational barriers to adopt BCAs in clinical practice. We were able to formulate targeted implementation strategies to overcome these barriers to assist BCA adoption into routine practice.

Abstract Liver receptor homolog-1 (NR5A2) is expressed specifically in granulosa cells of developing ovarian follicles where it regulates the late stages of follicle development and ovulation. To establish its effects earlier in the trajectory of follicular development, NR5A2 was depleted from granulosa cells of murine primordial and primary follicles. Follicle populations were enumerated in neonates at postnatal day 4 (PND4) coinciding with the end of the formation of the primordial follicle pool. The frequency of primordial follicles in PND4 conditional knockout (cKO) ovaries was greater and primary follicles were substantially fewer relative to control (CON) counterparts. Ten-day in vitro culture of PND4 ovaries recapitulated in vivo findings and indicated that CON mice developed primary follicles in the ovarian medulla to a greater extent than did cKO animals. Two subsets of primordial follicles were observed in wildtype ovaries: one that expressed NR5A2 and the second in which the transcript was absent. Neither expressed the mitotic marker. KI-67, indicating their developmental quiescence. RNA sequencing on PND4 demonstrated that loss of NR5A2 induced changes in 432 transcripts, including quiescence markers, inhibitors of follicle activation, and regulators of cellular migration and epithelial-to-mesenchymal transition. These experiments suggest that NR5A2 expression poises primordial follicles for entry into the developing pool.

We present new radial velocity measurements from the Magellan and the Anglo-Australian Telescopes for 175 previously known and 121 newly confirmed globular clusters (GCs) around NGC 5128, the nearest accessible massive early-type galaxy at D = 3.8 Mpc. Remarkably, 28 of these newly confirmed GCs are at projected radii $\gt 50^{\prime} $ (≳54 kpc), extending to ∼130 kpc, in the outer halo where few GCs had been confirmed in previous work. We identify several subsets of GCs that spatially trace halo substructures that are visible in red giant branch star maps of the galaxy. In some cases, these subsets of GCs are kinematically cold, and may be directly associated with and originate from these specific stellar substructures. From a combined kinematic sample of 645 GCs, we see evidence for coherent rotation at all radii, with a higher rotation amplitude for the metal-rich GC subpopulation. Using the tracer mass estimator, we measure a total enclosed mass of 2.5 ± 0.3 × 10 ^12 M _⊙ within ∼120 kpc, an estimate that will be sharpened with forthcoming dynamical modeling. The combined power of stellar mapping and GC kinematics makes NGC 5128 an ongoing keystone for understanding galaxy assembly at mass scales inaccessible in the Local Group.

Stratospheric volcanic eruptions have had significant impacts on the radiation budget, atmospheric and surface temperatures, precipitation and regional weather patterns, resulting in global climatic changes. The changes associated with such eruptions most commonly result in cooling during several years after events. This study aimed to reveal eco-physiological response of larch trees from northeastern Yakutia (YAK), eastern Taimyr (TAY) and Altai (ALT) regions to climatic anomalies after major volcanic eruptions CE 535, 540, 1257, 1641, 1815 and 1991 using new multiple tree-ring parameters: tree-ring width (TRW), maximum latewood density (MXD), cell wall thicknesses (CWT), δ13C and δ18O in tree-ring cellulose. This investigation showed that TRW, CWT, MXD and δ18O chronologies recorded temperature signal, while information about precipitation and vapor pressure deficit was captured by δ13C chronologies. Sunshine duration was well recorded in δ18O from YAK and ALT. Tree-ring parameters recorded cold, wet and cloudy summer anomalies during the 6th and 13th centuries. However, significant summer anomalies after Tambora (1815) and Pinatubo (1991) eruptions were not captured by any tree-ring parameters

Abstract Objective To examine the correlation between eating disorder (ED) symptoms and borderline personality disorder (BPD) traits in a sample of adolescents with eating disorders. Method There were 168 participants (Mage = 16.0 years; SD = 1.16) with a diagnosis of anorexia nervosa (AN) or Eating Disorder Not Otherwise Specified—AN type. Eating Disorder Examination (EDE) and the Borderline Personality Questionnaire (BPQ) were used to assess ED symptoms and BPD traits. Results A total of 10 participants (6.6%) scored above the clinical cut‐off for a likely diagnosis of BPD. A positive correlation was observed between BPQ total score and EDE global (rs = 0.64, p

Objective: Inhibitory control training (ICT) has shown promise for improving health behaviours, however, less is known about its mediators of effectiveness. The current paper reports whether ICT reduces smoking-related outcomes such as craving and nicotine dependence, increases motivation to quit and whether reductions in smoking or craving are mediated by response inhibition or a devaluation of smoking stimuli.Method: Adult smokers (minimum 10 cigarettes per day; N = 107, Mage = 46.15 years, 57 female) were randomly allocated to receive 14 days of smoking-specific ICT (named INST; a go/no-go task where participants were trained to not respond to smoking stimuli) or active control training (participants inhibited responding toward neutral stimuli). Participants were followed up to 3-months post-intervention. This trial was preregistered (Australian and New Zealand Clinical Trials Registry ID: ACTRN12617000252314; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370204).Results: There were no significant differences between ICT and active control training groups. Specifically, participants in both groups showed significant reductions in craving, nicotine dependence, motivation and a devaluation (reduced evaluation) of smoking-stimuli up to 3-months follow-up compared to baseline. Inhibition and devaluation of smoking stimuli did not act as mediators. Devaluation of smoking stimuli was an independent predictor of smoking and craving at follow-up.Conclusion: Inhibitory control training (ICT) was no more effective at reducing smoking-related outcomes compared to the active control group, however, significant improvements in craving, dependence indicators and evaluation of smoking stimuli were observed across both groups. A return to basic experimental research may be required to understand the most effective ICT approach to support smoking cessation.

Melanocytes reside within the basal epidermis of human skin, and function to protect the skin from ultraviolet light through the production of melanin. Prolonged exposure of the skin to UV light can induce irreparable DNA damage and drive cells into senescence, a sustained cell cycle arrest that prevents the propagation of this damage. Senescent cells can also be detrimental and contribute to skin ageing phenotypes through their senescence-associated secretory phenotype. Senescent cells can act in both an autocrine and paracrine manner to produce widespread tissue inflammation and skin ageing. Recently, melanocytes have been identified as the main senescent cell population within the epidermis and have been linked to a variety of skin ageing phenotypes, such as epidermal thinning and the presence of wrinkles. However, the literature surrounding melanocyte senescence is limited and tends to focus on the role of senescence in the prevention of melanoma. Therefore, this review aims to explore the current understanding of the contribution of senescent melanocytes to human skin ageing.

This study aimed to investigate the immediate and continual perturbation to the gut microbiota of offspring in the weeks post-weaning and how these may be modulated by treating pregnant C57BL/6J dams with antibiotics (ABX). We used a broad-spectrum antibiotic cocktail consisting of ampicillin 1 mg/mL, neomycin 1 mg/mL, and vancomycin 0.5 mg/mL, or vancomycin 0.5 mg/mL alone, administered ad-lib orally to dams via drinking water during gestation and stopped after delivery. We analyzed the gut microbiota of offspring, cytokine profiles in circulation, and the brain to determine if there was evidence of a gut-immune-brain connection. Computationally predicted metabolic pathways were calculated from 16s rRNA sequencing data. ABX treatment can negatively affect the gut microbiota, including reduced diversity, altered metabolic activity, and immune function. We show that the maternal ABX-treatment continues to alter the offspring’s gut microbiota diversity, composition, and metabolic pathways after weaning, with the most significant differences evident in 5-week-olds as opposed to 4-week-olds. Lower levels of chemokines and inflammatory cytokines, such as interleukin (IL)-1α and IL-2, are also seen in the periphery and brains of offspring, respectively. In conclusion, this study shows maternal antibiotic administration alters gut microbiome profiles in offspring, which undergoes a continuous transformation, from week to week, at an early age after weaning.

Background Impaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype‐positive, left ventricular hypertrophy‐negative). Methods and Results A single center, case‐control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre‐phenotypic features of HCM. Individuals with genotype‐positive, left ventricular hypertrophy‐negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH‐fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype‐positive, left ventricular hypertrophy‐negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m2, P=0.03), lower left ventricular end‐systolic volume (21.0±6.9 versus 26.7±6.2 mm/m2, P≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P=0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls (P=0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P=0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P=

Stratospheric volcanic eruptions have far-reaching impacts on global climate and society. Tree rings can provide valuable climatic information on these impacts across different spatial and temporal scales. To detect temperature and hydroclimatic changes after strong stratospheric Common Era (CE) volcanic eruptions for the last 1500 years (535 CE unknown, 540 CE unknown, 1257 CE Samalas, 1640 CE Parker, 1815 CE Tambora, and 1991 CE Pinatubo), we measured and analyzed tree-ring width (TRW), maximum latewood density (MXD), cell wall thickness (CWT), and δ13C and δ18O in tree-ring cellulose chronologies of climate-sensitive larch trees from three different Siberian regions (northeastern Yakutia – YAK, eastern Taimyr – TAY, and Russian Altai – ALT). All tree-ring proxies proved to encode a significant and specific climatic signal of the growing season. Our findings suggest that TRW, MXD, and CWT show strong negative summer air temperature anomalies in 536, 541–542, and 1258–1259 at all studied regions. Based on δ13C, 536 was extremely humid at YAK, as was 537–538 in TAY. No extreme hydroclimatic anomalies occurred in Siberia after the volcanic eruptions in 1640, 1815, and 1991, except for 1817 at ALT. The signal stored in δ18O indicated significantly lower summer sunshine duration in 542 and 1258–1259 at YAK and 536 at ALT. Our results show that trees growing at YAK and ALT mainly responded the first year after the eruptions, whereas at TAY, the growth response occurred after 2 years. The fact that differences exist in climate responses to volcanic eruptions – both in space and time – underlines the added value of a multiple tree-ring proxy assessment. As such, the various indicators used clearly help to provide a more realistic picture of the impact of volcanic eruption on past climate dynamics, which is fundamental for an improved understanding of climate dynamics, but also for the validation of global climate models.

Abstract Background Atypical anorexia nervosa (AN) has received minimal empirical attention regarding effective diagnosis and treatment. Family-based treatment (FBT) might be a promising treatment for atypical AN, yet it is unclear as to what adaptations are needed to the current manualized FBT for AN model. The objective of the current study was to identify how FBT practitioners applied FBT for atypical AN for adolescents in their clinical practice, and if there were any implementation challenges and adaptations to the model for this population. Methods The current study employed fundamental qualitative description, with the aim of capturing practitioners’ reflections on working with adolescents with atypical AN in clinical practice. A purposeful sample of practitioners with training in FBT were recruited and each participant completed an individual, semi-structured interview. Data was analyzed using conventional content analysis. Results A total of 23 practitioners participated in this study. The results indicate that practitioners maintained some fidelity to manualized FBT in treating atypical AN, but they differed in their discussions around target weights, what constitutes weight restoration, and the dosage for FBT phases. Salient practice challenges included operationalizing the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition (DSM-5) definition of atypical AN, identifying a ‘goal weight’ for adolescents and activating parents to take charge of the re-nourishment process. Conclusions The results of this qualitative study demonstrate practitioner reflections on the delivery and adaptations of FBT for adolescents with atypical AN. These reflections highlight the need to establish the delivery of coherent and consistent treatment and messaging with patients and families. Further, practitioners’ reflections highlight common strategies to increase the sense of urgency in parents to support their child with atypical AN.

This study investigated the effect of antibiotics administered to pregnant dams on offspring gut microbiome composition and metabolic capabilities, and how these changes in the microbiota may influence their immune responses in both the periphery and the brain. We orally administered a broad-spectrum antibiotic (ABX) cocktail consisting of vancomycin 0.5 mg/mL, ampicillin 1 mg/mL, and neomycin 1 mg/mL to pregnant dams during late gestation through birth. Bacterial DNA was extracted from offspring fecal samples, and 16S ribosomal RNA gene was sequenced by Illumina, followed by analysis of gut microbiota composition and PICRUSt prediction. Serum and brain tissue cytokine levels were analyzed by Luminex. Our results indicate that the ABX-cocktail led to significant diversity and taxonomic changes to the offspring’s gut microbiome. In addition, the predicted KEGG and MetaCyc pathways were significantly altered in the offspring. Finally, there were decreased innate inflammatory cytokines and chemokines and interleukin (IL)-17 seen in the brains of ABX-cocktail offspring in response to lipopolysaccharide (LPS) immune challenge. Our results suggest that maternal ABX can produce long-lasting effects on the gut microbiome and neuroimmune responses of offspring. These findings support the role of the early microbiome in the development of offspring gastrointestinal and immune systems.

Abstract Background Smoking is one of the leading preventable causes of illness and premature death worldwide. Despite a variety of effective treatments, relapse rates remain high, and novel, innovative interventions are needed in order to reduce the global prevalence of smoking. Research has indicated that deficits in the ability to inhibit a response (referred to as response inhibition) is a predictor of relapse and subsequently, targeting this potentially modifiable risk factor may lead to improvements in smoking outcomes. Indeed, in recent years, stimulus-specific response inhibition training has emerged as a potentially efficacious intervention to reduce unwanted/unhealthy behaviours such as alcohol and unhealthy food consumption. As such, the present trial is the first to evaluate the real-world efficacy of response inhibition smoking training (INST) in a sample of adult heavy smokers. Methods/design This randomised controlled trial will recruit nicotine dependent smokers aged between 18 and 60 using social media and advertisements in Victoria, Australia. The sample target was 150 to account for drop out and non-adherence. Once informed consent has been obtained, participants complete a range of baseline measures during a face to face interview. Participants are randomly allocated to one of two online training conditions: an intervention training group (INST), which requires participants to exercise response inhibition towards smoking-related stimuli; or an active control group, which requires participants to exercise response inhibition towards household items and does not include any smoking-related stimuli. They complete the first training session during the interview to ensure the training protocol is clear. Both groups are instructed to complete a further 13 training sessions (1 per day) at home on their computer and follow-up phone calls will be conducted at three time points: post-intervention, one-month and three months. The primary outcomes are: a) rates of smoking cessation and; b) reduction in the quantity of average daily smoking at post-intervention, one and three months follow-up. Discussion There is a pressing need to develop novel and innovative smoking interventions. If proven to be effective, INST could make a highly cost-effective contribution to improvements in smoking intervention outcomes. Trial registration The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry 17th February 2017. Trial ID: ACTRN12617000252314.

Increased innate immune activation and inflammation are common findings in psychotic and affective (mood) disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), including increased numbers and activation of monocytes and macrophages. These findings often differ depending on the disorder, for example, we previously found increases in circulating inflammatory cytokines associated with monocytes and macrophages in SCZ, while BD had increases in anti-inflammatory cytokines. Despite these differences, few studies have specifically compared immune dysfunction in affective versus non-affective psychotic disorders and none have compared functional monocyte responses across these disorders. To address this, we recruited 25 first episode psychosis (FEP) patients and 23 healthy controls (HC). FEP patients were further grouped based on the presence (AFF) or absence (NON) of mood disorder. We isolated peripheral blood mononuclear cells and cultured them for 1 week with M-CSF to obtain monocyte-derived macrophages. These cells were then stimulated for 24 h to skew them to inflammatory and alternative phenotypes, in order to identify differences in these responses. Following stimulation with LPS and LPS plus IFNγ, we found that macrophages from the NON-group had diminished inflammatory responses compared to both HC and AFF groups. Interestingly, when skewing macrophages to an alternative phenotype using LPS plus IL-4, the AFF macrophages increased production of inflammatory cytokines. Receiver operating curve analysis showed predictive power of inflammatory cytokine concentrations after LPS stimulation in the AFF group versus NON-group. Our results suggest dysfunctional monocyte responses in both affective and non-affective psychotic disorder, with varying types of immune dysfunction depending on the presence or absence of a mood component.

Despite a focus on physical and cognitive outcomes, stroke survivors are also impacted by emotional and mental health challenges. Additionally, their caregivers may experience decreased well-being due to increased burden and role adjustment. A small body of literature characterizes this experience as a form of grief and loss. This study seeks to explore experiences of grief and loss reported by stroke survivors and caregivers, using Holbrook’s 4-stage bereavement model. This cross-sectional, qualitative study was conducted among adult stroke survivors (n = 9) and their spousal caregivers (n = 5). Focus groups on experiences of recent hospitalizations and transitions home were transcribed, coded, and thematic analysis was conducted, identifying a major theme of loss. Data were reanalyzed guided by Holbrook’s model. Common themes were losses and changes experienced by patients/caregivers, disbelief, and lack of understanding. Subthemes of denial and confusion were present. Less prevalent themes were loss of existing support systems and silver lining. Stroke survivors and caregivers experienced a range of negative emotions, impacting behaviors, self-perception, roles, and social support. Awareness of these issues can improve practice with those affected by stroke.

The prevalence of autism spectrum disorder (ASD) has starkly increased, instigating research into risk factors for ASD. This research has identified immune risk factors for ASD, along with evidence of immune dysfunction and excess inflammation frequently experienced by autistic individuals. Increased innate inflammatory cytokines, including interleukin (IL)-6, are seen repeatedly in ASD; however, the origin of excess IL-6 in ASD has not been identified. Here we explore specific responses of circulating monocytes from autistic children. We isolated CD14+ monocytes from whole blood and stimulated them for 24 h under three conditions: media alone, lipoteichoic acid to activate TLR2, and lipopolysaccharide to activate TLR4. We then measured secreted cytokine concentrations in cellular supernatant using a human multiplex bead immunoassay. We found that after TLR4 activation, CD14+ monocytes from autistic children produce increased IL-6 compared to monocytes from children with typical development. IL-6 concentration also correlated with worsening restrictive and repetitive behaviors. These findings suggest dysfunctional activation of myeloid cells, and may indicate that other cells of this lineage, including macrophages, and microglia in the brain, might have a similar dysfunction. Further research on myeloid cells in ASD is warranted.

Selenium (Se)-deficient soils necessitate supplementation of this mineral to the diet of forage-grazing cattle. Functionally, Se is incorporated into selenoproteins, some of which function as important antioxidants. We have previously shown that the source of supplemental Se; inorganic (sodium selenite or sodium selenate; ISe), organic (selenomethionine or selenocysteine; OSe) or 1:1 mix of ISe and OSe (MIX), provided to Angus-cross cows affects concentrations of progesterone (P4) during the early luteal phase of the estrous cycle. In this study, we sought to investigate (1) the effect of form of Se on the expression of mRNA encoding selenoproteins in the corpus luteum (CL), and (2) whether this previously reported MIX-induced increase in P4 is the result of increased luteal expression of key steroidogenic transcripts. Following a Se depletion and repletion regimen, 3-year-old, non-lactating, Angus- cross cows were supplemented with either ISe as the industry standard, or MIX for at least 90 days, with the CL then retrieved on Day 7 post-estrus. Half of each CL was used for analysis of targeted mRNA transcripts and the remainder was dissociated for culture with select agonists. The expression of three selenoprotein transcripts and one selenoprotein P receptor was increased (p < 0.05), with an additional five transcripts tending to be increased (p < 0.10), in cows supplemented with MIX versus ISe. In cultures of luteal cells, hCG-induced increases in P4 (p < 0.05) were observed in CL obtained from ISe-supplemented cows. The abundance of steroidogenic transcripts in the CL was not affected by the form of Se, however, the abundance of mRNA encoding 2 key transcripts regulating cholesterol availability (Ldlr and Hsl) was increased (p < 0.05) in MIX-supplemented cows. Overall, the form of Se provided to cows is reported to affect the expression of mRNA encoding several selenoproteins in the CL, and that the form of Se-induced effects on luteal production of P4 appears to be the result of changes in cholesterol availability rather than a direct effect on the expression of steroidogenic enzymes within the CL.

ObjectiveIncorporating consumer perspectives is an important but often overlooked opportunity to optimize treatment engagement and outcomes for adolescents with eating disorders. This study explored the experience of care of adolescents and their parents at a multidisciplinary specialist eating disorders service providing family-based treatment (FBT) as first-line treatment.MethodEighty-five adolescents and 145 parents who completed FBT at the service between 2013 and 2015 were surveyed in 2017 about their experience of care. A study-designed survey asked respondents to rate on Likert scales their experience of service access, intake assessment, education, support, interactions with the treatment team, recovery, and the discharge process. Open-ended comments on helpful and unhelpful aspects of the service provided further context on the ratings.ResultsOverall families were very positive about their experience, particularly in regard to assessment, education, interactions with the team, and achieving physical health. Although parents tended to be more satisfied, adolescents also held the service in high regard. Some areas were identified that could be improved, including treatment delays, carer support, therapeutic alliance, and preparation for discharge.ConclusionsSurveying families about their experience of care provides an important opportunity to identify service strengths as well as services gaps. The results indicated several areas that specialist eating disorder services could focus on to ensure that the services provided, including FBT, fully meet the needs of families and optimize adolescents’ treatment experiences.