Assessment of SOX10 expression in 437 canine neoplasms of different embryologic origins.

Several members of the SRY-related HMG-box (SOX) protein family are implicated in tumorigenesis, metastasis, and regulation of the tumor microenvironment. SOX10, which is involved in neural crest cell migration and differentiation, has long been recognized a sensitive and specific immunohistochemical (IHC) marker in the diagnosis of melanoma in humans. However, expression of SOX10 in other tumor types has infrequently been evaluated in humans until recently and has not been thoroughly investigated in the dog. Our aim was to characterize the expression of SOX10 in canine neoplasms to objectively assess its value as a diagnostic IHC marker. Immunohistochemistry for SOX10 was performed on 437 archived, formalin-fixed paraffin-embedded tissues from representative canine neoplasms of ectodermal (15 tumor types), mesodermal (13 tumor types), endodermal (8 tumor types), and mixed/unknown (7 tumor types) embryologic origin. Oral and cutaneous tumors of melanocytic origin were used as positive controls. Intense SOX10 immunolabeling was observed in most tumors of ectodermal origin, including consistent expression in mammary carcinomas, and gliomas. Embryonal and hair follicle neoplasms inconsistently exhibited strong nuclear immunolabeling. Oral fibrosarcomas and undifferentiated oral sarcomas both inconsistently exhibited moderate to strong nuclear immunolabeling. Neoplasms of mesodermal and endodermal origin lacked immunolabeling. Salivary carcinomas, representing an unknown/mixed embryologic origin, were strongly labeled. SOX10 expression is not limited to melanomas, but is expressed by canine tumors of diverse tissues and embryologic derivation. Importantly, expression of SOX10 by a subset of oral sarcomas impairs its value as a marker for spindle cell oral melanomas.

Social determinants of health disparities impact postoperative complications in patients undergoing total shoulder arthroplasty.

BACKGROUND: Understanding the role of social determinants of health disparities (SDHDs) in surgical outcomes can better prepare providers to improve postoperative care. In this study, we use International Classification of Diseases (ICD) codes to identify SDHDs and investigate the risk of postoperative complication rates among patients undergoing total shoulder arthroplasty (TSA). METHODS: A retrospective cohort analysis was conducted using a national insurance claims database. Using ICD and Current Procedural Terminology (CPT) codes, patients who underwent primary TSA with at least 2 years of follow-up in the database were identified. Patients with a history of SDHDs were identified using appropriate ICD-9 and ICD-10 codes. Patients were grouped in one of 2 cohorts: (1) patients with no history of SDHDs (control) and (2) patients with a history of SDHDs (SDHD group) prior to TSA. The SDHD and control groups were matched 1:1 for comorbidities and demographics prior to conducting multivariable analysis for 90-day medical complications and 2-year surgical complications. RESULTS: After matching, there were 8023 patients in the SDHD group and 8023 patients in the control group. The SDHD group had significantly higher odds for 90-day medical complications including heart failure, cerebrovascular accident, renal failure, deep vein thrombosis, pneumonia, sepsis, and urinary tract infection. Additionally, the SDHD group had significantly higher odds for revision surgery within 2 years following TSA. Patients in the SDHD group also had a significantly longer length of hospital stay following TSA. DISCUSSION: This study highlights the association between SDHDs and postoperative complications following TSA. Quantifying the risk of complications and differences in length of stay for TSA patients with a history of SDHDs is important in determining value-based payment models and risk stratifying to optimize patient care.

Novel 3D Force Sensors for a Cost-Effective 3D Force Plate for Biomechanical Analysis.

Three-dimensional force plates are important tools for biomechanics discovery and sports performance practice. However, currently, available 3D force plates lack portability and are often cost-prohibitive. To address this, a recently discovered 3D force sensor technology was used in the fabrication of a prototype force plate. Thirteen participants performed bodyweight and weighted lunges and squats on the prototype force plate and a standard 3D force plate positioned in series to compare forces measured by both force plates and validate the technology. For the lunges, there was excellent agreement between the experimental force plate and the standard force plate in the X-, Y-, and Z-axes (r = 0.950-0.999, p < 0.001). For the squats, there was excellent agreement between the force plates in the Z-axis (r = 0.996, p < 0.001). Across axes and movements, root mean square error (RMSE) ranged from 1.17% to 5.36% between force plates. Although the current prototype force plate is limited in sampling rate, the low RMSEs and extremely high agreement in peak forces provide confidence the novel force sensors have utility in constructing cost-effective and versatile use-case 3D force plates.

Risk factors, time to onset and recurrence of delirium in a mixed medical-surgical ICU population: A secondary analysis using Cox and CHAID decision tree modeling.

A retrospective secondary analysis of 4,200 patients was collected from two academic medical centers. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in all patients. Univariate and multivariate Cox models, logistic regression analysis, and Chi-square Automatic Interaction Detector (CHAID) decision tree modeling were used to explore delirium risk factors. Increased delirium risk was associated with exposed only to artificial light (AL) hazard ratio (HR) 1.84 (95 % CI: 1.66-2.044, P<0.001), physical restraint application 1.11 (95 % CI: 1.001-1.226, P=0.049), and high nursing care requirements (>8 hours per 8-hour shift) 1.18 (95 % CI: 1.048-1.338, P=0.007). Delirium incidence was inversely associated with greater family engagement 0.092 (95 % CI: 0.014-0.596, P=0.012), low staff burnout and anticipated turnover scores 0.093 (95 % CI: 0.014-0.600, P=0.013), non-ICU length-of-stay (LOS)<15 days 0.725 (95 % CI: 0.655-0.804, P<0.001), and ICU LOS ≤15 days 0.509 (95 % CI: 0.456-0.567, P<0.001). CHAID modeling indicated that AL exposure and age <65 years were associated with a high risk of delirium incidence, whereas SOFA score ≤11, APACHE IV score >15 and natural light (NL) exposure were associated with moderate risk, and female sex was associated with low risk. More rapid time to delirium onset correlated with baseline sleep disturbance (P=0.049), high nursing care requirements (P=0.019), and prolonged ICU and non-ICU hospital LOS (P<0.001). Delirium recurrence correlated with age >65 years (HR 2.198; 95 % CI: 1.101-4.388, P=0.026) and high nursing care requirements (HR 1.978, 95 % CI: 1.096-3.569), with CHAID modeling identifying AL exposure (P<0.001) and age >65 years (P=0.032) as predictive variables. Development of ICU delirium correlated with application of physical restraints, high nursing care requirements, prolonged ICU and non-ICU LOS, exposure exclusively to AL (rather than natural), less family engagement, and greater staff burnout and anticipated turnover scores. ICU delirium occurred more rapidly in patients with baseline sleep disturbance, and recurrence correlated with the presence of delirium on ICU admission, exclusive AL exposure, and high nursing care requirements.

Do disadvantaged schools have poorer teachers? Rethinking assumptions about the relationship between teaching quality and school-level advantage.

Improving educational performance, including narrowing equity gaps, is frequently touted as a matter of improving the quality of teachers in the lowest performing, often disadvantaged, schools. However, the assumption that teaching is of poorer quality in disadvantaged schools is largely unsubstantiated. Using the Quality Teaching Model of pedagogy, we observed 832 lessons in 193 New South Wales primary schools and found a small relationship between teaching quality and school-level advantage. However, when 174 teachers from across the school spectrum participated in Quality Teaching Rounds we found equivalent, and substantial, gains in teaching quality across all levels of school advantage. This result indicates that differences in teaching quality are less a reflection of teacher capabilities than of the challenging circumstances in disadvantaged schools. We argue that policies seeking more equitable achievement should address wider social inequities, rather than unfairly blaming teachers for being unable to level an unequal playing field.

Hemoperitoneum identified by focused assessment with sonography for trauma following cardiopulmonary resuscitation.

It is generally recognized that lives are saved by administering high-quality cardiopulmonary resuscitation (CPR) to patients in cardiac arrest. A focused assessment with sonography for trauma (FAST) examination is an effective and non-invasive method for detecting rare complications of CPR, such as hemorrhage from abdominal visceral injury. We report the case of a 56-year-old female suffering from intra-abdominal hemorrhage caused by a liver laceration following CPR. The hemoperitoneum was diagnosed by a FAST examination. Although severe complications of CPR are rare, they can be easily detected with the use of a FAST examination. A FAST examination should be considered as a post-resuscitation approach to assess for life-threatening complications in all patients following cardiopulmonary resuscitation.

Rationale and study protocol for the Movement Oriented Games Based Assessment (MOGBA) cluster randomized controlled trial: A complex movement skill intervention for 8-12 year old children within 'Made to Play'.

There is a positive relationship between children's movement competence and physical activity, with a further relationship established between physical activity and childhood obesity. The Movement Oriented Games Based Assessment (MOGBA) is a delivery and assessment intervention designed to improve children's complex movement skills, based on principles of motor development and assessment theories. MOGBA aims to improve children's movement competence, physical fitness and self-perceptions (physical and game) and increase children's moderate-to-vigorous physical activity (MVPA). MOGBA is to be used in the 'Made to Play' initiative, involving 105 sports and activity programs across 21 countries, involving over 25 million children. A multi-site cluster randomized controlled trial will take place across three global sites (UK, Ireland and Australia). Each site will recruit eight primary schools (four experiment, four control) with each school providing two separate classes of children from age ranges 8-12 years (Site n = ~300, total n = 904). After baseline assessments, schools will be randomly allocated to an experimental or wait-list control group. Following two half-day workshops, trained facilitators will deliver the MOGBA intervention for 9 weeks. The main intervention components include delivery of 14 games-based activities with associated assessments of children's movement and differentiation to meet children's needs by manipulating space, effort and relationships. The primary outcome of the trial is to improve children's' movement competence (The Dragon Challenge), with secondary outcomes of improving children's' in-activity and leisure-time MVPA (5-day accelerometer), physical fitness (standing long jump and push ups) and self-perceptions (physical and game). Data will be analysed using multilevel modelling approaches. The MOGBA intervention has been designed to improve children's movement competence and scalable interventions based on MOGBA could be applied across programs within the Made to Play initiative, globally. The trial is registered at the Australia New Zealand Clinical Trial Registry (ACTRN12619001320145p, 27 Sep 2019).

Transitional care management visits to improve coordination of care.

OBJECTIVES: This report aimed to determine whether transitional care management (TCM) services, provided by Inspira Care Connect, LLC (ICC), a Track 1 Medicare Shared Savings Program accountable care organization, were effective in reducing 30-day readmission rates, observation stay days, and emergency department visits, along with mortality rates, total costs, and frequency of primary care physician (PCP) visits among Medicare beneficiaries served by ICC. STUDY DESIGN: In accordance with TCM programming, ICC contacted the majority of patients telephonically within 48 business hours after discharge from an inpatient setting and scheduled a face-to-face visit with the patient's PCP within 1 to 14 days after discharge from an inpatient setting. The patients were provided with non-face-to-face services as needed throughout the 30-day period. METHODS: The effectiveness of the TCM model was measured using a retrospective propensity score matching design, which allowed for an accurate comparison between those who received TCM and similar ICC Medicare beneficiaries who did not. The analysis utilized Medicare parts A and B claims from January 1, 2016, to December 31, 2017. RESULTS: Patients who received TCM had lower 30-day readmission rates than those who did not (P < .05). CONCLUSIONS: The services provided to ICC Medicare patients through the TCM model may have enhanced the ability to identify problems at an earlier stage, resulting in the prevention of complications and unnecessary utilization of costly health care services.

New opportunities for designing effective small interfering RNAs.

Small interfering RNAs (siRNAs) that silence genes of infectious diseases are potentially potent drugs. A continuing obstacle for siRNA-based drugs is how to improve their efficacy for adequate dosage. To overcome this obstacle, the interactions of antiviral siRNAs, tested in vivo, were computationally examined within the RNA-induced silencing complex (RISC). Thermodynamics data show that a persistent RISC cofactor is significantly more exothermic for effective antiviral siRNAs than their ineffective counterparts. Detailed inspection of viral RNA secondary structures reveals that effective antiviral siRNAs target hairpin or pseudoknot loops. These structures are critical for initial RISC interactions since they partially lack intramolecular complementary base pairing. Importing two temporary RISC cofactors from magnesium-rich hairpins and/or pseudoknots then kickstarts full RNA hybridization and hydrolysis. Current siRNA design guidelines are based on RNA primary sequence data. Herein, the thermodynamics of RISC cofactors and targeting magnesium-rich RNA secondary structures provide additional guidelines for improving siRNA design.

Integrating physical activity into the primary school curriculum: rationale and study protocol for the "Thinking while Moving in English" cluster randomized controlled trial.

BACKGROUND: The current and declining physical activity levels of children is a global concern. Integrating physical activity into the school curriculum may be an effective way not only to improve children's physical activity levels but also enhance educational outcomes. Given the recent national focus in Australia on improving the literacy levels of children in primary school, and an increasing proportion of time spent on explicitly teaching these skills, integrating physical activity into English could be a viable strategy to improve literacy levels and physical activity at the same time. The aim of this study is to evaluate the impact of the 'Thinking While Moving in English' (TWM-E) program on children's physical activity, on-task behavior in the classroom, academic achievement, and executive function. METHODS: Grade 3-4 children from 10 public schools in New South Wales, Australia will be randomly allocated to intervention (n = 5) or control (n = 5) groups. All teachers will receive 1-day workshop of registered professional learning and a TWM-E equipment pack (e.g., chalk, lettered bean bags). Intervention schools will be asked to adapt their English lessons to embed movement-based learning in their daily program for three 40-min lessons per week, over a six-week period. The primary outcome is children's physical activity levels across the school day (measured using accelerometry). Secondary outcomes are children's on-task behavior during English lessons, academic achievement in English, and executive function. A detailed process evaluation will be undertaken including questionnaires, fidelity checks, and teacher and student interviews. DISCUSSION: The TWM-E program has the potential to improve primary school children's physical activity levels, along with academic outcomes (on-task behavior, cognition, and academic achievement), and provide stakeholders with exemplar lessons and guidelines which illustrate how to teach English to children whilst they are moving. TRIAL REGISTRATION: Australian and New Zealand Clinical trial Register ACTRN12618001009202 Date registered: 15/06/2018 retrospectively registered.

Touch Surgery: Analysis and Assessment of Validity of a Hand Surgery Simulation "App".

BACKGROUND: Surgical educators are increasingly exploring surgical simulation and other nonclinical teaching adjuncts in the education of trainees. The simulators range from purpose-built machines to inexpensive smartphone or tablet-based applications (apps). This study evaluates a free surgery module from one such app, Touch Surgery, in an effort to evaluate its validity and usefulness in training for hand surgery procedures across varied levels of surgical experience. METHODS: Participants were divided into 3 cohorts: fellowship-trained hand surgeons, orthopedic surgery residents, and medical students. Participants were trained in the use of the Touch Surgery app. Each participant completed the Carpal Tunnel Release module 3 times, and participants' score was recorded for each trial. Participants also completed a customized Likert survey regarding their opinions on the usefulness and accuracy of the app. Statistical analysis using a 2-tailed t test and analysis of variance was performed to evaluate for performance within and between cohorts. RESULTS: All cohorts performed better on average with each subsequent simulation attempt. For all attempts, the experts outperformed the novice and intermediate participants, while the intermediate cohort outperformed the novice cohort. Novice users consistently gave the app better scores for usefulness as a training tool, and demonstrated more willingness to use the product. CONCLUSIONS: The study confirms app validity and usefulness by demonstrating that every cohort's simulator performance improved with consecutive use, and participants with higher levels of training performed better. Also, user confidence in this app's veracity and utility increased with lower levels of training experience.

Efficacy and feasibility of HIIT training for university students: The Uni-HIIT RCT.

OBJECTIVES: The primary aim of this study was to evaluate the preliminary efficacy and feasibility of an 8-week high-intensity interval training program (Uni-HIIT) for young adult students in a university setting. DESIGN: Randomised controlled trial. METHOD: Uni-HIIT was conducted at the University of Newcastle, Australia (February-June, 2017). Participants were university students 18-25yrs (n=53; 20.38±1.88yrs) randomized into the Uni HIIT program (n=26) or wait-list control (n=27) condition. Participants were required to attend up to three HIIT sessions/week for 8-weeks which included a variety of aerobic and muscular fitness exercise combinations lasting 8-12minutes (using 30:30sec rest:work intervals). The primary outcome was cardio-respiratory fitness (CRF) (20mSRT), and secondary outcomes included muscular fitness (standing jump, push-ups), body composition (InBody), executive function (Trail Making Test), anxiety levels (State Trait Anxiety Inventory) and perceived stress (Perceived Stress Scale). Linear mixed models were used to analyse outcomes and Cohen's d effect sizes were calculated. Process evaluation measures of recruitment, retention, attendance and satisfaction were conducted. RESULTS: A large significant group-by-time effect resulted for CRF [8.4 shuttles (95% CI(2.9-13.9), P=0.004,d=1.08] and muscular fitness [4.0 repetitions (95% CI(1.2-6.8), P=0.006,d=0.99], and moderate effect size was observed for Trail B [-5.9seconds (95% CI(-11.8-0.1.0), P=0.052, d=0.63]. No significant intervention effects were found for body composition, standing jump, anxiety or perceived stress (P >0.05). High ratings of participant satisfaction (4.73), enjoyment (4.54) and perceived value (4.54) were observed. CONCLUSION: This study demonstrates the efficacy and feasibility of delivering a novel HIIT program in the university setting.

Facilitating equitable prevention and management of gout for Maori in Northland, New Zealand, through a collaborative primary care approach.

INTRODUCTION The Gout Stop Programme was developed for primary care in Northland, New Zealand, to address inequitable health outcomes for Maori and Pacific people with gout. AIM The aim of the programme was to make it easier for clinicians to prescribe urate-lowering treatment, facilitate patient adherence through education and support, and reduce barriers to gout prevention and long-term management. METHODS From 2015 to 2017, patients with acute gout who met inclusion criteria were prescribed treatment according to a 'Gout Stop Pack' option, based on renal function and diabetes status. Patients were monitored by community pharmacists. Gout educators and a Gout Kaiawhina (community support worker) provided education and support to patients and whanau (families). Patient completion of the programme and outcomes, according to target serum urate level, were recorded. Patient experience was documented using a questionnaire and rating scale. RESULTS In total, 160 clinicians prescribed therapy at 887 patient presentations; 71% were Maori and Pacific patients. The completion rate was 55% in this group and 84% for the non-Maori and non-Pacific group. In the Maori and Pacific group, 40% reached the target serum urate level (≤0.36 mmol L-1) in 91 days, and 26% required further titration. In the non-Maori/non-Pacific group, these rates were 51% and 19% respectively. Following programme completion, 68% of Maori and Pacific patients and 65% of non-Maori and non-Pacific patients continued to take allopurinol. The 21 patients interviewed rated the programme as excellent or very good. DISCUSSION Culturally appropriate education and support for patients and the primary care team was essential. Collaboration between prescribers, community pharmacists and support workers reduced barriers to initiating prevention and long-term urate-lowering treatment and urate testing in this high-needs gout population.

Linking Sexual and Reproductive Health and Rights and HIV Services for Young People: The Link Up Project.

Sexual health and access to services are a pressing need for young people. This article introduces Link Up, a 3-year project in three African and two Asian countries, to enable and scale up access to integrated HIV services and sexual and reproductive health and rights for marginalized young people. The young people we worked with in this project included young men who have sex with men, young sex workers, young people who use drugs, young transgender people, young homeless people, and other vulnerable young people. The research and programmatic activities of Link Up, as illustrated in this Supplement, have highlighted the importance of recognizing and engaging with diversity among young people to improve access to services and outcomes protecting their health and human rights.

Impact of the Affordable Care Act Medicaid expansion on emergency department high utilizers with ambulatory care sensitive conditions: A cross-sectional study.

OBJECTIVES: The effect of the Affordable Care Act on emergency department (ED) high utilizers has not yet been thoroughly studied. We sought to determine the impact of changes in insurance eligibility following the 2014 Medicaid expansion on ED utilization for ambulatory care sensitive conditions (ACSC) by high ED utilizers in an urban safety net hospital. METHODS: High utilizers were defined as patients with ≥4 visits in the 6months before their most recent visit in the study period (July-December before and after Maryland's Medicaid expansion in January 2014). A differences-in-differences approach using logistic regression was used to investigate if differences between high and low utilizer cohorts changed from before and after the expansion. RESULTS: During the study period, 726 (4.1%) out of 17,795 unique patients in 2013 and 380 (2.4%) of 16,458 during the same period in 2014 were high utilizers (p-value <0.001). ACSC-associated visit predicted being a high utilizer in 2013 (OR 1.66 (95% CI [1.37, 2.01])) and 2014 (OR 1.65 (95% CI [1.27, 2.15])) but this was not different between years (OR ratio 0.99, 95% CI [0.72, 1.38], p-value 0.97). CONCLUSION: Although the proportion of high utilizers decreased significantly after Maryland's Medicaid expansion, ACSC-associated ED visits by high ED utilizers were unaffected.

A Comprehensive Framework for International Medical Programs: A 2017 consensus statement from the American College of Academic International Medicine.

The American College of Academic International Medicine (ACAIM) represents a group of clinicians who seek to promote clinical, educational, and scientific collaboration in the area of Academic International Medicine (AIM) to address health care disparities and improve patient care and outcomes globally. Significant health care delivery and quality gaps persist between high-income countries (HICs) and low-and-middle-income countries (LMICs). International Medical Programs (IMPs) are an important mechanism for addressing these inequalities. IMPs are international partnerships that primarily use education and training-based interventions to build sustainable clinical capacity. Within this overall context, a comprehensive framework for IMPs (CFIMPs) is needed to assist HICs and LMICs navigate the development of IMPs. The aim of this consensus statement is to highlight best practices and engage the global community in ACAIM's mission. Through this work, we highlight key aspects of IMPs including: (1) the structure; (2) core principles for successful and ethical development; (3) information technology; (4) medical education and training; (5) research and scientific investigation; and (6) program durability. The ultimate goal of current initiatives is to create a foundation upon which ACAIM and other organizations can begin to formalize a truly global network of clinical education/training and care delivery sites, with long-term sustainability as the primary pillar of international inter-institutional collaborations.

Evolving from academic to academic entrepreneur: overcoming barriers to scientific progress and finance.

The overall goal of my career as an academic chemist has always been the design and creation of advanced therapeutics and diagnostics that address unmet medical need in the management of chronic diseases. Realising this goal has been an immensely difficult process involving multidisciplinary problem-driven research at the chemistry-biology-medicine interfaces. With success in the laboratory, I started seriously to question the value of remaining an academic whose career is spent in the pursuit of knowledge and understanding alone without making any significant effort to translate knowledge and understanding gained into products of genuine utility for public benefit. Therefore, I elected by choice to become an academic entrepreneur, seeking opportunities wherever possible for the translation of the best of my personal and collaborative academic research work into potentially valuable and useful products. This choice has brought with it many unexpected difficulties and challenges. Nevertheless, progress bas been made and sufficient learnt to suggest that this would be an appropriate moment to take stock and provide some personal reflections on what it takes to design and create advanced therapeutics and diagnostics in the laboratory then seek to develop, innovate and translate the best towards market.

Advancing Environmental Flow Science: Developing Frameworks for Altered Landscapes and Integrating Efforts Across Disciplines.

Environmental flows represent a legal mechanism to balance existing and future water uses and sustain non-use values. Here, we identify current challenges, provide examples where they are important, and suggest research advances that would benefit environmental flow science. Specifically, environmental flow science would benefit by (1) developing approaches to address streamflow needs in highly modified landscapes where historic flows do not provide reasonable comparisons, (2) integrating water quality needs where interactions are apparent with quantity but not necessarily the proximate factor of the ecological degradation, especially as frequency and magnitudes of inflows to bays and estuaries, (3) providing a better understanding of the ecological needs of native species to offset the often unintended consequences of benefiting non-native species or their impact on flows, (4) improving our understanding of the non-use economic value to balance consumptive economic values, and (5) increasing our understanding of the stakeholder socioeconomic spatial distribution of attitudes and perceptions across the landscape. Environmental flow science is still an emerging interdisciplinary field and by integrating socioeconomic disciplines and developing new frameworks to accommodate our altered landscapes, we should help advance environmental flow science and likely increase successful implementation of flow standards.