Gastrointestinal dysmotility complicating Behçet's syndrome: description of a newly recognised clinical phenotype.

OBJECTIVES: Gastrointestinal dysmotility may arise in a variety of auto-immune and auto-inflammatory diseases and hitherto has not been described in Behçet's syndrome (BS). METHODS: We present data on a cohort of seven patients under our care who presented with symptoms of and investigations compatible with an immune associated disorder of gastrointestinal motility, or enteric neuropathy. RESULTS: We describe the clinical features and investigation results. We undertook a trial of a novel treatment in the disease, apheresis, and noted a response not only to the enteric neuropathy but also to the systemic features of the disease, despite previous maximal immunosuppressive therapy in most cases. CONCLUSIONS: Gastrointestinal dysmotility may arise in BS and is effectively treated by apheresis. The mechanism by which this response is made immunologically requires to be elucidated in future studies.

A method for comparing multiple imputation techniques: A case study on the U.S. national COVID cohort collaborative.

Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful for assessing associations between patients' predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases, whose removal may introduce severe bias. Several multiple imputation algorithms have been proposed to attempt to recover the missing information under an assumed missingness mechanism. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithm works best in a given scenario. Furthermore, the selection of each algorithm's parameters and data-related modeling choices are also both crucial and challenging. In this paper we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. Extensive experiments show that our approach can effectively highlight the most promising and performant missing-data handling strategy for our case study. Moreover, our methodology allowed a better understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types.

A Successful Collaboration Between an Urban School District, a Health System, and a Public Health Department to Address COVID-19 While Returning Children to the Classroom.

We sought to create and implement a set of COVID-19 mitigation processes including reliable testing to minimize in-school transmission of SARS-CoV-2. A large urban school district (> 33,000 students), a city health department, and a free-standing children's hospital partnered to implement multi-layered mitigation procedures which included access to polymerase chain reaction (PCR) testing with same day or next morning results. We tracked COVID-19 cases as well as probable/confirmed transmissions and identified needed mitigations through frequent huddles. During the 2020-2021 school year, there were 13 weeks of hybrid in person learning and 9 weeks of 5 day a week learning. Of the 1936 cases documented, only 3.2% resulted in subsequent school-related transmission. When children felt ill in the classroom, they were isolated within 10 min of reporting ill symptoms (> 90% of the time). PCR test results were routinely available to the school district by 6AM the following morning (79-99% of the time, depending on the learning model). An adaptive, fast-learning partnership across school district, public health, and a children's hospital minimized school-related transmission of COVID-19 and allowed children to safely return to the classroom.

Human Support in App-Based Cognitive Behavioral Therapies for Emotional Disorders: Scoping Review.

BACKGROUND: Smartphone app-based therapies offer clear promise for reducing the gap in available mental health care for people at risk for or people with mental illness. To this end, as smartphone ownership has become widespread, app-based therapies have become increasingly common. However, the research on app-based therapies is lagging behind. In particular, although experts suggest that human support may be critical for increasing engagement and effectiveness, we have little systematic knowledge about the role that human support plays in app-based therapy. It is critical to address these open questions to optimally design and scale these interventions. OBJECTIVE: The purpose of this study is to provide a scoping review of the use of human support or coaching in app-based cognitive behavioral therapy for emotional disorders, identify critical knowledge gaps, and offer recommendations for future research. Cognitive behavioral therapy is the most well-researched treatment for a wide range of concerns and is understood to be particularly well suited to digital implementations, given its structured, skill-based approach. METHODS: We conducted systematic searches of 3 databases (PubMed, PsycINFO, and Embase). Broadly, eligible articles described a cognitive behavioral intervention delivered via smartphone app whose primary target was an emotional disorder or problem and included some level of human involvement or support (coaching). All records were reviewed by 2 authors. Information regarding the qualifications and training of coaches, stated purpose and content of the coaching, method and frequency of communication with users, and relationship between coaching and outcomes was recorded. RESULTS: Of the 2940 titles returned by the searches, 64 (2.18%) were eligible for inclusion. This review found significant heterogeneity across all of the dimensions of coaching considered as well as considerable missing information in the published articles. Moreover, few studies had qualitatively or quantitatively evaluated how the level of coaching impacts treatment engagement or outcomes. Although users tend to self-report that coaching improves their engagement and outcomes, there is limited and mixed supporting quantitative evidence at present. CONCLUSIONS: Digital mental health is a young but rapidly expanding field with great potential to improve the reach of evidence-based care. Researchers across the reviewed articles offered numerous approaches to encouraging and guiding users. However, with the relative infancy of these treatment approaches, this review found that the field has yet to develop standards or consensus for implementing coaching protocols, let alone those for measuring and reporting on the impact. We conclude that coaching remains a significant hole in the growing digital mental health literature and lay out recommendations for future data collection, reporting, experimentation, and analysis.

What's suffering got to do with it? A qualitative study of suffering in the context of Medical Assistance in Dying (MAID).

BACKGROUND: Intolerable suffering is a common eligibility requirement for persons requesting assisted death, and although suffering has received philosophic attention for millennia, only recently has it been the focus of empirical inquiry. Robust theoretical knowledge about suffering is critically important as modern healthcare provides persons with different options at end-of-life to relieve suffering. The purpose of this paper is to present findings specific to the understanding and application of suffering in the context of MAID from nurses' perspectives. METHODS: A longitudinal qualitative descriptive study using semi-structured telephone interviews. Inductive analysis was used to construct a thematic account. The study received ethical approval and all participants provided written consent. RESULTS: Fifty nurses and nurse practitioners from across Canada were interviewed. Participants described the suffering of dying and provided insights into the difficulties of treating existential suffering and the iatrogenic suffering patients experienced from long contact with the healthcare system. They shared perceptions of the suffering that leads to a request for MAID that included the unknown of dying, a desire for predictability, and the loss of dignity. Eliciting the suffering story was an essential part of nursing practice. Knowledge of the story allowed participants to find the balance between believing that suffering is whatever the persons says it is, while making sure that the MAID procedure was for the right person, for the right reason, at the right time. Participants perceived that the MAID process itself caused suffering that resulted from the complexity of decision-making, the chances of being deemed ineligible, and the heighted work of the tasks of dying. CONCLUSIONS: Healthcare providers involved in MAID must be critically reflective about the suffering histories they bring to the clinical encounter, particularly iatrogenic suffering. Further, eliciting the suffering stories of persons requesting MAID requires a high degree of skill; those involved in the assessment process must have the time and competency to do this important role well. The nature of suffering that patients and family encounter as they enter the contemplation, assessment, and provision of MAID requires further research to understand it better and develop best practices.

Extraocular muscle architecture in hawks and owls.

OBJECTIVE: A complete and accurate understanding of extraocular muscle function is important to the veterinary care of the avian eye. This is especially true for birds of prey, which rely heavily on vision for survival and yet are prone to ocular injury and disease. To better understand the function of extraocular muscles in birds of prey, we studied extraocular muscle architecture grossly and histologically. ANIMALS STUDIED: This sample was composed of two each of the following species: red-tailed hawk (Buteo jamaicensis), Harris's hawk (Parabuteo unicinctus), great horned owl (Bubo virginianus), and barn owl (Tyto alba). PROCEDURES: All extraocular muscles were dissected and weighed. To analyze muscle fiber architecture, the superior oblique and quadratus muscles were dissected, weighed, and sectioned at 5 µm thickness in the transverse plane. We calculated the physiologic cross-sectional area and the ratio of muscle mass to predicted effective maximum tetanic tension. RESULTS AND CONCLUSIONS: Hawk and owl extraocular muscles exhibit significant physiological differences that play roles in ocular movements and closure of the nictitating membrane. Owls, which do not exhibit extraocular movement, have muscle architecture suited to stabilize the position of a massive, tubular eye that protrudes significantly from the orbit. Hawks, which have a more globose eye that is largely contained within the orbit, do not require as much muscular stability and instead have muscle architecture that facilitates rapid eye movement.

Grossly Abnormal Ventilation/Perfusion SPECT Study in Idiopathic Pulmonary Arterial Hypertension Without Thromboembolism.

Pulmonary hypertension is a serious condition with multiple underlying aetiologies which require different treatment strategies. We present a case of severe idiopathic pulmonary arterial hypertension in a 20-year-old patient with ongoing breathlessness. She was initially diagnosed with asthma and panic attacks in community care. As the symptoms became progressively worse, she was referred for pulmonary hypertension clinic assessment. Ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) showed grossly abnormal perfusion defects which were mismatched to the ventilation scan, suggestive of chronic thromboembolic disease. However, corroborating computed tomographic (CT) pulmonary angiogram and invasive pulmonary angiography showed no thromboembolic disease. Histological examination of the pulmonary arteries post-mortem showed changes consistent with idiopathic pulmonary arterial hypertension. This case highlighted the clinical challenges in interpreting the investigation results and phenotyping pulmonary hypertension. V/Q SPECT might have a role in visualising the extent of vasculopathies in pulmonary arterial hypertension.

A functional and clinical reinterpretation of human perineal neuromuscular anatomy: Application to sexual function and continence.

Modern anatomical and surgical references illustrate perineal muscles all innervated by branches of the pudendal nerve but still organized into anatomically distinct urogenital and anal triangles with muscles inserting onto a central perineal body. However, these conflict with the anatomy commonly encountered during dissection. We used dissections of 43 human cadavers to characterize the anatomical organization of the human perineum and compare our findings to standard references. We found bulbospongiosus and the superficial portion of the external anal sphincter (EAS) were continuous anatomically with a common innervation in 92.3% of specimens. The superficial transverse perineal muscle inserted anterior and lateral to the midline, interdigitating with bulbospongiosus. The three EAS subdivisions were anatomically discontinuous. Additionally, in 89.2% of our sample the inferior rectal nerve emerged as a branch of S3 and S4 distinct from the pudendal nerve and innervated only the subcutaneous EAS. Branches of the perineal nerve innervated bulbospongiosus and the superficial EAS and nerve to levator ani innervated the deep EAS. In conclusion, we empirically demonstrate important and clinically relevant differences with perineal anatomy commonly described in standard texts. First, independent innervation to the three portions of EAS suggests the potential for functional independence. Second, neuromuscular continuity between bulbospongiosus and superficial EAS suggests the possibility of shared or overlapping function of the urogenital and anal triangles. Clin. Anat. 29:1053-1058, 2016. © 2016 Wiley Periodicals, Inc.

The Evolving Complexities of MAID Care in Canada From a Nursing Perspective.

Medical Assistance in Dying (MAID) legislation has evolved rapidly in Canada with significant impacts on nursing practice. The purpose of this paper is to describe evolving complexities in legislative context and practice standards that influence the experiences nurse practitioners and registered nurses have with MAID. Qualitative interviews were conducted with 25 registered nurses and 10 nurse practitioners from diverse contexts across Canada. Participants described their practices and considerations when discussing MAID as part of advance care planning; their use of, and challenges with, waivers of consent; their practice considerations in negotiating the complexities of clients for whom death is not reasonably foreseeable; and their moral wrestling with the inclusion of MAID for persons whose sole underlying medical condition is mental illness. Findings illustrate the moral complexities inherent in the evolving legislation and the importance of robust health and social care systems to the legal and ethical implementation of MAID in Canada.

Time to Response in Therapy for Body Dysmorphic Disorder: A Comparison of Cognitive Behavioral Therapy and Supportive Psychotherapy.

Psychotherapy has been shown to be effective for individuals with body dysmorphic disorder (BDD); however, time to treatment response for different treatments have not yet been examined. We randomized 120 patients to either weekly cognitive behavioral therapy (CBT) or supportive psychotherapy (SPT) at two academic medical research centers. In this secondary data analysis, we aimed to determine the time to first response (30% or greater reduction in BDD symptom severity) in both treatment conditions among those who attended at least one post-baseline assessment (n = 109). As previously reported, CBT for BDD was associated with more consistent improvement in symptom severity and quality of life than SPT. In a pooled analysis combining both sites, the median time to first response was shorter for CBT (76 days [10.9 weeks], 95% CI: 76-107 days) than for SPT (88 days [12.6 weeks], 95% CI: 88-nonestimable days; Χ2df=1 = 3.85, p = .0498). For CBT, the estimated 75th percentile response times were 148 days [21.1 weeks] at site 1 and 134 days [19.1 weeks] at site 2. Response times were not estimable for SPT at either site because the response rate was too low. Thus, therapy clients seeking treatment for BDD and clinicians should be aware that an initial treatment response requires more than 11 therapy sessions for the majority of clients, and that 21 or even more sessions may be required. Treatment response is likely to occur earlier with CBT for BDD (the first-line therapy for BDD) than with supportive psychotherapy.

Exploring the patient experience and perspectives of taking part in outcome measurement during lower limb prosthetic rehabilitation: a qualitative study.

PURPOSE: Outcome measurement provides clinicians, services and funders with useful information. However, little is known about the experience of participating in outcome measurement during lower limb prosthetic rehabilitation from the patient's perspective. MATERIALS AND METHODS: Thirty-two participants who underwent lower limb amputation within 5 years, and had experience of taking part in outcome measurement during prosthetic rehabilitation, were recruited from UK limb fitting centers and social media. Data were collected using focus groups and interviews and analysed using reflexive thematic analysis. RESULTS: Four themes were identified. (1) How does participating in outcome measurement make me feel? (2) Do the outcome measures used in routine clinical care capture an accurate picture of my recovery? (3) Who is outcome measurement for? and (4) are prosthetic services measuring what is meaningful? These themes suggest outcome measurement is not a neutral activity for patients following lower limb amputation. CONCLUSIONS: Harnessing the positive impacts of measuring outcomes could be used for motivation, to support adjustment and recovery, to improve communication and to support shared decision-making. This could make outcome measurement more meaningful and patient-centered. However, there may be potential for patients to respond negatively to outcome measures and clinicians should consider their impact on psychosocial factors.

Outcome measurement in prosthetic rehabilitation can provide clinicians, service providers and funders with important information.Adopting a patient-centred approach could make the process more meaningful and therefore beneficial for patients themselves.Measuring what is important to patients by considering a holistic approach beyond physical domains may make outcome measurement more meaningful.Patient centred approaches may include talking to patients about outcome measurement, using it to support motivation, goal setting and decision-making, as well as exploring outcome ranges to account for, or even capture variability.However, the potential for negative responses should not be overlooked, and clinicians should consider the psychosocial impact of outcome measurement on this patient group, especially when using performance-based measures.

A reinterpretation of human breast anatomy includes all the layers of the anterior body wall.

Mammary glands define mammals as a group, yet a comprehensive anatomical description of the mammary gland does not exist for almost any mammalian species. In humans, the anatomical and surgical literature provide conflicting and incomplete descriptions of the gross anatomy of the breast. We dissected 9 male and 15 female human body donors to clarify this gross anatomy. We found that, like other epidermally derived glands of the body, the mammary glandular tissue is constrained to a membrane-bound, central structure referred to as the corpus mammae in the surgical literature, and not dispersed throughout the breast as typically described in the anatomical literature. The major fasciae of the human anterior body wall, including the superficial fatty Camper's fascia and the deeper membranous Scarpa's fascia, both contribute to the structure of the breast. This anatomical arrangement suggests that, as the mammary gland invaginates posteriorly from the integument during embryological development, the mammary fat pad most likely derives from Camper's fascia, and growth of Scarpa's fascia around this fat pad forms the anterior and posterior lamellae of the breast pocket. Anteriorly, Scarpa's fascia becomes a double layer that creates the surface structure of the breast. Posteriorly, Scarpa's fascia forms a circummammary ligament that (1) stabilizes the breast against the thoracic wall and (2) is continuous with Scarpa's fascia on the rest of the anterior body wall. The suspensory ligaments of the breast represent the typical retinaculae cuti found consistently throughout the human body wall, and do not directly attach to the skin. Instead, these retinaculae attach to the anterior or posterior lamella of Scarpa's fascia.

Clinically relevant orthotopic pancreatic cancer models for adoptive T cell transfer therapy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor. Prognosis is poor and survival is low in patients diagnosed with this disease, with a survival rate of ~12% at 5 years. Immunotherapy, including adoptive T cell transfer therapy, has not impacted the outcomes in patients with PDAC, due in part to the hostile tumor microenvironment (TME) which limits T cell trafficking and persistence. We posit that murine models serve as useful tools to study the fate of T cell therapy. Currently, genetically engineered mouse models (GEMMs) for PDAC are considered a "gold-standard" as they recapitulate many aspects of human disease. However, these models have limitations, including marked tumor variability across individual mice and the cost of colony maintenance. METHODS: Using flow cytometry and immunohistochemistry, we characterized the immunological features and trafficking patterns of adoptively transferred T cells in orthotopic PDAC (C57BL/6) models using two mouse cell lines, KPC-Luc and MT-5, isolated from C57BL/6 KPC-GEMM (KrasLSL-G12D/+p53-/- and KrasLSL-G12D/+p53LSL-R172H/+, respectively). RESULTS: The MT-5 orthotopic model best recapitulates the cellular and stromal features of the TME in the PDAC GEMM. In contrast, far more host immune cells infiltrate the KPC-Luc tumors, which have less stroma, although CD4+ and CD8+ T cells were similarly detected in the MT-5 tumors compared with KPC-GEMM in mice. Interestingly, we found that chimeric antigen receptor (CAR) T cells redirected to recognize mesothelin on these tumors that signal via CD3ζ and 41BB (Meso-41BBζ-CAR T cells) infiltrated the tumors of mice bearing stroma-devoid KPC-Luc orthotopic tumors, but not MT-5 tumors. CONCLUSIONS: Our data establish for the first time a reproducible and realistic clinical system useful for modeling stroma-rich and stroma-devoid PDAC tumors. These models shall serve an indepth study of how to overcome barriers that limit antitumor activity of adoptively transferred T cells.

A scoping review of digital fabrication techniques applied to prosthetics and orthotics: Part 1 of 2-Prosthetics.

BACKGROUND: Traditionally, the manufacture of prostheses is time-consuming and labor-intensive. One possible route to improving access and quality of these devices is the digitalizing of the fabrication process, which may reduce the burden of manual labor and bring the potential for automation that could help unblock access to assistive technologies globally. OBJECTIVES: To identify where there are gaps in the literature that are creating barriers to decision-making on either appropriate uptake by clinical teams or on the needed next steps in research that mean these technologies can continue on a pathway to maturity. STUDY DESIGN: Scoping literature review. METHODS: A comprehensive search was completed in the following databases: Allied and Complementary Medicine Database, MEDLINE, Embase, Global Health Archive, CINAHL Plus, Cochrane Library, Web of Science, Association for Computing Machinery, Institute of Electrical and Electronics Engineers, and Engineering Village, resulting in 3487 articles to be screened. RESULTS: After screening, 130 lower limb prosthetic articles and 117 upper limb prosthetic articles were included in this review. Multiple limitations in the literature were identified, particularly a lack of long-term, larger-scale studies; research into the training requirements for these technologies and the necessary rectification processes; and a high range of variance of production workflows and materials which makes drawing conclusions difficult. CONCLUSIONS: These limitations create a barrier to adequate evidence-based decision-making for clinicians, technology developers, and wider policymakers. Increased collaboration between academia, industry, and clinical teams across more of the pathway to market for new technologies could be a route to addressing these gaps.

An alternate dissection approach to the female urogenital triangle.

Traditional dissections of the female urogenital (UG) triangle can lead to early destruction of the erectile tissues, associated musculature, and neurovascular structures. Here, we present an alternate dissection of the female UG triangle. Rather than begin the female UG triangle dissection with the fatty tissue of the labia majora, we utilize an early identification of the suspensory ligament of the clitoris to organize the dissection. The suspensory ligament leads to the body of the clitoris, which can be palpated from distal to proximal to find the crura of the clitoris with overlying ischiocavernosus muscles. Once the crura have been defined, the bulbs of the vestibule with overlying bulbospongiosus muscles can be palpated medially and posteriorly. This dissection approach results in a clean dissection that well demonstrates homologies between male and female external genitalia. Through the use of this method, most student dissection attempts are able to demonstrate the erectile tissues and associated musculature that comprise the female UG triangle. This technique can also be used for male UG triangle dissections, encouraging identification of male and female homologies.

Comparative anatomy of the felid brachial plexus reflects differing hunting strategies between Pantherinae (snow leopard, Panthera uncia) and Felinae (domestic cat, Felis catus).

The brachial plexus, a network of ventral rami providing somatic sensory and motor innervation to the forelimb, is of particular importance in felids. Large-bodied pantherines require powerful rotatory and joint stabilizing forelimb muscles to maintain secure holds on large prey, while smaller-bodied felines are small prey specialists reliant on manual dexterity. Brachial plexus dissections of two snow leopards (Panthera uncia) and two domestic cats (Felis catus) revealed that generally the morphology of the brachial plexus is quite conserved. However, differences in the nerves supplying the shoulder and antebrachium may reflect differing prey capture strategies between the subfamilies. The brachial plexus of both species derives from ventral rami of C6-T1. In P. uncia, an extensive musculus (m.) subscapularis with multiple pennations is innervated by a larger number of nn. subscapulares, deriving from more spinal cord levels than in F. catus. C6 continues to become n. suprascapularis in both taxa; however, in F. catus, it also gives branches that join with C7, while in P. uncia, it is dedicated to musculi (mm.) supraspinatus, infraspinatus, and a small branch to cervical musculature. In F. catus, nervus (n.) medianus receives direct contributions from more ventral rami than P. uncia, possibly reflecting a greater reliance on manual dexterity in prey capture in the former. In addition to primary innervation by n. thoracodorsalis, m. latissimus dorsi is also innervated by n. thoracicus lateralis near the axilla in both taxa, suggesting that it may belong to a complex of proximal forelimb musculature along with mm. pectoralis profundus and cutaneus trunci.

Exploring meaningful outcome domains of recovery following lower limb amputation and prosthetic rehabilitation: the patient's perspective.

PURPOSE: There is currently no consensus regarding what outcome domains to measure following lower limb prosthetic rehabilitation. Prosthetic users have a unique insight into important outcome domains, little is currently known about their critical viewpoint. MATERIALS AND METHODS: A total of 37 participants who underwent lower limb amputation in the last five years were recruited from UK limb fitting centres and social media. Data were collected using focus groups and interviews and analysed using reflexive thematic analysis. RESULTS: Five themes were identified. 1) The ability to participate in important activities, 2) how participants were able to undertake these activities, i.e., independently, with ease, safely and with minimal equipment. 3) A comfortable, easy-to-use prosthesis, 4) the importance of managing pain and finally, 5) adjusting and accepting their new normal. These five themes, or outcome domains, did not exist in isolation, but appeared to interact with each other, contributing to, or inhibiting the participant's holistic sense of recovery. CONCLUSIONS: Understanding important outcome domains that define what recovery means to people following amputation can help to inform domain consensus, as well as direct the focus of rehabilitation. Domain consensus would guide the selection of measurement tools that evaluate prosthetic interventions in a meaningful way.IMPLICATIONS FOR REHABILITATIONThere is currently no consensus around which outcome domains should be measured following prosthetic rehabilitation.Outcome domains of importance from a patient's perspective focus on participation in important activities, prosthesis comfort, pain management, and acceptance of their new normal.Identifying these domains can help direct the focus of rehabilitation as well as inform outcome measurement practice.The interrelated nature of these domains suggests the need for a physical and psychosocial multi-domain approach to outcome measurement in prosthetic rehabilitation, with patient priorities at its centre.

Modified Comprehensive Behavioral Intervention for Tics: Treating Children With Tic Disorders, Co-Occurring ADHD, and Psychosocial Impairment.

Our objective was to evaluate the feasibility and acceptability, and preliminary efficacy of a modified comprehensive behavioral intervention for tics (MCBIT) therapy for youth with chronic tic disorders (CTDs), co-occurring attention-deficit hyperactivity disorder (ADHD), and associated psychosocial impairment. Seventeen youth ages 10-17 with CTD and co-occurring ADHD were randomly assigned to the MCBIT group (n = 9) or to a control group where they received traditional comprehensive behavioral intervention for tics (CBIT) therapy (n = 8). Both groups received ten 55-minute weekly treatment sessions, and two 55-minute biweekly relapse prevention sessions. Sixteen of the 17 participants completed the study, and acceptability ratings in both treatment groups were high with no significant differences in expectation of improvement. The MCBIT and CBIT groups in combination showed significant improvement in tic severity, ADHD symptom severity, and tic-related impairment. Group differences were not significant. The results indicate that MCBIT treatment is feasible and acceptable for youth with CTD and ADHD, and is similarly well tolerated relative to traditional CBIT. Results were not sufficiently superior to recommend MCBIT over CBIT for this population. However, given the demonstrated benefit of behavioral treatments that target co-occurring conditions concurrently, continuing to examine novel behavioral approaches that can target tics and related conditions simultaneously and successfully is recommended.

FaStaNMF: a Fast and Stable Non-negative Matrix Factorization for Gene Expression.

Gene expression analysis of samples with mixed cell types only provides limited insight to the characteristics of specific tissues. In silico deconvolution can be applied to extract cell type specific expression, thus avoiding prohibitively expensive techniques such as cell sorting or single-cell sequencing. Non-negative matrix factorization (NMF) is a deconvolution method shown to be useful for gene expression data, in part due to its constraint of non-negativity. Unlike other methods, NMF provides the capability to deconvolve without prior knowledge of the components of the model. However, NMF is not guaranteed to provide a globally unique solution. In this work, we present FaStaNMF, a method that balances achieving global stability of the NMF results, which is essential for inter-experiment and inter-lab reproducibility, with accuracy and speed. Results: FaStaNMF was applied to four datasets with known ground truth, created based on publicly available data or by using our simulation infrastructure, RNAGinesis. We assessed FaStaNMF on three criteria - speed, accuracy, and stability, and it favorably compared to the standard approach of achieving reproduceable results with NMF. We expect that FaStaNMF can be applied successfully to a wide array of biological data, such as different tumor/immune and other disease microenvironments.

Footwear characteristics and foot problems in community dwelling people with stroke: a cross-sectional observational study.

PURPOSE: To explore footwear characteristics and foot problems in community dwelling people with stroke as most research to date focused on the general elderly population. METHODS: Thirty people with mild to moderate stroke (nine men, mean age 68, mean time since onset 67 months) attended a single session to assess footwear and foot problems using established podiatry foot (wear) and ankle assessments. RESULTS: Most participants wore slippers indoors (n = 17, 57%) and walking shoes outdoors (n = 11, 37%). Over half wore unsupportive ill-fitting shoes indoors and 47% of outdoor shoes fitted badly. All participants had foot problems (mean 6.5 (3.1), 95% CI: 5.4-7.7), including impaired single limb heel raise (93%), reduced range of movement (77%), sensation (47%), and muscle strength (43%). Many had foot-pain, hallux valgus (both 50%), or swollen feet (40%). Foot problems were associated with reduced balance confidence, activity, and community participation (all p < 0.05). A greater proportion of fallers (13/16) than non-fallers (4/14) reported foot problems (p = 0.029). CONCLUSIONS: Many community-dwelling people with stroke wore poorly fitting shoes; all had foot problems. Foot problems were linked to reduced mobility. Finding more effective pathways to support people with stroke to select supportive, well-fitting indoor and outdoor footwear is indicated.Implications for rehabilitationPeople with stroke often wear unsupportive ill-fitting shoes and experience foot problems.Assessment of foot problems and footwear advice should be considered during stroke rehabilitation particularly when interventions target fall prevention or improvements in balance and mobility.Information on appropriate footwear and signposting that new shoe purchases should include measuring feet to ensure a good fit is recommended.