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Objective Method Results Conclusions The coronavirus pandemic drastically increased social isolation. Autistic youth already experience elevated social isolation and loneliness, making them highly vulnerable to the impact of the pandemic. We examined trajectories of social disruption and loneliness in autistic and non-autistic youth during a six-month period of the pandemic (June 2020 until November 2020).Participants were 76 youth, ages 8 through 17, (Mage = 12.82, Nautistic = 51) with an IQ ≥ 70. Youth completed a biweekly measure of loneliness (Revised UCLA Loneliness Scale) and their parent completed a measure of pandemic-related family social disruption (Epidemic Pandemic Impacts Inventory).There were no time trends in loneliness across all youth, however, social disruption displayed linear, quadratic, and cubic trends. Non-autistic youth reported relatively greater declines in social disruption compared to autistic youth. Additionally, autistic youth reported relatively greater declines in loneliness relative to non-autistic youth. Greater social disruption was associated with higher loneliness, however, autistic youth demonstrated a relatively stronger relationship between social disruption and loneliness compared to non-autistic youth.The current study was one of the first to investigate social disruption and loneliness in autistic youth during the COVID-19 pandemic. Results indicated that autistic youth experienced relative decreases in loneliness during this time, perhaps due to reductions in social demands. Nonetheless, when autistic youth did experience social disruption, they reported relatively higher levels of loneliness. This work contributes to our understanding of risk factors for loneliness and highlights the need to understand the benefits, as well as the challenges, to remote schooling and social interactions. [ABSTRACT FROM AUTHOR]

Group social skills interventions (GSSIs) are among the most commonly used treatments for improving social competence in youth with ASD, however, results remain variable. The current study examined predictors of treatment response to an empirically-supported GSSI for youth with ASD delivered in the community (Ntotal=75). Participants completed a computer-based emotion recognition task and their parents completed measures of broad psychopathology, ASD symptomatology, and social skills. We utilized generalized estimating equations in an ANCOVA-of-change framework to account for nesting. Results indicate differential improvements in emotion recognition by sex as well as ADHD-specific improvements in adaptive functioning. Youth with both co-occurring anxiety and ADHD experienced iatrogenic effects, suggesting that SDARI may be most effective for youth with ASD without multiple co-occurring issues. Findings provide important directions for addressing variability in treatment outcomes for youth with ASD. [ABSTRACT FROM AUTHOR]

While social difficulties in autism are well‐established, questions remain regarding whether these represent challenges in acquiring or performing such skills, reduced social strengths, or a unique distribution across these domains (i.e., social profile). This study empirically derived social profiles of 211 autistic and non‐autistic youth (Mage = 13.50; Autistic N = 150; Male N = 151; 85.3% White). Assessments occurred between 2016 and 2020. Results showed that autistic youth exhibit significantly more social acquisition and performance deficits and fewer strengths than nonautistic youth (ds = −.44 to.65). Performance deficits were most—and acquisition deficits least—prominent within autistic profiles, potentially implicating longstanding theoretical models of social difficulties in autism, and supporting new, idiographic approaches for conceptualizing, assessing, and treating social challenges. [ABSTRACT FROM AUTHOR]

Autistic youth experience elevated rates of co-occurring internalizing symptoms. Interventions to treat internalizing symptoms in autistic youth are almost uniformly costly and time-intensive, blunting dissemination of intervention and highlighting the need for scalable solutions. One promising option is a relatively new class of evidence-based treatments, single-session interventions (SSIs), however, no study has examined SSIs for depression symptoms in autistic youth. Participants included 40 autistic adolescents ranging in age from 11 to 16 (Mage = 14.22, Nmale = 32). Eligible youth who agreed to participate were randomized to either the active intervention (Project Personality), or an active control designed to mimic supportive therapy. Participants and their caregiver completed questionnaires immediately before, after, and three months post intervention. All participants completed the intervention independently and largely reported enjoying it. The intervention was delivered with 100% fidelity. Findings demonstrated improvements in perceived primary control, malleability of personality, and social competence relative to the active control group immediately post-intervention. Further, results revealed improvements in self-reported depression symptoms and parent reported emotional regulation at 3-month follow up. This study was the first to assess a GM-SSI designed to treat depression symptoms in autistic adolescents. Results indicated improvements in perceived control immediately post-intervention and downstream improvements in depression. Nonetheless, we did not find improvements in symptoms of anxiety, suggesting that autistic adolescents may require modifications to the intervention to maximize benefit. Findings demonstrate the utility of GM-SSI for internalizing symptoms for autistic youth and hold considerable promise as a low-intensity and scalable intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Practice guidelines (CPGs) provide informed treatment recommendations from systematic reviews and assessment of the benefits and harms that are intended to optimize patient care. Review of CPGs addressing rehabilitation for people with moderate/severe traumatic brain injury (TBI), has not been fully investigated. OBJECTIVE: Identify published, vetted, clinical practice guidelines that address rehabilitation for people with moderate/severe TBI. METHODS: Six data bases were accessed using key word search terms: "Traumatic Brain Injury" and "Clinical Practice Guidelines" and "Rehabilitation". Further inclusions included "adult" and "moderate or severe". Exclusions included: "mild" and "concussive injury". Three reviewers read abstracts and manuscripts for final inclusion. The AGREE II template was applied for additional appraisal. RESULTS: There were 767 articles retrieved using the search terms, 520 were eliminated because of content irrelevance; and 157 did not specify rehabilitation treatment or did not follow a process for CPGs. A total of 17 CPGs met all criteria and only 4 of these met all AGREE II criteria. CONCLUSION: There are few CPGs addressing rehabilitation for people with moderate/severe TBI. More interventional trials are needed to determine treatment effectiveness. Timely and methodologically sound vetting of studies are needed to ensure CPG reliability and facilitate access to quality, effective treatment for people with moderate/severe TBI. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines provide reliable, vetted, and critical information to bring research to practice. Some medical specialties (e.g., physical medicine and rehabilitation) provide multidomain treatment for various conditions. This presents challenges because physical medicine and rehabilitation is a small specialty, a diverse patient base in terms sociodemographics and diagnosis, treatments are difficult to standardize, and rehabilitation research is underfunded. We wished to identify quality and applicability of clinical practice guidelines and searched "Spinal Cord Injury AND Clinical Practice Guidelines AND Rehabilitation" and vetting process. Three hundred fifty-nine articles were identified of which 58 met all criteria for full-text review of which 13 were included in the final selection. Additional publications were accessed from a nondatabase search. Five articles addressed postacute care, community treatment. Nine articles had no recorded vetting process but addressed rehabilitation as an outcome and were included separately. Many of the clinical practice guidelines were developed without evidence from randomized controlled trials, one had input from stakeholders, and some are out of date and do not address important aspects of changes in demographics of the affected population and the use of newer technologies such as sensors and robotics and devices. Identification of these gaps may help stimulate treatment that is clinically relevant, accessible, and current. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines (CPGs) provide an efficient route from research to practice because they follow a prescribed, vetted process for evidence collection. CPGs offer underserved fields, such as burn rehabilitation, an accessible approach to reliable treatment. A literature search was performed using the terms "Burns AND CPGs AND Rehabilitation." Three reviewers determined whether guideline development followed an established vetting process. "Rehabilitation" required evidence of treatment to improve, maintain, or restore human function and provide treatment to facilitate recovery. Only 160 articles were obtained and, after adding the term "functional outcome," 62 remained for full-text review, of which 21 were eligible. When articles were scored for inclusion of both rehabilitation AND function or functional outcome AND guideline vetting, seven articles remained. One was community based. Nine articles had no recorded vetting process but addressed rehabilitation as an outcome. There is a paucity of CPGs relevant to clinical rehabilitation for burn survivors, likely a result of very few published intervention trials, rare randomized controlled trials addressing rehabilitation, absence of data to establish an evidence base for practice recommendations, an inadequate number of community-based intervention trials, and little patient input. It is likely that rehabilitation of burn survivors will improve if more people gain skills in meeting the needs of people with burn injury. An increase in trained professionals may lead to an increase in intervention trials and research to establish evidence for CPGs. People engaged in burn research have an opportunity to devise a systematic, generally agreed-upon approach toward evaluating burn patients and treatment outcomes that will permit data sharing across the world and assess patients throughout the acute and chronic phases of burn injury. [ABSTRACT FROM AUTHOR]

All judges are concerned about fairness and consistency in sentencing. After United States v. Booker1 rendered the Federal Sentencing Guidelines advisory, I began publishing statements of reasons for each sentence I imposed--to ensure transparency and consistency in my own sentencing. I have reviewed the Article written by my former Law Clerks, Carolin Guentert (2016 to 2017) and Ryan Gerber (2017 to 2018). It is, in general, an accurate portrayal of my sentencing practices, as revealed by the public record, not by personal discussions with these clerks. The Article might prove helpful to other judges and to others involved in the sentencing process. In my opinion, the Article comports with ethical rules.2 To the extent it is required, this Foreword serves as the requisite permission--which I do not think is required--for my former Law Clerks to publish this Article. [ABSTRACT FROM AUTHOR]

Objective: The objective for this manuscript is two-fold: determine the scope of clinical rehabilitation research involving burn-injured persons and assess whether research outcomes include function, return to needed, and desirable routines. Has this research addressed rehabilitation needs of the burn injured?Methods: We performed a scoping review of literature (1990-2016) using the method of Arksey and O'Malley. Search terms included "rehabilitation", "function", "burn injury" and "work". Two independent reviewers identified articles that met criteria for abstract and full review. Variables of interest were counts of the number of intervention studies, studies performed in outpatient settings/inpatient settings, or both; count of the distribution of outcome measures that included impairment, function, participation, return to prior roles and percent of burns rehabilitation publications as a function of total rehabilitation articles published.Results: Sixty-four articles were selected for review and 22 employed an intervention. Nine articles were intervention trials that used functional measures. Of the 22 intervention trials 3 (14%) were performed while subjects were inpatients, 9 (41%) while they were outpatients, and 10 (45%) while they were both. There were 67 articles that met inclusion for work-related studies. Fourteen were intervention trials, 9 utilized functional outcomes and 5 used impairment outcomes exclusively. Less than 1% of clinical rehabilitation research addresses burns injury and <1% of the randomized trials in rehabilitation relates to burn injury CONCLUSIONS: There are few studies, few intervention trials and among these, very few that use function or return to community based activity as outcomes for people with burn injury. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Understanding the impact of disease on function and improving functional outcomes is an important goal of rehabilitation. This scoping review analyzes 25 years of published traumatic brain injury (TBI) clinical rehabilitation research (CRR) to determine the frequency with which function is a research goal. METHODS: The review protocol was prepared by experienced clinical researchers in the field. We used these search terms: "moderate traumatic brain injury" and "severe traumatic brain injury" and "functional outcomes"; and "rehabilitation" and "educational outcomes" or "cognition" or "community roles" or "community integration" "behavior" or "neuropsychology" or "quality of life", or "vocational outcomes" or "work" or "return to work". Publications from January 1, 1990-December 31, 2016 were included. RESULTS: 1,815 articles met initial criteria, of which 202 were intervention studies, 84 were randomized controlled trials and 353 prospective non-intervention studies. The combination of intervention and prospective non-intervention studies (n = 555) were analyzed for the kind of measurement tools used. Impairment measures (60%) and symptom measures (43%) either singly or in combination were most frequently used. Measures of function were employed in fewer than 30%. For single outcomes, 95 publications used impairment measures, 60 used symptoms and only18 used function. There were 117 studies that used neurocognitive measures. Participation/societal integration evaluation tools were used for community integration(n = 77) employment (n = 50) and independent living status (n = 37). DISCUSSION: This scoping review identifies a need for additional types of clinical research in the field of TBI CRR. Much of the research is aimed at mitigating impairment and controlling symptoms rather than promoting function. Future efforts by the CRR community studying TBI should address this need. [ABSTRACT FROM AUTHOR]

This manuscript assesses whether the Veterans Administration Rating System (VADR) correlates with self-reported activities of daily living (ADL) used in the National Survey of Veterans and likelihood of employment. Veterans' disability benefits are determined based on a single-index standardized rating scheme, measured at time of discharge. The primary aim of this study was to assess how this single-index rating of disability for veterans compares to multidimensional measures of disability (ADL and instrumental activities of daily living [IADL]). The relationship between disability ratings and labor market outcomes such as job search behavior and the likelihood of being employed was assessed. Successful labor market reintegration requires both physical/mental well-being, we examined the extent that VADR can capture the relationship between job market behavior and measures of mental/physical health. Kernel regression estimates were obtained of the likelihood of working/looking for work. Mean numbers of IADL and ADL difficulties and medical conditions were positively associated with VADR (p-trend < 0.001). An inverse relationship was observed with VADR and predicted probability of working (p-trend < 0.001). The combination of >4 ADL/IADL deficits and mental health diagnosis increased the likelihood of not working. The probability of not working correlated with VADR when VADR was greater than 40%. [ABSTRACT FROM AUTHOR]

At some point during or after treatment, breast cancer may be considered a chronic illness, presenting many choices for managing the disease, its adverse treatment-related effects, other medical comorbidities as well as the biobehavioral burden of having a life-threatening disease, even for individuals with potentially curable breast cancer. Health care models, such as the chronic care model, the medical home, and the shared care model, provide a context for building survivorship health care models. Goals and characteristics of recently proposed shared care models for cancer survivorship health care delivery closely align with the goals and concepts of the prospective surveillance model (PSM) proposed elsewhere in this supplement to the journal Cancer. Given these similarities, along with the growth and expansion of survivorship care models and impending mandates for delivery, there is merit to considering how implementation of the PSM can be integrated with models of survivorship care delivery. The PSM model will likely face many similar challenges and barriers that have impeded widespread dissemination of other survivorship models of care. There exist opportunities to integrate lessons learned as well as to align efforts to achieve greater impact on the shared goal of improving health outcomes for breast cancer survivors. Cancer 2012;118(8 suppl):. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Cancer-related fatigue (CRF) has been documented as 1 of the most distressing symptoms reported by breast cancer survivors. CRF affects functioning and impacts quality of life. Possible causal factors include physical conditions, affective and cognitive states, proinflammatory cytokines, and metabolic factors. Several common problems are associated with CRF in women with breast cancer, including treatment side effects, obesity, arm/upper quadrant symptoms, sleep disturbances, psychological effects, and comorbid conditions. In this article, the authors review the state of the knowledge regarding these issues and nonpharmacologic and pharmacologic interventions for CRF. Physical activity and psychosocial interventions are recommended for practice. Numerous limitations of past studies need to be considered in the design of future studies. CRF is prevalent in preoperative, postoperative, and ongoing surveillance phases. Throughout the continuum of care for women with breast cancer, clinicians must screen, further assess as indicated, and treat CRF, because it is associated with emotional distress and limits function and willingness to exercise. Cancer 2012;118(8 suppl):. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock (HS) and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs) are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. In this paper, in vitro studies with pulmonary endothelial cells (PECs) reveal that conditioned media (CM) from MSCs and MSC-PEC co-cultures inhibits PEC permeability by preserving adherens junctions (VE-cadherin and &bgr;-catenin). Leukocyte adhesion and adhesion molecule expression (VCAM-1 and ICAM-1) are inhibited in PECs treated with CM from MSC-PEC cocultures. Further support for the modulatory effects of MSCs on pulmonary endothelial function and inflammation is demonstrated in our in vivo studies on HS in the rat. In a rat "fixed volume" model of mild HS, we show that MSCs administered IV potently inhibit systemic levels of inflammatory cytokines and chemokines in the serum of treated animals. In vivo MSCs also inhibit pulmonary endothelial permeability and lung edema with concurrent preservation of the vascular endothelial barrier proteins: VE-cadherin, Claudin-1, and Occludin-1. Leukocyte infiltrates (CD68 and MPO positive cells) are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HSinduced lung injury. [ABSTRACT FROM AUTHOR]

The article discusses the future practice innovation for the field of field of cancer rehabilitation. It highlights considerations for practice innovation models such as evaluation of rehabilitation needs, assessment tools, and new partnerships. It also presents considerations for future education models including as a stand alone subspecialty, medical student training, and residency training.

During synaptic vesicle fusion, the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) protein syntaxin-1 exhibits two conformations that both bind to Munc18-1: a "closed" conformation outside the SNARE complex and an "open" conformation in the SNARE complex. Although SNARE complexes containing open syntaxin-1 and Munc18-1. are essential for exocytosis, the function of closed syntaxin-1 is unknown. We generated knockin/knockout mice that expressed only open syntaxin-1B. Syntaxin-1BOpen mice were viable but succumbed to generalized seizures at 2 to 3 months of age. Binding of Munc18-1 to syntaxin-1 was impaired in syntaxin-1BOpen synapses, and the size of the readily releasable vesicle pool was decreased; however, the rate of synaptic vesicle fusion was dramatically enhanced. Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies. [ABSTRACT FROM AUTHOR]

C2 domains are widespread Ca2+-binding modules. The active zone protein Piccolo (also known as Aczonin) contains an unusual C2A domain that exhibits a low affinity for Ca2+, a Ca2+-induced conformational change and Ca2+-dependent dimerization. We show here that removal of a nine-residue sequence by alternative splicing increases the Ca2+ affinity, abolishes the conformational change and abrogates dimerization of the Piccolo C2A domain. The NMR structure of the Ca2+-free long variant provides a structural basis for these different properties of the two splice forms, showing that the nine-residue sequence forms a ß-strand otherwise occupied by a nonspliced sequence. Consequently, Ca2+-binding to the long Piccolo C2A domain requires a marked rearrangement of secondary structure that cannot occur for the short variant. These results reveal a novel mechanism of action of C2 domains and uncover a structural principle that may underlie the alteration of protein function by short alternatively spliced sequences. [ABSTRACT FROM AUTHOR]

Most C(2)-domains bind to phospholipid bilayers as a function of Ca(2+). Although phospholipid binding is central for the normal functions of C(2)-domain proteins, the precise mechanism of phospholipid binding is unclear. One of the key questions is whether phospholipid binding by C(2)-domains is primarily governed by electrostatic or hydrophobic interactions. We have now examined this question for the C(2)A-domain of synaptotagmin I, a membrane protein of secretory vesicles with an essential function in Ca(2+)-triggered exocytosis. Our results confirm previous data showing that Ca(2+)-dependent phospholipid binding by the synaptotagmin C(2)A-domain is exquisitely sensitive to ionic strength, suggesting an essential role for electrostatic interactions. However, we find that hydrophobic interactions mediated by exposed residues in the Ca(2+)-binding loops of the C(2)A-domain, in particular methionine 173, are also essential for tight phospholipid binding. Furthermore, we demonstrate that the apparent Ca(2+) affinity of the C(2)A-domain is determined not only by electrostatic interactions as shown previously, but also by hydrophobic interactions. Together these data indicate that phospholipid binding by the C(2)A-domain, although triggered by an electrostatic Ca(2+)-dependent switch, is stabilized by a hydrophobic mechanism. As a result, Ca(2+)-dependent phospholipid binding proceeds by a multimodal mechanism that mirrors the amphipathic nature of the phospholipid bilayer. The complex phospholipid binding mode of synaptotagmins may be important for its role in regulated exocytosis of secretory granules and synaptic vesicles. [ABSTRACT FROM AUTHOR]

Most C[sub 2]-domains bind to phospholipid bilayers as a function of Ca[sup 2+]. Although phospholipid binding is central for the normal functions of C[sub 2]-domain proteins, the precise mechanism of phospholipid binding is unclear. One of the key questions is whether phospholipid binding by C[sub 2]-domains is primarily governed by electrostatic or hydrophobic interactions. We have now examined this question for the C[sub 2]A-domain of synaptotagmin I, a membrane protein of secretory vesicles with an essential function in Ca[sup 2+]-triggered exocytosis. Our results confirm previous data showing that Ca[sup 2+]-dependent phospholipid binding by the synaptotagmin C[sub 2]A-domain is exquisitely sensitive to ionic strength, suggesting an essential role for electrostatic interactions. However, we find that hydrophobic interactions mediated by exposed residues in the Ca[sup 2+]-binding loops of the C[sub 2]A-domain, in particular methionine 173, are also essential for tight phospholipid binding. Furthermore, we demonstrate that the apparent Ca[sup 2+] affinity of the C[sub 2]A-domain is determined not only by electrostatic interactions as shown previously, but also by hydrophobic interactions. Together these data indicate that phospholipid binding by the C[sub 2]A-domain, although triggered by an electrostatic Ca[sup 2+]-independent switch, is stabilized by a hydrophobic mechanism. As a result, Ca[sup 2+]-dependent phospholipid binding proceeds by a multimodal mechanism that mirrors the amphipathic nature of the phospholipid bilayer. The complex phospholipid binding mode of synaptotagmins may be important for its role in regulated exocytosis of secretory granules and synaptic vesicles. Diabetes 51 (Suppl. 1):S12–S18, 2002 [ABSTRACT FROM AUTHOR]

Regulated exocytosis forms the basis for many intercellular signaling processes, for example, in hormone secretion or neurotransmitter release. During regulated exocytosis, the membrane of a secretory vesicle fuses with the plasma membrane in a tightly controlled reaction that is most often triggered by calcium. Recent advances have allowed major insights into the molecular mechanisms that mediate regulated exocytosis. In the present review, we will briefly discuss two key features of regulated exocytosis that have been particularly well studied recently. First, we will examine the current understanding of the membrane fusion reaction that underlies regulated exocytosis and that is effected by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) and munc18-like proteins similar to other membrane fusion reactions. Second, we will describe the role of the major candidates for the calcium sensors that trigger exocytosis, a protein family called synaptotagmins. Although our understanding of regulated exocytosis is as yet incomplete, the results from the studies of SNAREs, munc18s, and synaptotagmins have provided a molecular anchor for a more complete future description. [ABSTRACT FROM AUTHOR]

Ca2+ regulation of neurotransmitter release is thought to require multiple Ca2+ sensors with distinct affinities. However, no low‐affinity Ca2+ sensor has been identified at the synapse. We now show that piccolo/aczonin, a recently described active‐zone protein with C‐terminal C2A‐ and C2B‐domains, constitutes a presynaptic low‐affinity Ca2+ sensor. Ca2+ binds to piccolo by virtue of its C2A‐domain via an unusual mechanism that involves a large conformational change. The distinct Ca2+‐binding properties of the piccolo C2A‐ domain are mediated by an evolutionarily conserved sequence at the bottom of the C2A‐domain, which may fold back towards the Ca2+‐binding sites on the top. Point mutations in this bottom sequence inactivate it, transforming low‐affinity Ca2+ binding (100–200 μM in the presence of phospholipids) into high‐affinity Ca2+ binding (12–14 μM). The unusual Ca2+‐binding mode of the piccolo C2A‐domain reveals that C2‐domains are mechanistically more versatile than previously envisaged. The low Ca2+ affinity of the piccolo C2A‐domain suggests that piccolo could function in short‐term synaptic plasticity when Ca2+ concentrations accumulate during repetitive stimulation. [ABSTRACT FROM AUTHOR]

Ca2+ regulation of neurotransmitter release is thought to require multiple Ca2+ sensors with distinct affinities. However, no low-affinity Ca2+ sensor has been identified at the synapse. We now show that piccolo/ aczonin, a recently described active-zone protein with C-terminal C2A- and C2B-domains, constitutes a pre- synaptic tow-affinity Ca2+ sensor. Ca2+ binds to piccolo by virtue of its C2A-domain via an unusual mechanism that involves a large conformational change. The distinct Ca2+-binding properties of the piccolo C2A- domain are mediated by an evolutionarily conserved sequence at the bottom of the CA-domain, which may fold back towards the Ca2+-binding sites on the top. Point mutations in this bottom sequence inactivate it, transforming tow-affinity Ca2+ binding (100-200 μM in the presence of phospholipids) into high-affinity Ca2+ binding (12-14 μM). The unusual Ca2+-binding mode of the piccolo C2A-domain reveals that C2-domains are mechanistically more versatile than previously envisaged. The tow Ca2+ affinity of the piccolo C2A-domain suggests that piccolo could function in short-term synaptic plasticity when Ca2+ concentrations accumulate during repetitive stimulation. [ABSTRACT FROM AUTHOR]

Investigates the role of transient changes in intracellular free sodium concentration ([Na+]i) and intracellular free calcium concentration ([Ca 2+]i) in nicotine-evoked norepinephrine release from bovine adrenal chromaffin cells. Sodium-binding benzofuran isophtalate (SBFI) as fluorescence indicator; Nicotine-induced release of catecholamines.

Background: Endoscopic ultrasound-guided fine-needle aspiration fails to diagnose up to 25% of patients with pancreatic ductal adenocarcinoma (PDAC). Proteomics can help to overcome this clinical dilemma. We hypothesized that soluble protein signatures can differentiate PDAC from benign tissues.Study Design: Tissues were obtained from resected surgical specimens, lysed, and homogenates collected for analysis with a 41-protein multiplex assay. Analyte concentrations were normalized to total protein. Statistical analysis was performed to evaluate for differences in PDAC vs benign tissue.Results: Tissues were obtained from 159 patients, 82 patients with PDAC naïve to therapy and 77 with benign pancreatic pathology. Fourteen analytes had a receiver operating characteristic curve area of >0.75 for predicting PDAC vs benign tissue. A recursive partitioning model using only 2 analytes, interleukin 1 receptor antagonist and transforming growth factor-α, provided an accuracy, sensitivity, and specificity of 91.2%, 90.2%, and 92.2%, respectively. A penalized logistic regression model found 12 analytes that provide diagnostic value to a protein signature. The mean area under the receiver operating characteristic after 50 tenfold cross-validations was 0.951. Accuracy, sensitivity, and specificity of this model were 91.2%, 87.8%, and 94.8%, respectively. Applying the scenario of 80% disease prevalence in patients undergoing endoscopic ultrasound with fine-needle aspiration for a pancreatic head mass, positive predictive value is 98.5% (95% CI 93.0% to 99.7%) and negative predictive value is 66.0% (95% CI 54.9% to 75.6%).Conclusions: Protein signatures from pancreatic specimens can differentiate PDAC from benign tissue. Additional work to validate these findings in a unique sample set is warranted. [ABSTRACT FROM AUTHOR]

While much is known about the quality of social behavior among neurotypical individuals and those with autism spectrum disorder (ASD), little work has evaluated quantity of social interactions. This study used ecological momentary assessment (EMA) to quantify in vivo daily patterns of social interaction in adults as a function of demographic and clinical factors. Adults with and without ASD (N ASD = 23, N Neurotypical = 52) were trained in an EMA protocol to report their social interactions via smartphone over one week. Participants completed measures of IQ, ASD symptom severity and alexithymia symptom severity. Cyclical multilevel models were used to account for nesting of observations. Results suggest a daily cyclical pattern of social interaction that was robust to ASD and alexithymia symptoms. Adults with ASD did not have fewer social interactions than neurotypical peers; however, severity of alexithymia symptoms predicted fewer social interactions regardless of ASD status. These findings suggest that alexithymia, not ASD severity, may drive social isolation and highlight the need to reevaluate previously accepted notions regarding differences in social behavior utilizing modern methods. • Compared to adults without autism, those with autism demonstrated a similar amount and pattern of social interactions. • Difficulties with identifying emotions in both the self and others were associated with fewer social interactions. • Therapy for adults with autism may more appropriately focus on improving quality – not quantity – of social interactions. • Identifying these symptoms may improve detection of those experiencing social difficulties, regardless of autism status. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a debilitating condition seen frequently in patients with pancreatic ductal adenocarcinoma (PDAC). The underlying mechanisms driving cancer cachexia are not fully understood but are related, at least in part, to the immune response to the tumor both locally and systemically. We hypothesize that there are unique differences in cytokine levels in the tumor microenvironment and systemic circulation between PDAC tumors and that these varying profiles affect the degree of cancer cachexia observed. Patient demographics, operative factors, oncologic factors, and perioperative data were collected for the two patients in the patient derived xenograft (PDX) model. Human pancreatic cancer PDX were created by implanting fresh surgical pancreatic cancer tissues directly into immunodeficient mice. At PDX end point, mouse tumor, spleen and muscle tissues were collected and weighed, muscle atrophy related gene expression measured, and tumor and splenic soluble proteins were analyzed. PDX models were created from surgically resected patients who presented with different degrees of cachexia. Tumor free body weight and triceps surae weight differed significantly between the PDX models and control (P < 0.05). Both PDX groups had increased atrophy related gene expression in muscle compared to control (FoxO1, Socs3, STAT3, Acvr2b, Atrogin-1, MuRF1; P < 0.05). Significant differences were noted in splenic soluble protein concentrations in 14 of 15 detected proteins in tumor bearing mice when compared to controls. Eight splenic soluble proteins were significantly different between PDX groups (P < 0.05). Tumor soluble proteins were significantly different between the two PDX groups in 15 of 24 detected proteins (P < 0.05). PDX models preserve the cachectic heterogeneity found in patients and are associated with unique cytokine profiles in both the spleen and tumor between different PDX. These data support the use of PDX as a strategy to study soluble cachexia protein markers and also further efforts to elucidate which cytokines are most related to cachexia in order to provide potential targets for immunotherapy. [ABSTRACT FROM AUTHOR]

When autistic youth are asked to assess their own social skills, they frequently rate themselves more favorably than their parents rate them. The magnitude of this informant discrepancy has been shown to relate to key clinical outcomes such as treatment response. It has been proposed that this discrepancy arises from difficulties with Theory of Mind. Participants were 167 youth 11 to 17 years old; 72% male, and their parents. Youth completed self-report measures of social skills and social cognitive tasks, while their parents completed questionnaires regarding social skills. A repeated-measures ANOVA indicated both non-autistic and autistic youth rated themselves more favorably than their parents rated them across all measures. Zero-order correlations revealed that raw differences between parent- and participant-report were negatively correlated with scores on parent-reported Theory of Mind measures. However, polynomial analysis did not indicate interaction effects between parent- and participant-report on any of the measures used. Polynomial regression revealed that increases in parent-reported social skill predicted larger increases in parent-report Theory of Mind at low levels of parent-reported social skill compared to high levels of parent-reported social skill. Participant-report social skills predicted performance on a behavioral Theory of Mind test in a curvilinear fashion, such that the relationship was positive at low levels of participant-reported social skills, but negative at high levels. This study replicates the finding that raw difference score analyses may result in illusory effects that are not supported when using more contemporary analysis methods, and that more complex and subtle relationships between social insight and perspective-taking exist within autistic youth. [ABSTRACT FROM AUTHOR]

Reports on the frequency of joint laxity, scoliosis and thoracic cage asymmetry in children with Beckwith-Wiedemann syndrome (BWS). Description of BWS; Assessment of possible associations between musculoskeletal abnormalities and cancer frequency in children with BWS.

Atypical social communication is a key indicator of autism spectrum disorder and has long been presumed to interfere with friendship formation and first impressions among typically developing youth. However, emerging literature suggests that such atypicalities may function differently among groups of peers with autism spectrum disorder. The current study aimed to investigate the relationship between atypical social communication patterns and first impression sociometric ratings by peers in groups of youth with autism spectrum disorder. Findings suggest that, contrary to typically developing individuals, several forms of atypical communication among youth with autism spectrum disorder are associated with more positive first impressions by others with autism spectrum disorder. This suggests that interventions designed to increase friendships among youth with autism spectrum disorder may benefit from reframing their approach to addressing atypical social communication. Individuals with autism spectrum disorder demonstrate differences in aspects of social communication, including tone of voice, use of gestures, eye contact, and facial expressions. These social communication differences in autism spectrum disorder can negatively impact friendship formation with peers without autism spectrum disorder. However, little is known about how these differences in social behaviors impact friendship formations between peers with autism spectrum disorder. Moreover, recent research suggests that these very differences may facilitate more effective communication among peers with autism spectrum disorder. Thus, we aimed to investigate the relationship between these differences in social communication and first impressions of peers with autism spectrum disorder, looking specifically at how much peers liked/disliked each other, whether they felt they had become friends, and whether they wanted to play together again. We found that differences in social communication (particularly, eye contact and facial expressions) led to better first impressions as rated by peers with autism spectrum disorder. These results suggest that differences in social communication may not simply be a deficit for youth; rather they may actually help build friendships among peers with autism spectrum disorder. This is important because current social skills interventions generally aim to reduce social communication differences, which may have negative consequences for friendships between peers with autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Background: Myofascial Pain Syndrome (MPS) is a common pain disorder. Diagnostic criteria include physical findings which are often unreliable or not universally accepted. A precise biosignature may improve diagnosis and treatment effectiveness. The purpose of this study was to assess whether microanalytic assays significantly correlate with characteristic clinical findings in people with MPS. Methods: This descriptive, prospective study included 38 participants (25 women) with greater than 3 months of myofascial pain in the upper trapezius. Assessments were performed at a university laboratory. The main outcome measures were the Beighton Index, shoulder range of motion, strength asymmetries and microanalytes: DHEA, Kynurenine, VEGF, interleukins (IL-1b, IL-2, IL-4, IL-5, IL-7, IL-8, IL-13), growth factors (IGF-1, IGF2, G-CSF, GM-CSF), MCP-1, MIP-1b, BDNF, Dopamine, Noradrenaline, NPY, and Acetylcholine. Mann–Whitney test and Spearman's multivariate correlation were applied for all variables. The Spearman's analysis results were used to generate a standard correlation matrix and heat map matrix. Results: Mean age of participants was 32 years (20–61). Eight (21%) had widespread pain (Widespread Pain Index ≥ 7). Thirteen (34%) had MPS for 1–3 years, 14 (37%) 3–10 years, and 11 (29%) for > 10 years. The following showed strong correlations: IL1b,2,4,5,7,8; GM-CSF and IL 2,4,5,7; between DHEA and BDNF and between BDNF and Kynurenine, NPY and acetylcholine. The heat map analysis demonstrated strong correlations between the Beighton Index and IL 5,7, GM-CSF, DHEA. Asymmetries of shoulder and cervical spine motion and strength associated with select microanalytes. Conclusion: Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to identify the impact of postacute SARS-CoV-2 infection on patient outcomes. Design: This is a prospective, repeated measure, observational study of consented adults with positive SARS-CoV-2 quantitative polymerase chain reaction or antigen test more than 28 days after infection. Only data from the initial study visit are reported, including disease history, symptoms checklist, patient questionnaires, cognitive tests, social/medical histories, vitals, grip strength, and 2-min walk distance. Results: Two hundred eighteen patients were studied: 100 hospitalized (57.3 ± 15.4 yrs, 62% male, body mass index: 31.3 ± 8.0) and 118 nonhospitalized (46.2 ± 14.6 yrs, 31% male, body mass index: 29.7 ± 7.5). Post-COVID patients reported mean 1.76 symptoms; ≥15% reported fatigue, memory loss, and shortness of breath. Grip strength was 14% lower than norms (P < 0.0001). Fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue), mood (Patient Health Questionnaire), and well-being (EuroQol 5 Dimension 5 Level) scores were lower than the population norms (P < 0.05). Hospitalized versus nonhospitalized post-COVID patients performed worse on cognitive assessments (processing speed test—Wechsler Adult Intelligence Scale–Fourth Edition Symbol Search) and reported less regular exercise (≥30 mins ≥3× per week; P < 0.05). In addition, 30% had severe fatigue (by the Functional Assessment of Chronic Illness Therapy–Fatigue); those patients reported less exercise (P < 0.05). In multivariate models, lack of exercise was independently associated with multiple post–COVID-19 impairments. Conclusions: Low levels of exercise are an independent risk factor for post-COVID sequelae. Patients who report less exercise have low grip strength, higher levels of fatigue, memory loss, shortness of breath, depression, and poorer quality of life. [ABSTRACT FROM AUTHOR]

In pancreatic cancer clinical trials, Black patients are under-represented while having higher morbidity and mortality rates as compared to other racial groups. Multiple factors, including socioeconomic and lifestyle factors may contribute to this disparity, but genomic contributions remain unclear. In an exploratory project to identify genes that may contribute to differences in survival between Black (n = 8) and White (n = 20) patients with pancreatic cancer, transcriptomic sequencing of over 24,900 genes was performed in human pancreatic tumor and non-tumor tissue obtained from Black and White patients. Over 4,400 genes were differentially expressed in tumor and non-tumor tissue, irrespective of race. To validate these results, the expression of four genes (AGR2, POSTN, TFF1, and CP) reported to be up-regulated in pancreatic tumor tissue as compared to non-tumor tissue were confirmed using quantitative PCR. Transcriptomic analysis that compared pancreatic tumor tissue from Black and White patients revealed differential expression in 1,200 genes, while a comparison of the non-tumor and tumor gene expression differences within each race revealed over 1,500 tumor-specific differentially expressed genes in pancreatic tumor and non-tumor tissue from Black patients. We identified TSPAN8 as a potential tumor-specific gene significantly overexpressed in pancreatic tumor tissue in Black patients as compared to White patients. Using Ingenuity Pathway Analysis software to compare the race-associated gene expression profiles, over 40 canonical pathways were identified to be potentially impacted by the gene expression differences between the races. Heightened expression of TSPAN8 was associated with poor overall survival, suggesting TSPAN8 as one potential genetic factor contributing to the differential outcomes in Black patients with pancreatic cancer, supporting the potential utility of larger genomic studies to further explore the role of TSPAN8 in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Measuring function with valid and responsive tools in patients with cancer is essential for driving clinical decision‐making and for the end points of clinical trials. Current patient‐reported outcome measurements of function fall short for many reasons. This study evaluates the responsiveness of the Patient‐Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile, a novel measure of function across multiple domains. Methods: Two hundred nine participants across five geographically distinct tertiary care centers completed the assessment and pain rating at two outpatient cancer rehabilitation clinic visits. Patients and providers completed a global rating of change measure at the second visit to indicate whether the patient was improving or worsening in function. Multiple response indices and linear models measured whether the measure was responsive to self‐reported and clinician‐rated changes over time. Correlations between changes in function and changes in anchors (pain rating and performance status) were also calculated. Results: Function as measured by the PROMIS Cancer Function Brief 3D Profile changed appropriately as both patients and clinicians rated change. Small to moderate effect sizes supported the tool's responsiveness. Function was moderately correlated with pain and more strongly correlated with performance status, and changes in function corresponded with changes in anchor variables. No floor/ceiling effect was found. Conclusions: The PROMIS Cancer Function Brief 3D Profile is sensitive to changes over time in patients with cancer. The measure may be useful in clinical practice and as an end point in clinical trials. Lay summary: We gave patients a questionnaire by which they told their physicians how well they were functioning, including how fatigued they were.This study tested that questionnaire to see whether the scores would change if patients got better or worse. Lay summary: We gave patients a questionnaire by which they told their physicians how well they were functioning, including how fatigued they were.This study tested that questionnaire to see whether the scores would change if patients got better or worse. Short Abstract The PROMIS Cancer Function Brief 3D Profile was found to be responsive to measuring change in function in patients with cancer. The changes were correlated with changes in performance status, pain, and both patient‐ and physician‐reported global ratings of change. [ABSTRACT FROM AUTHOR]

The "relevance" of research to stakeholders is an important factor in influencing the uptake of new knowledge into practice; however, this concept is neither well defined nor routinely incorporated in clinical rehabilitation research. Developing a uniform definition, measurement standards, stakeholder engagement strategies, and guiding frameworks that bolster relevance may help incorporate the concept as a key element in research planning and design. This article presents a conceptual argument for why relevance matters, proposes a working definition, and suggests strategies for operationalizing the construct in the context of clinical rehabilitation research. We place special emphasis on the importance of promoting relevance to patients, caregivers, and clinicians and provide preliminary frameworks and innovative study designs that can assist clinical rehabilitation researchers in doing so. We argue that researchers who include a direct statement regarding why and to whom a study is relevant and who incorporate considerations of relevance throughout all phases of study design produce more useful research for patients, caregivers, and clinicians, increasing its chance of uptake into practice. Consistent consideration of relevance, particularly to nonacademic audiences, during the conceptualization, study design, presentation, and dissemination of clinical rehabilitation research may promote the uptake of findings by patients, caregivers, and providers. [ABSTRACT FROM AUTHOR]

Background Neutralizing monoclonal antibody (NmAb) treatments have received Emergency Use Authorization to treat patients with mild or moderate COVID-19 infection. To date, no real- world data on the efficacy of NmAbs have been reported from clinical practice. We assessed the impact of NmAb treatment given in the outpatient clinical practice setting on hospital utilization. Methods Electronic medical records were used to identify adult COVID-19 patients who received NmAbs (bamlanivimab [BAM] or casirivimab and imdevimab [REGN-COV2]) and historic COVID-19 controls. Post-index hospitalization rates were compared. Results 707 confirmed COVID-19 patients received NmAbs and 1709 historic COVID-19 controls were included; 553 (78%) received BAM, 154 (22%) received REGN-COV2. Patients receiving NmAb infusion had significantly lower hospitalization rates (5.8% vs 11.4%, P  < .0001), shorter length of stay if hospitalized (mean, 5.2 vs 7.4 days; P  = .02), and fewer ED visits within 30 days post-index (8.1% vs 12.3%, P  = .003) than controls. Hospitalization-free survival was significantly longer in NmAb patients compared with controls (P  < .0001). There was a trend towards a lower hospitalization rate among patients who received NmAbs within 2–4 days after symptom onset. In multivariate analysis, having received an NmAb transfusion was independently associated with a lower risk of hospitalization after adjustment for age, sex, race, BMI, and referral source (adjusted HR [95% CI],.54 [0.38–0.79]; P  = .0012). Overall mortality was not different between the 2 groups. Conclusions NmAb treatment reduced hospital utilization, especially when received within a few days of symptom onset. Further study is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Current blood banking practices allow fresh frozen plasma (FFP) to be thawed and then stored for 5 d between 1 and 6 °C. We hypothesized that aged plasma (d 5 FFP) would be pro-inflammatory to the endothelium compared with fresh plasma (d 0 FFP). Materials and Methods: Human pulmonary endothelial cells (PECs) were treated with (1) media, (2) media + lipopolysaccharide (LPS), (3) lactated Ringer''s (LR), (4) LR + LPS, (5) d 0 FFP, (6) d 0 FFP + LPS, (7) d 5 FFP, and (8) d 5 FFP + LPS. After a 24 h incubation, the PECs were stained with antibodies for I-CAM, V-CAM, P-selectin, and E-selectin. The cells were subsequently analyzed by flow cytometry. Results: In both PEC groups treated with FFP and stimulated with LPS, I-CAM, V-CAM, P-selectin, and E-selectin were significantly up-regulated compared with LR when stimulated by LPS. Conclusion: FFP at both ages significantly increased expression of four different adhesion molecules compared with LR in PECs. This may represent a possible mechanism for increased leukocyte binding on the endothelium as a result of FFP transfusion. [Copyright &y& Elsevier]

Piccolo and bassoon are highly homologous multidomain proteins of the presynaptic cytomatrix whose function is unclear. Here, we generated piccolo knockin/knockout mice that either contain wildtype levels of mutant piccolo unable to bind Ca2+ (knockin), ∼6O% decreased levels of piccolo that is C-terminally truncated (partial knockout), or <5% levels of piccolo (knockout). All piccolo mutant mice were viable and fertile, but piccolo knockout mice exhibited increased postnatal mortality. Unexpectedly, electrophysiology and electron microscopy of piccolo-deficient synapses failed to uncover a major phenotype either in acute hippocampal slices or in cultured cortical neurons. To unmask potentially redundant functions of piccolo and bassoon, we thus acutely knocked down expression of bassoon in wild-type and piccolo knockout neurons. Despite a nearly complete loss of piccolo and bassoon, however, we still did not detect an electrophysiological phenotype in cultured piccoloand bassoondeficient neurons in either GABAergic or glutamatergic synaptic transmission. In contrast, electron microscopy revealed a significant reduction in synaptic vesicle clustering in double bassoon/piccolodeficient synapses. Thus, we propose that piccolo and bassoon play a redundant role in synaptic vesicle clustering in nerve terminals without directly participating in neurotransmitter release. [ABSTRACT FROM AUTHOR]

Background: Given the rapid spread of COVID-19 and its associated morbidity and mortality, healthcare providers throughout the world have been forced to constantly update and change their care delivery models. Objective: To assess the outcomes of COVID-19 hospitalized patients during the course of the pandemic in a well-integrated health system. Methods: The study used data from the electronic health medical records to assess trends in clinical profile and outcomes of hospitalized adult COVID-19 patients hospitalized in our 5-hospital health system from March 2020-May 2021 (n = 6865). Integration of the health system began in February 2020 and was fully actualized by March 30, 2020. Results: Mortality decreased from 15% during first peak (March-May 2020; the rate includes 19% in March-April and 10% in May 2020) to 6% in summer-fall 2020, increased to 13% during the second peak (November 2020-January 2021), and dropped to 7% during the decline period (February-May 2021) (p<0.01). Resource utilization followed a similar pattern including a decrease in ICU use from 35% (first peak) to 16% (decline period), mechanical ventilation from 16% (first peak, including 45% in March 2020) to 9–11% in subsequent periods (p<0.01). Independent predictors of inpatient mortality across multiple study periods included older age, male sex, higher multi-morbidity scores, morbid obesity, and indicators of severe illness on admission such as oxygen saturation ≤90% and high qSOFA score (all p<0.05). However, admission during the first peak remained independently associated with increased mortality even after adjustment for patient-related factors: odds ratio = 1.8 (1.4–2.4) (p<0.0001). Conclusions: The creation of a fully integrated health system allowed us to dynamically respond to the everchanging COVID-19 landscape. In this context, despite the increasing patient acuity, our mortality and resource utilization rates have improved during the pandemic. [ABSTRACT FROM AUTHOR]

Studies a point mutation in Ca[sup2+]-binding protein synaptotagmin I that causes a twofold decrease in overall Ca[sup2+] affinity without inducing structural or conformational changes. How the introduction by homologous recombination into the endogenous synaptotagmin I gene in mice decreases the Ca[sup2+] sensitivity of neurotransmitter release twofold, but does not alter spontaneous release of the size of the readily releasable pool of neurotransmitters; Conclusion.

Purpose: The number of cancer survivors worldwide is growing, with over 15.5 million cancer survivors in the United States alone—a figure expected to double in the coming decades. Cancer survivors face unique health challenges as a result of their cancer diagnosis and the impact of treatments on their physical and mental well-being. For example, cancer survivors often experience declines in physical functioning and quality of life while facing an increased risk of cancer recurrence and all-cause mortality compared with persons without cancer. The 2010 American College of Sports Medicine Roundtable was among the first reports to conclude that cancer survivors could safely engage in enough exercise training to improve physical fitness and restore physical functioning, enhance quality of life, and mitigate cancer-related fatigue. Methods: A second Roundtable was convened in 2018 to advance exercise recommendations beyond public health guidelines and toward prescriptive programs specific to cancer type, treatments, and/or outcomes. Results: Overall findings retained the conclusions that exercise training and testing were generally safe for cancer survivors and that every survivor should "avoid inactivity." Enough evidence was available to conclude that specific doses of aerobic, combined aerobic plus resistance training, and/or resistance training could improve common cancer-related health outcomes, including anxiety, depressive symptoms, fatigue, physical functioning, and health-related quality of life. Implications for other outcomes, such as peripheral neuropathy and cognitive functioning, remain uncertain. Conclusions: The proposed recommendations should serve as a guide for the fitness and health care professional working with cancer survivors. More research is needed to fill remaining gaps in knowledge to better serve cancer survivors, as well as fitness and health care professionals, to improve clinical practice. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Introduction: The American College of Sports Medicine convened an International Multidisciplinary Roundtable on Exercise and Cancer in March 2018 to evaluate and translate the evidence linking physical activity and cancer prevention, treatment, and control. This article discusses findings from the Roundtable in relation to the biologic and epidemiologic evidence for the role of physical activity in cancer prevention and survival. Results: The evidence supports that there are a number of biologically plausible mechanisms, whereby physical activity can influence cancer risk, and that physical activity is beneficial for the prevention of several types of cancer including breast, colon, endometrial, kidney, bladder, esophageal, and stomach. Minimizing time spent in sedentary behavior may also lower risk of endometrial, colon and lung cancers. Conversely, physical activity is associated with higher risk of melanoma, a serious form of skin cancer. Further, physical activity before and after a cancer diagnosis is also likely to be relevant for improved survival for those diagnosed with breast and colon cancer; with data suggesting that postdiagnosis physical activity provides greater mortality benefits than prediagnosis physical activity. Conclusions: Collectively, there is consistent, compelling evidence that physical activity plays a role in preventing many types of cancer and for improving longevity among cancer survivors, although the evidence related to higher risk of melanoma demonstrates the importance of sun safe practices while being physically active. Together, these findings underscore the importance of physical activity in cancer prevention and control. Fitness and public health professionals and health care providers worldwide are encouraged to spread the message to the general population and cancer survivors to be physically active as their age, abilities, and cancer status will allow. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine if laparoscopic pancreatoduodenectomy (LPD) is a cost-effective alternative to open pancreatoduodenectomy (OPD).Methods: Hospital cost data, discharge disposition, readmission rates, and readmission costs from periampullary cancer patient cohorts of LPD and OPD were compared. The surgical cohorts over a 40-month period were clinically similar, consisting of 52 and 50 patients in the LPD and OPD groups, respectively.Results: The total operating room costs were higher in the LPD group as compared to the OPD group (median US$12,290 vs US$11,299; P = 0.05) due to increased costs for laparoscopic equipment and regional nerve blocks (P ≤ 0.0001). Although hospital length of stay was shorter in the LPD group (median 7 vs 8 days; P = 0.025), the average hospital cost was not significantly decreased compared to the OPD group (median $28,496 vs $28,623). Surgery-related readmission rates and associated costs did not differ between groups. Compared to OPD patients, significantly more LPD patients were discharged directly home rather than to other healthcare facilities (88% vs 72%; P = 0.047).Conclusion: For the index hospitalization, the cost of LPD is equivalent to OPD. Total episode-of-care costs may favor LPD via reduced post-hospital needs for skilled nursing and rehabilitation. [ABSTRACT FROM AUTHOR]

Background Discrepancy between informants (parents and teachers) in severity ratings of core symptoms commonly arise when assessing autism spectrum disorder ( ASD). Whether such discrepancy yields unique information about the ASD phenotype and its clinical correlates has not been examined. We examined whether degree of discrepancy between parent and teacher ASD symptom ratings defines discrete, clinically meaningful subgroups of youth with ASD using an efficient, cost-effective procedure. Methods Children with ASD ( N = 283; 82% boys; Mage = 10.5 years) were drawn from a specialty ASD clinic. Parents and teachers provided ratings of the three core DSM- IV- TR domains of ASD symptoms (communication, social, and perseverative behavior) with the Child and Adolescent Symptom Inventory-4R ( CASI-4R). External validators included child psychotropic medication status, frequency of ASD-relevant school-based services, and the Autism Diagnostic Observation Schedule ( ADOS-2). Results Four distinct subgroups emerged that ranged from large between-informant discrepancy (informant-specific) to relative lack of discrepancy (i.e. informant agreement; cross-situational): Moderate Parent/Low Teacher or Low Parent/Moderate Teacher Severity (Discrepancy), and Moderate or High Symptom Severity (Agreement). Subgroups were highly distinct (mean probability of group assignment = 94%). Relative to Discrepancy subgroups, Agreement subgroups were more likely to receive psychotropic medication, school-based special education services, and an ADOS-2 diagnosis. These differential associations would not have been identified based solely on CASI-4R scores from one informant. Conclusions The degree of parent-teacher discrepancy about ASD symptom severity appears to provide more clinically useful information than reliance on a specific symptom domain or informant, and thus yields an innovative, cost-effective approach to assessing functional impairment. This conclusion stands in contrast to existing symptom clustering approaches in ASD, which treat within-informant patterns of symptom severity as generalizable across settings. Within-child variability in symptom expression across settings may yield uniquely useful information for characterizing the ASD phenotype. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this investigation was to determine if it was possible to separate fatigue self-reports into two distinct types of fatigue symptom clusters in research subjects with chronic liver disease (CLD). It was hypothesized that when items from the Medical Outcomes Study Short-Form (SF-36v2) are combined with items from the Fatigue Severity Scale (FSS), these distinct factors will emerge.Methods: Confirmatory and exploratory factor analyses from data collected in a prospective, natural history study of CLD patients were conducted. Items were selected from the SF-36v2 and the FSS for entry into the factor analyses. In order to establish convergent and discriminant validity, derived factor scores were correlated with subscale scores of the Human Activity Profile (HAP), Mental Component Score (MCS) from the SF-36v2, and the Emotional Functioning Subscale of the Chronic Liver Disease Questionnaire (CLDQ-EF).Results: 106 participants with CLD were included (50% female; age: 51 ± 10). Two factors were identified. The factors included one that clustered around questions addressing fatigue related to physical activity (peripheral fatigue) and the other to the questions addressing generalized fatigue that did not require physical tasks to produce the fatigue (central fatigue). The standardized factor loadings of all items were greater than 0.6 on their underlying constructs. Moreover, all factor loadings are significant at p < 0.01. Peripheral fatigue was related to HAP (r = 0.26, r = 0.24, p < 0.01), as was central fatigue (r = -0.34, r = -0.33, p < 0.01). Central fatigue was related to MCS and CLDQ-EF (r = -0.60; r = -0.63, p < 0.01), whereas peripheral fatigue was not (r = 0.07, p > 0.40). We then tested the original scales to determine if the newly created factors correlated better with the validity measures. The full FSS did not correlate as well as the newly created central fatigue scale, while the original peripheral fatigue scale (the SF-36v2 physical functioning) was more related to HAP than the newly created scale.Conclusions: In individuals with CLD, two separate factors pertaining to fatigue were identified. This recognition of the multifaceted nature of fatigue may help increase the specificity of self-reports of fatigue and lead to treatments that can specifically address the underlying factors contributing to fatigue. [ABSTRACT FROM AUTHOR]

Background: People want to live independently, but too often disabilities or advanced age robs them of the ability to do the necessary activities of daily living (ADLs). Finding relationships between electromyograms measured in the arm and movements of the hand and wrist needed to perform ADLs can help address performance deficits and be exploited in designing myoelectrical control systems for prosthetics and computer interfaces.Methods: This paper reports on several machine learning techniques employed to discover the electromyogram patterns present when performing 24 typical fine motor functional activities of the hand and the rest position used to accomplish ADLs. Accelerometer data is collected from the hand as an aid in identifying the start and end of movements and to help in labeling the signal data. Techniques employed include classification of 100 ms individual signal instances, using a symbolic representation to approximate signal streams, and the use of nearest neighbor in two specific situations: creation of an affinity matrix to model learning instances and classify based on multiple adjacent signal values, and using Dynamic Time Warping (DTW) as a distance measure to classify entire activity segments.Results: Results show the patterns can be learned to an accuracy of 76.64 % for a 25 class problem when classifying 100 ms instances, 83.63 % with the affinity matrix approach with symbolic representation, and 85.22 % with Dynamic Time Warping. Classification errors are, with a few exceptions, concentrated within particular grip action groups.Conclusion: The findings reported here support the view that grips and movements of the hand can be distinguished by combining electrical and mechanical properties of the task to an accuracy of 85.22 % for a 25 class problem. Converting the signals to a symbolic representation and classifying based on larger portions of the signal stream improve classification accuracy. This is both clinically useful and opens the way for an approach to help simulate hand functional activities. With improvements it may also prove useful in real time control applications. [ABSTRACT FROM AUTHOR]