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The use of deep learning (DL) is steadily gaining traction in scientific challenges such as cancer research. Advances in enhanced data generation, machine learning algorithms, and compute infrastructure have led to an acceleration in the use of deep learning in various domains of cancer research such as drug response problems. In our study, we explored tree-based models to improve the accuracy of a single drug response model and demonstrate that tree-based models such as XGBoost (eXtreme Gradient Boosting) have advantages over deep learning models, such as a convolutional neural network (CNN), for single drug response problems. However, comparing models is not a trivial task. To make training and comparing CNNs and XGBoost more accessible to users, we developed an open-source library called UNNT (A novel Utility for comparing Neural Net and Tree-based models). The case studies, in this manuscript, focus on cancer drug response datasets however the application can be used on datasets from other domains, such as chemistry.

Participatory research approaches hold potential to better understand society through valuing lived experience. Formula feeding babies is routinely stigmatised in the UK, despite inadequate support to facilitate breastfeeding. Our community science project investigated the safety of powdered infant formula preparation in the home through the completion of an at-home experiment and a research diary with closed and open questions ( n = 151). To add validity to the interpretation of open text data in research diaries, a community analysis group of five formula-feeding mothers was established. The community analysts undertook inductive thematic analysis through a series of analysis group meetings focused around data extracts, contributed to the study’s empirical outputs and this methodological output, meeting 23 times over a nine-month period. Detailed notes were taken during meetings and the methodological elements of these were thematically analysed with the community analysts to produce this article, with extracts from the academic researchers’ field notes added where relevant. The overarching themes, presenting both positive experiences and areas for improvement, focused on: (i) clarity of expectations and the impact this had on community analysts’ confidence, (ii) the stigmatising topic area and how this was managed by the facilitators, and (iii) feeling valued, in relation to honoraria, inclusion in outputs and community analysts coming to recognise their own expertise. Furthermore, the community analysts co-produced recommendations for including community analysts in future research. It provides guidance on how this can be appropriately costed for and supported by funding bodies and research teams, as well as providing guidance on recruitment and chairing meetings. We hope that this article can provide valuable input into how to involve the community more inclusively as research partners in qualitative analysis related to stigmatised topics.

Abstract Formula fed infants experience gastrointestinal infections at higher rates than breastfed infants, due in part to bacteria in powdered infant formula (PIF) and bacterial contamination of infant feeding equipment. The United Kingdom National Health Service (UK NHS) has adopted the World Health Organization recommendation that water used to reconstitute PIF is ≥70°C to eliminate bacteria. We used community science methods to co‐design an at home experiment and online questionnaire (‘research diary’) to explore the safety of PIF preparation compared to UK NHS guidelines. 200 UK‐based parents of infants aged ≤12 months were recruited; 151 provided data on PIF preparation, and 143 were included in the analysis of water temperatures used to reconstitute PIF. Only 14.9% (n = 11) of 74 PIF preparation machines produced a water temperature of ≥70°C compared with 78.3% (n = 54) of 69 kettle users (p

Abstract Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell is mediated through the binding of the SARS-CoV-2 Spike protein via the receptor binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2). Identifying compounds that inhibit Spike-ACE2 binding would be a promising and safe antiviral approach against COVID-19. Methods In this study, we used a BSL-2 compatible replication-competent vesicular stomatitis virus (VSV) expressing Spike protein of SARS-CoV-2 with eGFP reporter system (VSV-eGFP-SARS-CoV-2) in a recombinant permissive cell system for high-throughput screening of viral entry blockers. The SARS-CoV-2 permissive reporter system encompasses cells that stably express hACE2-tagged cerulean and H2B tagged with mCherry, as a marker of nuclear condensation, which also enables imaging of fused cells among infected EGFP positive cells and could provide real-time information on syncytia formation. Results A limited high-throughput screening identified six natural products that markedly inhibited VSV-eGFP-SARS-CoV-2 with minimum toxicity. Further studies of Spike-S1 binding using the permissive cells showed Scillaren A and 17-Aminodemethoxygeldanamycin could inhibit S1 binding to ACE2 among the six leads. A real-time imaging revealed delayed inhibition of syncytia by Scillaren A, Proscillaridin, Acetoxycycloheximide and complete inhibition by Didemnin B indicating that the assay is a reliable platform for any image-based drug screening. Conclusion A BSL-2 compatible assay system that is equivalent to the infectious SARS-CoV-2 is a promising tool for high-throughput screening of large compound libraries for viral entry inhibitors against SARS-CoV-2 along with toxicity and effects on syncytia. Studies using clinical isolates of SARS-CoV-2 are warranted to confirm the antiviral potency of the leads and the utility of the screening system.

This study aims to illustrate the complex relationships between reading motivation and reading comprehension for Black girl readers. There is an urgent need for research that explicitly centers on the reading motivations of Black girls through a humanizing, asset-oriented lens. Through a Situative Black Girlhood Reading Motivations lens, which integrates a situative perspective on motivation and the tenets of Black Girlhood Studies, this multi-year study focuses on a group of Black girl readers participating in a summer reading program. Qualitative data, including video observations, student work artifacts, and small-group artifact-elicited interviews, were analyzed through a generic inductive approach to answer the research question, “How are relationships between Black girls’ reading motivations and their reading comprehension evident in their reading engagement and enactments?” The findings demonstrate that the participants’ most salient reading motivations in this instructional context (meaning-oriented, collaborative, and liberatory reading motivations) (1) were a precursor to their comprehension, (2) worked in tandem with their comprehension, and (3) stemmed from their comprehension. These findings contribute to models of reading by illustrating the need for additional complexity when describing the relationship between reading motivation and comprehension.

Background: Cataracts resulting from equine recurrent uveitis (ERU) or other forms of uveitis are usually associated with rapid progression. ERU is the most common ocular disease cause of blindness and cause of cataracts in horses. The necessity for the posterior capsulorhexis (PC) during phacoemulsification (PE) is controversial. This study aimed to evaluate vision and complications after PE combined with pars plana vitrectomy (PPV) in horses with uveitis-associated cataracts and compare the PE technique with and without posterior capsulorhexis. Methods: Thirty-two eyes of 28 horses with uveitis-associated cataracts aged 14 months to 19.6 years were treated with PE-PPV under identical conditions. Twenty-three eyes of 21 horses were affected by an ERU-associated (ERU group), and nine eyes of 7 horses were affected by cataracts related to uveitis with pathogenesis different to ERU (non-ERU group). PE-PPV was performed in 12 eyes of 10 horses (PC group) and 20 eyes of 18 horses without posterior capsulorhexis (NPC group). Follow-up examination was performed at a mean of 1.7 ± 1.8 years postoperatively (range: 1 month–6.4 years). Results: In the period up to 1 month postoperatively, 17/20 (85%) NPC-eyes and 8/12 (67%) PC-eyes (total: 25/32 [78%]) were visual. From 1–6 months postoperatively, 16/20 (80%) NPC-eyes and 7/12 (58.3%) PC-eyes (total: 23/32 [72%]), and from 6–12 months, 7/11 (63.6%) NPC-eyes and 3/8 (37.5%) PC-eyes (total: 10/19 [52.6%]) were visual. From 12–18 months postoperatively, 3/7 (42.9%) NPC-eyes and 2/9 (22.2%) PC-eyes (total: 5/16 [31.3%]), and from 18–24 months, 3/8 (37.5%) NPC-eyes and 1/8 (12.5%) PC-eyes (total: 4/16 [25%]) were visual. After 24 months postoperatively, 2/7 (28.6%) NPC-eyes and 1/8 (12.5%) PC-eyes (total: 3/15 [20%]) were visual. Despite the higher number of visual eyes in the NPC group at each time point, differences were not significant. No obvious differences regarding postsurgical vision were observed between the ERU- and non-ERU groups at each time point. In the overall population, a significant decrease in the number of eyes with postoperative active uveitis was observed during the follow-up examinations (p < 0.001). A significant increase in the number of eyes that were blind due to retinal detachment was observed in the overall patient population as the examination period progressed (p < 0.001). Retinal detachment was the sole long-term cause of blindness. Conclusions: In horses diagnosed with uveitis-associated cataracts and treated with PE-PPV, no persistent active uveitis was observed in the present study during follow-up examinations. However, the proportion of eyes that were blind due to retinal detachment increased. Whilst PE-PPV may prevent postsurgical persistent active uveitis and remove lens opacity, the prognosis for a visual outcome is guarded. A superior outcome in postsurgical vision was observed in the NPC group. However, caution is required when interpreting these results due to several factors that affect the independent comparison of the surgical groups.

COVID-19 vaccines have been shown to be effective in preventing severe illness, including among pregnant persons. The vaccines appear to be safe in pregnancy, supporting a continuously favorable overall risk/benefit profile, though supportive data for the U.S. over different periods of variant predominance are lacking. We sought to analyze the association of adverse pregnancy outcomes with COVID-19 vaccinations in the pre-Delta, Delta, and Omicron SARS-CoV-2 variants’ dominant periods (constituting 50% or more of each pregnancy) for pregnant persons in a large, nationally sampled electronic health record repository in the U.S. Our overall analysis included 311,057 pregnant persons from December 2020 to October 2023 at a time when there were approximately 3.6 million births per year. We compared rates of preterm births and stillbirths among pregnant persons who were vaccinated before or during pregnancy to persons vaccinated after pregnancy or those who were not vaccinated. We performed a multivariable Poisson regression with generalized estimated equations to address data site heterogeneity for preterm births and unadjusted exact models for stillbirths, stratified by the dominant variant period. We found lower rates of preterm birth in the majority of modeled periods (adjusted incidence rate ratio [aIRR] range: 0.42 to 0.85; p-value range: p-value range:

Abstract Autism has been characterized by a tendency to attend to the local visual details over surveying an image to understand the gist–a phenomenon called local interference. This sensory processing trait has been found to negatively impact social communication. Although much work has been conducted to understand these traits, little to no work has been conducted to intervene to provide support for local interference. Additionally, recent understanding of autism now introduces the core role of sensory processing and its impact on social communication. However, no interventions to the end of our knowledge have been explored to leverage this relationship. This work builds on the connection between visual attention and semantic representation in autistic children. In this work, we ask the following research questions: RQ1: Does manipulating image characteristics of luminance and spatial frequency increase likelihood of fixations in hot spots (Areas of Interest) for autistic children? RQ2: Does manipulating low-level image characteristics of luminance and spatial frequency increase the likelihood of global verbal responses for autistic children? We sought to manipulate visual attention as measured by eye gaze fixations and semantic representation of verbal response to the question “What is this picture about?”. We explore digital strategies to offload low-level, sensory processing of global features via digital filtering. In this work, we designed a global filter to reduce image characteristics found to be distracting for autistic people and compared baseline images to featured images in 11 autistic children. Participants saw counterbalanced images way over 2 sessions. Eye gaze in areas of interest and verbal responses were collected and analyzed. We found that luminance in non-salient areas impacted both eye gaze and verbal responding–however in opposite ways (however versus high levels of luminance). Additionally, the interaction of luminance and spatial frequency in areas of interest is also significant. This is the first empirical study in designing an assistive technology aimed to augment global processing that occurs at a sensory-processing and social-communication level. Contributions of this work include empirical findings regarding the quantification of local interference in images of natural scenes for autistic children in real-world settings; digital methods to offload global visual processing to make this information more accessible via insight on the role of luminance and spatial frequency in visual perception of and semantic representation in images of natural scenes.

Background: Healthcare providers at primary care Federally Qualified Healthcare Centers (FQHC) and an Accountable Care Organizations (ACO) collaborated with clinical pharmacists in providing patient care utilizing the comprehensive medication management (CMM) framework. The intention of CMM was to generate more time for providers to see patients, and to improve overall patient quality of life. Objectives: The purpose of this study was to survey the providers' views of clinical pharmacy services, and to compare and contrast the shared-visit model in rural FQHCs and an ACO collaborative practice agreement model in a mid-sized metropolitan area. Methods: Primary care providers completed a five-domain 22-item survey of provider patient care, provider pharmacy consults, provider ranking of pharmacy-services, disease treatment and provider views on the value of clinical pharmacists. Results: FQHC pharmacists were available one day per week (75%), while 69% of ACO pharmacists were available five days per week. FQHC providers requested 10 consults per week (44%). Both organizations had nearly identical provider rankings and impact on patient care for clinical pharmacy services and disease-focused pharmacy services. The provider survey of satisfaction with pharmacy consultations were highly positive and scored as strongly agree with FQHC and ACO, with the exception of three items with the FQHC. Overall providers at both organizations report highly effective medication-related improvements, disease outcomes and also recommend clinical pharmacists to other providers and primary care teams. Regression analysis revealed relevant clinical associations between survey statements not seen with individual survey items alone. Conclusion: Primary care providers report high satisfaction with, and benefits of, clinical pharmacy services. Drug information resource and disease-focused management were documented by providers as valuable pharmacy services. Providers promoted expanding the role of clinical pharmacists with providers, and integration into primary care teams.

BackgroundIn Australia, the distribution of occupational therapists, physiotherapists, and podiatrists density (per 10,000 population) by measure of location/rurality, usual resident population, and area-level socioeconomic status has not been described.ObjectiveTo describe the national as well as states-and territories-wide distribution of registered allied health workforce-occupational therapists, physiotherapists, and podiatrists-by measures of rurality and area-level socioeconomic position in Australia.MethodsA linked data study that brings together (1) the location of health practitioners' principal place of practice from the Australian Health Practitioner Regulation Agency, (2) a measure of location/rurality-Modified Monash Model (MMM), and (3) an area-level measure of socioeconomic status-Index of Relative Socio-Economic Advantage and Disadvantage (IRSAD). The provider-to-population ratio (i.e., density) of three Australia's allied health workforce (occupational therapists, physiotherapists, and podiatrists) was calculated according to the MMM classifications (i.e., Modified Monash 1-7) and IRSAD quintiles at state and national level.ResultsNationwide, the density of occupational therapists and physiotherapists was highest in metropolitan areas (Modified Monash 1) and decreased with the increasing levels of the MMM categories. The national density of podiatrists was highest in Modified Monash 3 areas. The density of occupational therapists, physiotherapists, and podiatrists was highest in areas with IRSAD quintile 5 (i.e., the highest socioeconomic position) and decreased with the declining levels of the IRSAD quintiles nationwide. Moreover, there were notable disparities in the density of occupational therapists, physiotherapists, and podiatrists across each state and territory in Australia when stratified by the MMM classifications and IRSAD quintiles.ConclusionsThere was uneven distribution of registered occupational therapists, physiotherapists, and podiatrists when stratified by measures of location/rurality and area-level socioeconomic status across Australian jurisdictions. The density of these three groups of allied health workforce tended to be more concentrated in metropolitan and most advantaged areas while remote and most disadvantaged areas exhibited less allied health workforce distribution across each state and territory.

Background: With cancer as one of the leading causes of death worldwide, accurate primary tumor type prediction is critical in identifying genetic factors that can inhibit or slow tumor progression. There have been efforts to categorize primary tumor types with gene expression data using machine learning, and more recently with deep learning, in the last several years. Methods In this paper, we developed four 1-dimensional (1D) Convolutional Neural Network (CNN) models to classify RNA-seq count data as one of 17 highly represented primary tumor types or 32 primary tumor types regardless of imbalanced representation. Additionally, we adapted the models to take as input either all Ensembl genes (60,483) or protein coding genes only (19,758). Unlike previous work, we avoided selection bias by not filtering genes based on expression values. RNA-seq count data expressed as FPKM-UQ of 9,025 and 10,940 samples from The Cancer Genome Atlas (TCGA) were downloaded from the Genomic Data Commons (GDC) corresponding to 17 and 32 primary tumor types respectively for training and validating the models. Results: All 4 1D-CNN models had an overall accuracy of 94.7% to 97.6% on the test dataset. Further evaluation indicates that the models with protein coding genes only as features performed with better accuracy compared to the models with all Ensembl genes for both 17 and 32 primary tumor types. For all models, the accuracy by primary tumor type was above 80% for most primary tumor types. Conclusions: We packaged all 4 models as a Python-based deep learning classification tool called TULIP ( TU mor C L ass I fication P redictor) for performing quality control on primary tumor samples and characterizing cancer samples of unknown tumor type. Further optimization of the models is needed to improve the accuracy of certain primary tumor types.

Objectives To explore and synthesise the evidence relating to features of quality in rural health student placements.Design Scoping review.Data sources MEDLINE, CINAHL, Embase, ProQuest, Informit, Scopus, ERIC and several grey literature data sources (1 January 2005 to 13 October 2020).Study selection The review included peer-reviewed and grey literature from Organisation for Economic Co-operation and Development listed countries that focused on quality of health student placements in regional, rural and remote areas.Data extraction Data were extracted regarding the methodological and design characteristics of each data source, and the features suggested to contribute to student placement quality under five categories based on a work-integrated learning framework.Results Of 2866 resulting papers, 101 were included for data charting and content analysis. The literature was dominated by medicine and nursing student placement research. No literature explicitly defined quality in rural health student placements, although proxy indicators for quality such as satisfaction, positive experiences, overall effectiveness and perceived value were identified. Content analysis resulted in four overarching domains pertaining to features of rural health student placement quality: (1) learning and teaching in a rural context, (2) rural student placement characteristics, (3) key relationships and (4) required infrastructure.Conclusion The findings suggest that quality in rural health student placements hinges on contextually specific features. Further research is required to explore these findings and ways in which these features can be measured during rural health student placements.

This study focuses on student resilience during the COVID-19 crisis, a key factor for students' progress, and future careers. It does so by introducing the job demands and resources (JDR) model, and the social exchange theory (SET), widely adopted in the management literature in the education field to better understand student experience management in the higher education context. In past research, limited attention has been given to student resilience through the lens of management theories such as JDR and SET, and college support as a factor that develops student resilience has been scarcely observed. Data were collected from 1435 students in a large Irish university during the lockdown period due to COVID-19 in 2020. The findings reveal that college support, as a resource, develops students' resilience (even in the presence of higher study demands), which in turn decreases their affective response to crisis, and increases their adaptive study performance, and commitment to the move to online learning. This research suggests that colleges need to balance their support and demands towards students during the crisis in facilitating students to develop their own resilience and provides valuable insights for higher education sector to develop students' resilience during crisis.

Luminal breast cancer subtypes respond poorly to endocrine and trastuzumab treatments due to cellular heterogeneity arising from the phenotype transitions, accounted for mainly by the loss of receptor expression. The origins of basal-like and human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer subtypes have been attributed to genetic and protein modifications in stem-like cells and luminal progenitor cell populations, respectively. The post-transcriptional regulation of protein expression is known to be influenced by microRNAs (miRNAs) that are deemed to be master regulators of several biological processes in breast tumorigenesis and progression. Our objective was to identify the fractions of luminal breast cancer cells that share stemness potentials and marker profiles and to elucidate the molecular regulatory mechanism that drives transitions between fractions, leading to receptor discordances. Established breast cancer cell lines of all prominent subtypes were screened for the expression of putative cancer stem cell (CSC) markers and drug transporter proteins using a side population (SP) assay. Flow-cytometry-sorted fractions of luminal cancer cells implanted in immunocompromised mice generated a pre-clinical estrogen receptor alpha (ERα+) animal model with multiple tumorigenic fractions displaying differential expression of drug transporters and hormone receptors. Despite an abundance of estrogen receptor 1 (ESR1) gene transcripts, few fractions transitioned to the triple-negative breast cancer (TNBC) phenotype with a visible loss of ER protein expression and a distinct microRNA expression profile that is reportedly enriched in breast CSCs. The translation of this study has the potential to provide novel therapeutic miRNA-based targets to counter the dreaded subtype transitions and the failure of antihormonal therapies in the luminal breast cancer subtype.

Abstract Background Pressure offloading treatment is critical for healing diabetes‐related foot ulcers (DFU). Yet the 2011 Australian DFU guidelines regarding offloading treatment are outdated. A national expert panel aimed to develop a new Australian guideline on offloading treatment for people with DFU by adapting international guidelines that have been assessed as suitable to adapt to the Australian context. Methods National Health and Medical Research Council procedures were used to adapt suitable International Working Group on the Diabetic Foot (IWGDF) guidelines to the Australian context. We systematically screened, assessed and judged all IWGDF offloading recommendations using best practice ADAPTE and GRADE frameworks to decide which recommendations should be adopted, adapted or excluded in the Australian context. For each recommendation, we re‐evaluated the wording, quality of evidence, strength of recommendation, and provided rationale, justifications and implementation considerations, including for geographically remote and Aboriginal and Torres Strait Islander peoples. This guideline, along with five accompanying Australian DFU guidelines, underwent public consultation, further revision and approval by ten national peak bodies (professional organisations). Results Of the 13 original IWGDF offloading treatment recommendations, we adopted four and adapted nine. The main reasons for adapting the IWGDF recommendations included differences in quality of evidence ratings and clarification of the intervention(s) and control treatment(s) in the recommendations for the Australian context. For Australians with plantar DFU, we recommend a step‐down offloading treatment approach based on their contraindications and tolerance. We strongly recommend non‐removable knee‐high offloading devices as first‐line treatment, removable knee‐high offloading devices as second‐line, removable ankle‐high offloading devices third‐line, and medical grade footwear as last‐line. We recommend considering using felted foam in combination with the chosen offloading device or footwear to further reduce plantar pressure. If offloading device options fail to heal a person with plantar DFU, we recommend considering various surgical offloading procedures. For people with non‐plantar DFU, depending on the type and location of the DFU, we recommend using a removable offloading device, felted foam, toe spacers or orthoses, or medical grade footwear. The six new guidelines and the full protocol can be found at: https://diabetesfeetaustralia.org/new‐guidelines/. Conclusions We have developed a new Australian evidence‐based guideline on offloading treatment for people with DFU that has been endorsed by ten key national peak bodies. Health professionals implementing these offloading recommendations in Australia should produce better DFU healing outcomes for their patients, communities, and country.

The contribution of satellite glia to peripheral nerve regeneration is unclear. Here, the authors show that satellite glia are transcriptionally distinct from Schwann cells, share similarities with astrocytes, and, upon injury, they contribute to axon regeneration via Fasn-PPARα signalling pathway.

This article addresses tensions between how researchers have conceptualized and operationalized adolescent reading motivation and how a group of Black girl readers perceive and enact reading motivation. Through a grounded theory approach, this qualitative study offers an initial exploration into mapping a race-reimaged reading motivation construct by centering the views, through artifact-elicited interviews, and experiences, through classroom observations, of a group of adolescent Black girl readers. Findings point to a need to reconceptualize reading motivation so that researchers and practitioners are equipped to recognize Black girls' reading motivations.

The Cas12b family of CRISPR nucleases has been underutilized in mammalian cells due to the high temperature requirement of known members. Here the authors engineer BhCas12b to overcome this limitation for robust and specific genome editing applications in human cells.

Ultrasound can be used to assess injury and structural changes to the soft-tissue structure of the foot. It may be useful to assess the feet of people with diabetes who are at increased risk of plantar soft-tissue pathological changes. The aim of this study was to determine if ultrasound measurements of plantar soft-tissue thickness and assessments of tissue acoustic characteristics are reliable in people with and without diabetes mellitus. A repeated measures design was used to determine intra-observer reliability for ultrasound measurements of plantar skin and fat pad thickness and intra- and inter-observer reliability of plantar skin and fat pad tissue characterisation assessments made at foot sites which are at risk of tissue injury in people with diabetes. Thickness measurements and tissue characterisation assessments were obtained at the heel and forefoot in both the unloaded and compressed states and included discrete layers of the plantar tissues: skin, microchamber, horizontal fibrous band, macrochamber and total soft-tissue depth. At each site, relative intra-observer reliability was achieved for the measurement of at least one plantar tissue layer. The total soft-tissue thickness measured in the unloaded state (ICC 0.925-0.976) demonstrated intra-observer reliability and is the most sensitive for detecting small change on repeated measures. Intra-observer agreement was demonstrated for tissue characteristic assessments of the skin at the heel (k = 0.70), fat pad at the lateral sesamoid region (k = 0.70) and both skin and fat pad at the second (k = 0.80, k = 0.70 respectively) and third metatarsal heads (k = 0.90, k = 0.79 respectively). However, acceptable inter-observer agreement was not demonstrated for any tissue characteristic assessment, therefore the use of multiple observers should be avoided when making these assessments.

Objective: To understand the patient-influenced activities and characteristics associated with return to a single postacute care transitional care clinic visit in a cohort of patients cared for at the test health system site of the larger Comprehensive Post-Acute Stroke Services (COMPASS) cluster randomized trial. Design: Retrospective cohort. Setting: A large health system. Participants: Patients discharged directly home between June 2016 and June 2018 after sustaining a stroke who did not receive formal inpatient rehabilitation services while being cared for in a single comprehensive stroke center, defined as a center that meet standards to rapidly diagnose and treat the most complex stroke cases. Interventions: Study participants had the opportunity to participate in a (1) 2-day call, (2) comprehensive care transitions clinic visit, and (3) individualized care plan. Main Outcome Measures: Patient participation in a single postacute care comprehensive care transitions visit, ideally completed within 7-14 calendar days post discharge vs not attending this visit. Care transition visits are where the responsibility for preventive care, other services, and posthospital follow-up are transitioned to outpatient providers. Results: Among 1300 eligible patients (mean age 64.8 years; 45% female; 25.4% nonwhite; 9.7% uninsured), 95.7% had follow-up clinic visits scheduled before discharge, 22.6% received home health referrals before discharge, 60.2% completed the 2-day call, and 63.2% attended the COMPASS visit. Among attendees, 33.2% attended by day 14, 71.3% attended within 30 days, and 28.7% attended after day 30. The median driving distance to the COMPASS visit was 45.9 miles or 73.9 km. Odds of visit attendance were higher if COMPASS 2-day follow up calls were completed, if follow-up clinic appointments were scheduled before discharge, if the patient had a primary care provider, and if the patients experienced a stroke vs a transient ischemic attack. Additionally, when we used the number of referrals at hospital discharge for different types of outpatient therapy as a surrogate marker of poststroke impairment, patients having no therapy referrals (milder to no impairments) had lower odds of attending the COMPASS visit than those with 1 therapy referral. Likewise, those with more than 1 referral were also less likely to attend the COMPASS visit. Conclusions: This analysis highlights that scheduling visits at discharge and completing timely telephone follow-up shortly after discharge may lead to greater adherence to in-person clinic follow-up after stroke. Keywords: Outcome assessment, health care, Patient transfer, Rehabilitation, Subacute care

Fast scan cyclic voltammetry (FSCV) is an electrochemical technique that allows sub-second detection of oxidizable chemical species, including monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin. This technique has been used to record the physiological dynamics of these neurotransmitters in brain tissue, including their rates of release and reuptake as well as the activity of neuromodulators that regulate such processes. This protocol will focus on the use of ex vivo FSCV for the detection of dopamine within the nucleus accumbens in slices obtained from rodents. We have included all necessary materials, reagents, recipes, procedures, and analyses in order to successfully perform this technique in the laboratory setting. Additionally, we have also included cautionary points that we believe will be helpful for those who are novices in the field.

INTRODUCTION:Diabetes mellitus (DM) is associated with hyperglycaemia and advanced glycosylation end-products. In the foot, the consequences of chronic or uncontrolled diabetes are micro and macrovascular disease, neuropathy, reduced joint mobility and structural and soft tissue changes that increase the risk of ulcer development and amputation. Diabetes foot assessment currently includes a comprehensive history, neurological and vascular assessments and examination focussed on dermatological and musculoskeletal abnormalities. Whilst these assessments are helpful for predicting ulceration risk, direct identifiers that enable early therapeutic intervention are lacking. The intention of this review was to ascertain if B-mode ultrasound could be clinically applied to identify structural change in the diabetic foot and be utilised as an early predictor of ulceration risk. METHODS:Primary databases and grey literature sources were systematically searched. Selection criteria were that the study included a diabetic sample and used B-mode ultrasound to assess soft tissue structures of the foot (plantar skin, plantar fat pad or intrinsic muscles). RESULTS:Fifteen studies were identified for inclusion (combined diabetic sample of 773). Ultrasound demonstrated reductions in tissue thickness in diabetics compared to non-diabetics under first (p = 0.01) and second (p = 0.03) metatarsal heads, but not the third (p = 0.24). Statistical heterogeneity was high for ultrasound thickness measures under metatarsal heads four/five (I2 65%, 81%) and very high for plantar skin (I2 98%), heel pad (I2 76%) and intrinsic muscles (I2 91%, 81%). Extensor digitorum brevis (EDB) ultrasound measures were significantly thinner in diabetics for all dimension measures compared to healthy controls except one study, which reported no significant differences in EDB thickness. CONCLUSIONS:No direct evidence was found to indicate B-mode ultrasound measures can predict soft tissue changes in the plantar foot in diabetes, although low level studies indicate ultrasound has the potential to identify structural change. Clinical, methodological and statistical heterogeneity limit result applicability. This review highlights the need for robust prospective longitudinal research to examine the predictive validity of this method.

Understanding natural immunologic control over Human Immunodeficiency Virus (HIV)-1 replication, as occurs in rare long-term nonprogressors/elite controllers (LTNP/EC), should inform the design of efficacious HIV vaccines and immunotherapies. Durable control in LTNP/EC is likely mediated by highly functional virus-specific CD8+ T-cells. Protective Human Leukocyte Antigen (HLA) class I alleles, like B*27 and B*57, are present in most, but not all LTNP/EC, providing an opportunity to investigate features shared by their HIV-specific immune responses. To better understand the contribution of epitope targeting and conservation to immune control, we compared the CD8+ T-cell specificity and function of B*27/57neg LTNP/EC (n = 23), B*27/57pos LTNP/EC (n = 23) and B*27/57neg progressors (n = 13). Fine mapping revealed 11 previously unreported immunodominant responses. Although B*27/57neg LTNP/EC did not target more highly conserved epitopes, their CD8+ T-cell cytotoxic capacity was significantly higher than progressors. Similar to B*27/57pos LTNP/EC, this superior cytotoxicity was mediated by preferential expansion of immunodominant responses and lysis through the predicted HLA. These findings suggest that increased CD8+ T-cell cytotoxic capacity is a common mechanism of control in most LTNP/EC regardless of HLA type. They also suggest that potent cytotoxicity can be mediated through various epitopes and HLA molecules and could, in theory, be induced in most people.