An Open-Source Tool for Automated Human-Level Circling Behavior Detection.

Quantifying behavior and relating it to underlying biological states is of paramount importance in many life science fields. Although barriers to recording postural data have been reduced by progress in deep-learning-based computer vision tools for keypoint tracking, extracting specific behaviors from this data remains challenging. Manual behavior coding, the present gold standard, is labor-intensive and subject to intra- and inter-observer variability. Automatic methods are stymied by the difficulty of explicitly defining complex behaviors, even ones which appear obvious to the human eye. Here, we demonstrate an effective technique for detecting one such behavior, a form of locomotion characterized by stereotyped spinning, termed 'circling'. Though circling has an extensive history as a behavioral marker, at present there exists no standard automated detection method. Accordingly, we developed a technique to identify instances of the behavior by applying simple postprocessing to markerless keypoint data from videos of freely-exploring (Cib2-/-;Cib3-/-) mutant mice, a strain we previously found to exhibit circling. Our technique agrees with human consensus at the same level as do individual observers, and it achieves >90% accuracy in discriminating videos of wild type mice from videos of mutants. As using this technique requires no experience writing or modifying code, it also provides a convenient, noninvasive, quantitative tool for analyzing circling mouse models. Additionally, as our approach was agnostic to the underlying behavior, these results support the feasibility of algorithmically detecting specific, research-relevant behaviors using readily-interpretable parameters tuned on the basis of human consensus.

Robust Institutional Support and Collaboration Between Summer Training Programs in Cancer and Biomedicine Drive the Pivot to a Virtual Format in Response to the COVID Pandemic.

Summer internships serve important roles in training the next generation of biomedical researchers and healthcare providers through laboratory and clinical experiences that excite trainees about these fields and help them make informed decisions about career paths. The SARS-CoV-2 (COVID) pandemic and associated physical distancing restrictions precluded implementation of traditional in-person summer curricula and led to the cancellation of many internships across the USA. COVID-related disruptions also created opportunities for trainees to engage in remote research, become proficient in online learning platforms, and explore multidisciplinary topics. These skills are highly relevant to trainees as virtual interfaces occupy an increasingly mainstream role in their professional paths. The response to the COVID pandemic required real-time adaptations at all levels for major biomedical institutions including the University of Maryland Baltimore (UMB). Pivoting summer programs to a virtual format as part of this response provided a "teachable moment" to expose trainees to the innovation and resilience that are essential components of the biomedical profession. UMB summer programs, which span diverse biomedical disciplines from cancer research to diabetes, consolidated resources and identified mentors with online research projects to develop a robust virtual curriculum. Herein, data from a cancer-focused internship illustrate the collaborative adaptations to established components and creation of new learning modules in the transition to, and implementation of, online training. Outcomes are presented in the context of the COVID pandemic and significant societal issues that arose in the summer of 2020. The utility of virtual components and their impact on future programs is discussed.

Upscaling e-mental health in Europe: a six-country qualitative analysis and policy recommendations from the eMEN project.

E-mental health (eMH) encompasses the use of digital technologies to deliver, support, or enhance mental health services. Despite the growing evidence for the effectiveness of eMH interventions, the process of implementation of eMH solutions in healthcare remains slow throughout Europe. To address this issue, the e-Mental Health Innovation and Transnational Implementation Platform North-West Europe (eMEN) project was initiated to increase the dissemination and quality of eMH services in Europe. In this project, status analyses regarding eMH in the six participating countries (i.e., Belgium, France, Germany, Ireland, The Netherlands, and the UK) were conducted and eight recommendations for eMH were developed. Expert teams from the six participating countries conducted status analyses regarding the uptake of eMH based on a narrative literature review and stakeholder interviews. Based on these status analyses, the eMEN consortium developed eight policy recommendations to further support the implementation of eMH in Europe. The status analyses showed that the participating countries are in different stages of implementing eMH into mental healthcare. Some barriers to implementing eMH were common among countries (e.g., a limited legal and regulatory framework), while others were country-specific (e.g., fragmented, federal policies). The policy recommendations included fostering awareness, creating strong political commitment, and setting reliable standards related to ethics and data security. The eMEN project has provided the initial recommendations to guide political and regulatory processes regarding eMH. Further research is needed to establish well-tailored implementation strategies and to assess the generalizability of the recommendations beyond the countries involved in the eMEN project.

Two-Device Closure Method for Large Diameter Arteriotomies in Percutaneous Endovascular Aortic Repair.

BACKGROUND: Percutaneous endovascular aortic repairs (pEVARs) are associated with access site complications. Two-device technique using 2 Perclose devices has been well established. Combined Perclose and Angioseal technique has been described as well. We sought to determine whether a hybrid Perclose and Angioseal closure technique would safely and effectively establish hemostasis in large-bore arteriotomies up to 20F. METHODS: Patients were identified as candidates for percutaneous access based on preoperative computed tomography findings, perioperative ultrasound of femoral vessels, or a combination of the 2 modalities. Prior to sheath insertion, 1 Perclose device was predeployed. At the end of pEVAR, device sheath and introducer were withdrawn over a 0.035″ wire, and partially deployed Perclose was fully deployed. The sheath and introducer were fully withdrawn and the arteriotomy was closed with a 6F Angioseal vascular closure device and completion deployment of the Perclose. Patients were followed at day 1 and day 30 and at least 1 year postintervention. RESULTS: A composite end point of complications was defined as an access site-related bleed or hematoma that required blood transfusion or an extended hospital stay, pseudoaneurysm, arteriovenous fistula, dissection, or retroperitoneal hematoma. The combined technique was initially successful in 44/45 arteriotomies (97.8%) in 24/25 patients (96.0%) with no conversions to cutdown. Sheath sizes ranged from 10F to 20F outer diameter (OD), with an average of 15.89F OD. The single-device failure was caused by a failure of the footplate to catch during deployment in the Angioseal with a 20F arteriotomy. Consequently, that was the only patient in which this closure was attempted for an arteriotomy larger than 19F. There were no early or late complications in this series. CONCLUSIONS: Large-bore arteriotomies may be safely and effectively closed using a hybrid percutaneous closure technique for sheaths up to 19F OD. Evaluation of this technique in closure of large-bore arteriotomies is ongoing and further investigation is needed to assess the value of this closure in 20F OD sheaths and above.

Evaluating sub-typing methods for pathogenic Yersinia enterocolitica to support outbreak investigations in New Zealand.

Incidence of human yersiniosis in New Zealand has increased between 2013 and 2017. For surveillance and outbreak investigations it is essential that an appropriate level of discrimination between pathogenic Yersinia enterocolitica isolates is provided, in order to support epidemiological linking of connected cases. Subtyping of 227 Y. enterocolitica isolates was performed using a range of different typing methods, including biotyping, serotyping and seven loci multiple-locus variable-number tandem-repeat analysis (MLVA). In addition, core genome single-nucleotide polymorphism (core SNP) analysis and multi-locus sequence typing were performed on a subset of 69 isolates. Sixty-seven different MLVA types were identified. One MLVA profile was associated with an outbreak in the Bay of Plenty region, supported by epidemiological data. Core SNP analysis showed that all the outbreak-related isolates clustered together. The subtyping and epidemiological evidence suggests that the outbreak of yersiniosis in the Bay of Plenty region between October and December 2016 could be attributed to a point source. However, subtyping results further suggest that the same clone was isolated from several regions between August 2016 and March 2017. Core SNP analysis and MLVA typing failed to differentiate between Y. enterocolitica biotype 2 and biotype 3. For this reason, we propose that these biotypes should be reported as a single type namely: Y. enterocolitica biotype 2/3 and that the serotype should be prioritised as an indicator of prevalence.

Removal of retrievable inferior vena cava filters before discharge: Is it associated with increased incidence of pulmonary embolism?

BACKGROUND: Severely injured trauma patients are at high risk of developing deep venous thrombosis and pulmonary emboli (PE), and may have contraindications to prophylactic or therapeutic anticoagulation. Retrievable inferior vena cava filters (rIVCFs) are used to act as a mechanical obstruction to prevent PE in high risk populations and those with deep venous thrombosis who cannot be anticoagulated. The removal rate of rIVCFs is variable in trauma centers, including our previous published rate of 50% to 89%/year. Indwelling filters carry a risk of significant morbidity and the success of retrieval decreases as the dwell time increases. We hypothesized that once patients could receive appropriate prophylactic or therapeutic anticoagulation, rIVCF could be removed before hospital discharge without impact on occurrence or recurrence of PE. METHODS: All trauma patients with rIVCF placed and removed between January 2006 and August 2018 were reviewed. We collected data from record review from admission to 6 months postfilter removal, including demographics, filter indication, filter type, dwell time, placement and removal complications, antithrombosis medications, location of venous thromboembolism, complications, and discharge disposition. Exposure of interest was timing of filter removal: before (BEF) or after hospital discharge (AFT). The outcome of interest was whether the patient had a documented PE within 6 months of filter removal. RESULTS: A total of 281 rIVCFs were placed, 218 were eligible for removal, 72.4% (158/218) were retrieved with 63% (100/158) removed before discharge. Mean filter duration was 26 days and 103 days for the before and after groups, respectively. No differences (p > 0.05) were noted in the distribution of demographic and clinical factors except for filter indication (venous thromboembolism indication, 95% in AFT vs. 74% in BEF, p = 0.0043). Postremoval PE rates were 0% BEF and 1% AFT (Fisher's exact test, p = 1.000). CONCLUSION: Our results suggest that removal of rIVCFs before discharge once patients are appropriately anticoagulated is a safe strategy to improve retrieval rates. LEVEL OF EVIDENCE: Therapeutic, level V.

Creation of Colonic Anastomosis in Mice.

Intestinal anastomoses are commonly performed in both elective and emergent operations. Even so, anastomotic leaks are a highly feared complications of colonic surgeries and can occur in up to 26% of surgical anastomoses, with mortality being up to 39% for patients with such a leak. Currently, there remains a paucity of data detailing the cellular mechanisms of anastomotic healing. Devising preventative strategies and treatment modalities for anastomotic leak could be greatly potentiated by a better understanding of appropriate anastomotic healing. A murine model is ideal as previous studies have shown that the murine anastomosis is the most clinically similar to the human case as compared with other animal models. We offer an easily reproducible murine model of colonic anastomosis in mice that will allow for further illustration of anastomotic healing.

Effectiveness of Workplace Interventions in Return-to-Work for Musculoskeletal, Pain-Related and Mental Health Conditions: An Update of the Evidence and Messages for Practitioners.

Purpose The objective of this systematic review was to synthesize evidence on the effectiveness of workplace-based return-to-work (RTW) interventions and work disability management (DM) interventions that assist workers with musculoskeletal (MSK) and pain-related conditions and mental health (MH) conditions with RTW. Methods We followed a systematic review process developed by the Institute for Work & Health and an adapted best evidence synthesis that ranked evidence as strong, moderate, limited, or insufficient. Results Seven electronic databases were searched from January 1990 until April 2015, yielding 8898 non-duplicate references. Evidence from 36 medium and high quality studies were synthesized on 12 different intervention categories across three broad domains: health-focused, service coordination, and work modification interventions. There was strong evidence that duration away from work from both MSK or pain-related conditions and MH conditions were significantly reduced by multi-domain interventions encompassing at least two of the three domains. There was moderate evidence that these multi-domain interventions had a positive impact on cost outcomes. There was strong evidence that cognitive behavioural therapy interventions that do not also include workplace modifications or service coordination components are not effective in helping workers with MH conditions in RTW. Evidence for the effectiveness of other single-domain interventions was mixed, with some studies reporting positive effects and others reporting no effects on lost time and work functioning. Conclusions While there is substantial research literature focused on RTW, there are only a small number of quality workplace-based RTW intervention studies that involve workers with MSK or pain-related conditions and MH conditions. We recommend implementing multi-domain interventions (i.e. with healthcare provision, service coordination, and work accommodation components) to help reduce lost time for MSK or pain-related conditions and MH conditions. Practitioners should also consider implementing these programs to help improve work functioning and reduce costs associated with work disability.

Effects of pulmonary rehabilitation on exercise capacity and disease impact in patients with chronic obstructive pulmonary disease and obesity.

OBJECTIVES: To explore the influence of obesity on outcomes of exercise capacity and disease impact in patients with chronic obstructive pulmonary disease (COPD) in response to pulmonary rehabilitation (PR) and to compare outcomes to those of normal weight and overweight counterparts. DESIGN: Secondary data analysis of clinical database. SETTING: St. James's Hospital, Dublin, Ireland. PARTICIPANTS: 155 participants with a primary diagnosis of COPD who completed a PR programme between 2012 and 2014. MAIN OUTCOME MEASURES: Exercise capacity evaluated using the Six Minute Walk Test (6MWT) and the COPD Assessment Test (CAT) evaluated disease impact. RESULTS: Walking distance in the 6MWT improved significantly [mean difference of 55m (95% CI: 42 to 68; p<0.001)] and similarly [F(2, 92)=1.434, p=0.24] across all BMI categories, although the level of improvement reached clinical significance in the normal/underweight and overweight categories only. Disease impact on the CAT score improved across all body mass index (BMI) classifications by 2.3 points (95% CI: 0.9 to 3.6; p<0.050) which reached clinical significance and did not vary across BMI categories [F(2, 80)=0.534, p=0.58]. CONCLUSION: Exercise capacity and self-report disease impact of individuals with COPD improved similarly in response to PR irrespective of BMI.

Operative management of acetabulum fractures in the obese patient: challenges and solutions.

In this review, we aim to increase our knowledge of the treatment of acetabular fractures in the obese patient population. The extremely high incidence of obesity in the USA is a looming health care concern that impacts aspects of health care in all medical specialties. There are specific concerns to the orthopedic surgeon when treating obese patients for acetabular fracture. Patients with body mass index ≥30 present particular challenges to the surgeon in terms of preexisting medical conditions, diagnostic imaging, and perioperative complications. Specifically, this patient population experiences worse functional outcomes and greater incidence of surgical site infection, intraoperative blood loss, deep venous thrombosis, post-traumatic osteoarthritis, heterotopic ossification, and increased hospital length of stay. These problems are further exacerbated in the morbidly obese, as a scaling effect exists between increasing body mass index and worsening complication profile. This is problematic given the current high incidence of morbid obesity in the USA and particularly worrisome in light of the projected increase in obesity rates for the future.

Physiology of central pathways.

The relative simplicity of the neural circuits that mediate vestibular reflexes is well suited for linking systems and cellular levels of analyses. Notably, a distinctive feature of the vestibular system is that neurons at the first central stage of sensory processing in the vestibular nuclei are premotor neurons; the same neurons that receive vestibular-nerve input also send direct projections to motor pathways. For example, the simplicity of the three-neuron pathway that mediates the vestibulo-ocular reflex leads to the generation of compensatory eye movements within ~5ms of a head movement. Similarly, relatively direct pathways between the labyrinth and spinal cord control vestibulospinal reflexes. A second distinctive feature of the vestibular system is that the first stage of central processing is strongly multimodal. This is because the vestibular nuclei receive inputs from a wide range of cortical, cerebellar, and other brainstem structures in addition to direct inputs from the vestibular nerve. Recent studies in alert animals have established how extravestibular signals shape these "simple" reflexes to meet the needs of current behavioral goal. Moreover, multimodal interactions at higher levels, such as the vestibular cerebellum, thalamus, and cortex, play a vital role in ensuring accurate self-motion and spatial orientation perception.

Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. PATIENTS AND METHODS: In a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with dasatinib 70 mg p.o. b.i.d. Response was assessed every 8 weeks using RECIST. RESULTS: Of 54 patients: 40 ACC, 14 non-ACC (1, ineligible excluded); M:F = 28 : 26, median age 56 years (range 20-82 years), ECOG performance status 0 : 1 : 2 = 24 : 28 : 2, prior radiation: 44, prior chemotherapy: 21. The most frequent adverse events (AEs) (as % of patients, worst grade 2 or higher) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (7%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), neutropenia (6%), and noncardiac chest pain (6%). No grade 4 AE occurred, 15 patients experienced a grade 3 AE, primarily dyspnea (5) and fatigue (4), and cardiac toxicity (1 prolonged QTc). Among ACC patients, best response to dasatinib: 1 patient (2.5%) had partial response, 20 patients (50%) had stable disease (SD) (3-14 months), 12 patients (30%) had PD, 2 withdrew, 3 discontinued therapy due to AE, and 2 died before cycle 2. Median progression-free survival was 4.8 months. Median overall survival was 14.5 months. For 14 assessable non-ACC patients, none had objective response, triggering early stopping rule. Seven had SD (range 1-7 months), 4 PD, 2 discontinued therapy due to AE, and 1 died before cycle 2. CONCLUSION: Although there was only one objective response, dasatinib is well tolerated, with tumor stabilization achieved by 50% of ACC patients. Dasatinib demonstrated no activity in non-ACC MSGT.

Prevención de síntomas visuales y músculo-esqueléticos asociados al uso de ordenador en el trabajo / Workplace interventions to prevent musculoskeletal and visual symptoms and disorders among computer users: A systematic review

Antecedentes: La literatura científica sobre el efecto de las intervenciones en el puesto de trabajo, en la compensación de un defecto refractivo y en la conducta sobre los síntomas músculo-esqueléticos y visuales en los usuarios de ordenador, es amplia y heterogénea. Método: Se realizó una revisión sistemática de la literatura como la mejor síntesis de la evidencia para abordar la siguiente cuestión general: ¿Tienen las intervenciones en trabajadores de oficina que son usuarios de ordenador un efecto sobre la salud músculo-esquelética o visual? También se realizó una evaluación de intervenciones específicas. Resultados: La búsqueda inicial identificó 7.313 artículos que se redujeron a 31 estudios tras analizar contenido y calidad. En general, se observó un nivel mixto de evidencia para la pregunta general. Se observó una evidencia moderada de que: (1) la adaptación de los puestos de trabajo no tenía ningún efecto, (2) tampoco la realización de descansos y ejercicio y (3) utilizar dispositivos alternativos a los ratones convencionales sí tenía un efecto positivo. Para el resto de intervenciones se observó una evidencia del efecto mixta o insuficiente. Conclusión: Se encontraron pocos estudios de alta calidad que examinaran los efectos de las intervenciones en oficinas sobre los problemas musculo-esqueléticos y de la salud visual

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Going into the groin: Injection into the femoral vein among people who inject drugs in three urban areas of England.

BACKGROUND: There have been increasing concerns about injection into the femoral vein - groin injecting - among people who inject drugs in a number of countries, though most studies have been small. The extent, reasons and harms associated with groin injecting are examined. METHOD: Participants were recruited using respondent driven sampling (2006-2009). Weighted data was examined using bivariate analyses and logistic regression. RESULTS: The mean age was 32 years; 25% were women (N=855). During the preceding 28 days, 94% had injected heroin and 13% shared needles/syringes. Overall, 53% reported ever groin injecting, with 9.8% first doing so at the same age as starting to inject. Common reasons given for groin injecting included: "Can't get a vein elsewhere" (68%); "It is discreet" (18%); and "It is quicker" (14%). During the preceding 28 days, 41% had groin injected, for 77% this was the only body area used (for these "It is discreet" was more frequently given as a reason). In the multivariable analysis, groin injection was associated with: swabbing injection sites; saving filters for reuse; and receiving opiate substitution therapy. It was less common among those injecting into two body areas, and when other people (rather than services) were the main source of needles. Groin injection was more common among those with hepatitis C and reporting ever having deep vein thrombosis or septicaemia. CONCLUSIONS: Groin injection was common, often due to poor vascular access, but for some it was out of choice. Interventions are required to reduce injecting risk and this practice.

Potential roles of cytokines and chemokines in human intervertebral disc degeneration: interleukin-1 is a master regulator of catabolic processes.

OBJECTIVE: These studies investigated cytokine and chemokine receptor profiles in nucleus pulposus (NP) cells, and the effects of receptor stimulation on mRNA levels of extracellular matrix (ECM) components, degrading enzymes and cytokine and chemokine expression. METHOD: Immunohistochemistry (IHC) was performed to localise expression of CD4, CCR1, CXCR1 and CXCR2 in human NP tissue samples. Effects of cytokine and chemokine stimulation was performed to investigate effects related to ECM remodelling and modulation of cytokine and chemokine mRNA expression. RESULTS: IHC identified CD4, CCR1, CXCR1 and CXCR2 expression by NP cells. Differential expression profiles were observed for CD4 and CXCR2 in tissue samples from degenerate and infiltrated IVDs. In vitro stimulations of primary human NP cultures with IL-16, CCL2, CCL3, CCL7 or CXCL8 did not identify any modulatory effects on parameters associated with ECM remodelling or expression of other cytokines and chemokines. Conversely, IL-1 was seen to modulate ECM remodelling and expression of all other cytokines and chemokines investigated. CONCLUSION: This study demonstrates for the first time that NP cells express a number of cytokine and chemokine receptors and thus could respond in an autocrine or paracrine manner to cytokines and chemokines produced by NP cells, particularly during tissue degeneration. However, this study failed to demonstrate regulatory effects on ECM genes and degradative enzymes or other cytokines and chemokines for any target investigated, with the exception of IL-1. This suggests that IL-1 is a master regulator within the IVD and may exert regulatory potential over a plethora of other cytokines and chemokines.

Factors associated with recently acquired hepatitis C virus infection in people who inject drugs in England, Wales and Northern Ireland: new findings from an unlinked anonymous monitoring survey.

Monitoring infections and risk in people who inject drugs (PWID) is important for informing public health responses. In 2011, a novel hepatitis C antibody (anti-HCV) avidity-testing algorithm to identify samples compatible with recent primary infection was introduced into a national surveillance survey. PWID are recruited annually, through >60 needle-and-syringe programmes and prescribing services. Of the 980 individuals that could have been at risk of HCV infection, there were 20 (2%) samples that were compatible with recent primary infection. These were more common among: those imprisoned ⩾5 times [8/213; adjusted odds ratio (aOR) 8·7, 95% confidence interval (CI) 2·04-37·03]; women (8/230; aOR 3·8, 95% CI 1·41-10·38); and those ever-infected with hepatitis B (5/56; aOR 6·25, 95% CI 2·12-18·43). This study is the first to apply this algorithm and to examine the risk factors associated with recently acquired HCV infection in a national sample of PWID in the UK. These findings highlight underlying risks and suggest targeted interventions are needed.

Development and pilot testing of an online intervention to support young couples' coping and adjustment to breast cancer.

Couplelinks is an original, professionally facilitated online intervention tailored to the unique challenges facing young women with breast cancer and their male partners. The purpose of this evaluation was to determine the feasibility and acceptability of the intervention and areas for improvement. Sixteen couples were sequentially enrolled over an 18-month period. Couples provided feedback via a treatment satisfaction survey, and post-treatment interviews with a sub-group of participants. Qualitative information was analysed for themes relevant to the program's acceptability, perceived benefits and limitations, and directions for improvement. Of the 16 couples who enrolled, six completed four modules or less, and 10 completed the entire program. Completers reported satisfaction with the program overall, as well as with the website useability and professional facilitation. Reported benefits were: enhanced communication and self-other knowledge; creation of opportunities for meaningful, cancer-related discussion; affirmation of relationship strengths; and a greater sense of closeness between partners. The main reported limitation was how program participation disrupted the couple's usual routine. Themes related to non-completion suggest that partners with particularly elevated relational or illness-related distress, or with differential levels of motivation, are less likely to finish. These findings have led to targeted improvements to the website and intervention protocol.