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Limited access to health care services and the self-isolation measures due to the coronavirus disease 2019 (COVID-19) pandemic may have had additional unintended negative effects, affecting the health of individuals with spinal cord injury (SCI).To examine the perceived influence of the COVID-19 pandemic on individuals with SCI. First, this study looked to understand how the pandemic affected the use and perception of telehealth services for these individuals. Second, it investigated the effect of COVID-19 on mental health.Cross-sectional online survey.Individuals with SCI living in the community in British Columbia, Canada.This survey was offered to individuals with SCI and had 71 respondents, with 34% living in a rural setting and 66% in an urban setting.Not applicable.Telehealth utility, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), Fear of COVID-19 scale (FCV-19S), and Perceived Vulnerability to Disease (PVD).Telehealth use in the SCI population has increased from 9.9% to 25.4% over the pandemic, with rates of telehealth use in urban centers nearing those of rural participants. Thirty-one percent of respondents had probable depression and 7.0% had probable generalized anxiety disorder as measured by a score of ≥10 on the PHQ-9 and GAD-7, respectively. The mean scores on FCV-19S and PVD were 17.0 (6.6 SD) and 4.29 (1.02 SD), respectively.Telehealth use during COVID-19 has more than doubled. It is generally well regarded by respondents, although only a fourth of the SCI population has reported its use. With this in mind, it is important to understand the barriers to further adoption. In addition, higher rates of probable depression were seen than those estimated by pre-pandemic studies in other countries.

Reverse end-to-side (RETS) nerve transfer has become increasingly popular in patients with severe high ulnar nerve injury, but the reported outcomes have been inconsistent.To evaluate the "babysitting effect," we compared outcomes after anterior interosseous nerve RETS transfer with nerve decompression alone. To evaluate the source of regenerating axons, a group with end-to-end (ETE) transfer was used for comparisons.Electrophysiology measures were used to quantify the regeneration of anterior interosseous nerve (AIN) and ulnar nerve fibers while functional recovery was evaluated using key pinch and Semmes-Weinstein monofilaments. The subjects were followed postsurgically for 3 years.Sixty-two subjects (RETS = 25, ETE = 16, and decompression = 21) from 4 centers in Western Canada were enrolled. All subjects with severe ulnar nerve injury had nerve compression at the elbow except 10 in the ETE group had nerve laceration or traction injury. Postsurgically, no reinnervation from the AIN to the abductor digiti minimi muscles was seen in any of the RETS subjects. Although there was no significant improvement in compound muscle action potentials amplitudes and pressure detection thresholds in the decompression and RETS group, key pinch strength significantly improved in the RETS group ( P.05).The results from published clinical trials are conflicting in part because crossover regeneration from the donor nerve has never been measured. Unlike those with ETE nerve transfers, we found that there was no crossover regeneration in the RETS group. The extent of reinnervation was also no different from decompression surgery alone. Based on these findings, the justifications for this surgical technique need to be carefully re-evaluated.

Background: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date. Patients and methods: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions). Results: Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1. Conclusions: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.

Nerve transfer surgery (NT) constitutes an exciting option to improve upper limb functions in chronic spinal cord injury (SCI), but requires intact sublesional lower motor neuron (LMN) health. The purpose of this study was to characterize patterns of LMN abnormality in nerve-muscle groups that are the potential recipients of NT, using a standardized electrodiagnostic examination, in individuals with chronic SCI (injury duration2 years, injury levels C4-T1). The LMN abnormality was determined using a semihierarchical approach, combining the amplitude compound muscle action potential (CMAP) and abnormal spontaneous activity on needle electromyography (EMG). Ten participants (46 potential recipient muscles) were included (median age, 42.5 years; six males and four females; median duration from injury, 15.5 years). A high frequency of LMN abnormality was observed (87%), although there was substantial variation within and between individuals. No statistically significant discordance was observed between LMN abnormality on CMAP and EMG (

BackgroundBronchopulmonary dysplasia (BPD), its complication pulmonary hypertension (BPD-PH) and preterm brain and gut injury lead to significant morbidity and mortality in infants born extremely prematurely. There is extensive evidence that the pro-inflammatory cytokine interleukin 1 (IL-1) plays a key role in the pathophysiology of these illnesses. Two decades of clinical use in paediatric and adult medicine have established an excellent safety and efficacy record for IL-1 blockade with IL-1 receptor antagonist (IL-1Ra, medication name anakinra). Building on robust pre-clinical evidence, the Anakinra Pilot trial aims to demonstrate safety and feasibility of administering anakinra to preterm infants, and to establish pharmacokinetics in this population. Its ultimate goal is to facilitate large studies that will test whether anakinra can ameliorate early-life inflammation, thus alleviating multiple complications of prematurity.Methods and analysisAnakinra Pilot is an investigator-initiated, single arm, safety and feasibility dose-escalation trial in extremely preterm infants born between 24 weeks 0 days (240) and 276 weeks of gestational age (GA). Enrolled infants will receive anakinra intravenously over the first 21 days after birth, starting in the first 24 h after birth. In the first phase, dosing is 1 mg/kg every 48 h, and dosage will increase to 1.5 mg/kg every 24 h in the second phase. Initial anakinra dosing was determined through population pharmacokinetic model simulations. During the study, there will be a interim analysis to confirm predictions before undertaking dose assessment. Anakinra therapy will be considered safe if the frequency of adverse outcomes/events does not exceed that expected in infants born at 240-276 weeks GA.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT05280340.

In this review, we highlight the important role of the clinical electrodiagnostic (EDX) evaluation after cervical spinal cord injury (SCI). Our discussion focuses on the need for timely, frequent, and accurate EDX evaluations in the context of nerve transfer surgery to restore critical upper limb functions, including elbow extension, hand opening, and hand closing. The EDX evaluation is crucial to define the extent of lower motor neuron lesions and determine candidacy for surgery. We also discuss the important role of the postoperative EDX evaluation in determining prognosis and supporting rehabilitation. We propose a practical framework for EDX evaluation in this clinical setting.

Decision-making among adolescents and young adults with cancer (AYA) is often complex, ongoing, and multifaceted, involving caregiver and oncology provider perspectives. Engagement in decision-making against the backdrop of normative developmental processes of acquiring autonomy and gaining independence contributes to the complexity of decision-making. Semi-structured qualitative interviews from 11 AYA and caregiver dyads and eight oncology providers examined decision-making processes with specific attention to the role of shared decision-making, cognitive and emotional processes, and coping with the decision-making experience. Five decision-making patterns were identified, with collaborative decision-making and AYA-driven decisions most commonly described. Utilizing hypothesis coding, AYA and caregivers explained how cognitive (i.e., pros/cons) and emotional (i.e., shock and fear of missing out) processes influenced cancer-related decisions. Coping strategies provided clarity and respite when engaged in decision-making. Our findings illuminate important implications for how to best support decision-making among AYA and caregivers, including the role oncology providers can play during decision-making.

Peripheral nerve injury (PNI) can result in devastating loss of function, often with poor long-term prognosis. Increased use of peripheral nerve surgical techniques (eg, nerve transfer, nerve grafting, and nerve repair) has resulted in improved muscle strength and other functional outcomes in patients with PNI. Muscle strength has largely been evaluated with the British Medical Research Council (MRC) scale. MRC is convenient to use in clinical settings, but more robust measures of muscle function are necessary to fully elucidate patient recovery. This scoping review aims to examine alternative instruments used to assess muscle function in studies of peripheral nerve surgery for PNI of the upper and lower limbs. A scoping review was conducted using Ovid MEDLINE, CINAHL, EMBASE, and PubMed databases in May and December of 2020, yielding a total of 20 studies pertaining to the review question. Studies pertaining to handheld dynamometry, grip and pinch dynamometry, Rotterdam Intrinsic Hand Myometers, isokinetic dynamometry, ultrasonography, and electromyography were reviewed. We provide a synopsis of each method and current clinical applications and discuss potential benefits, disadvantages, and areas of future research.

Objective: To determine the test-retest reliability of quantitative and qualitative baroreflex sensitivity (BRS) parameters derived from the Valsalva maneuver (VM) in individuals with traumatic cervical SCI. Design: Test-retest reliability. Setting: Tertiary rehabilitation center. Participants: Fourteen participants with cervical SCI (ranging from C3-C8 neurological level). Outcome Measurements: Beat-to-beat systolic blood pressure (SBP) traces (finger photoplethysmography) were obtained during a 15-second forced expiration at two time points (7.6 ± 2.9 days between sessions) to assess VM reliability. Test-retest reliability of BRS metrics from derived from the VM (Valsalva ratio; VR, pressure recovery time; PRT, vagal baroreflex sensitivity; BRSv, adrenergic baroreflex sensitivity; BRSa(1), and total recovery; TR) were assessed by intra-class correlation coefficient (ICC, with 95% confidence interval; CI) and by qualitative reproducibility (V, N, or M pattern). Results: ICCs for quantitative parameters were (CI): VR = 0.894 (0.703–0.965), TR = 0.927 (0.789–0.976), BRSa(1) = 0.561 (0.149–0.911), PRT = 0.728 (0.343–0.904), BRSv = 0.243 (−0.309–0.673). Qualitatively, 12 subjects (85.7%) demonstrated reproducible VM patterns at both time points (3 “M” pattern, 8 “V” pattern and one “N” pattern). Conclusion: VR (a measure of cardiovagal function) and TR (a measure of sympathetic adrenergic function) are reliable quantitative parameters that can be derived from SBP response to VM in participants with SCI. Qualitative waveform analysis was reproducible in 12/14 participants. This provides the foundational evidence required to pursue further validity testing to establish a role for VM in the assessment of autonomic functions in SCI.

Nerve transfer surgery for patients with nerve and spinal cord injuries can result in dramatic functional improvements. As a result, interdisciplinary complex nerve injury programs (CNIPs) have been established in many Canadian centers, providing electrodiagnostic and surgical consultations in a single encounter. We sought to determine which allied health care services are included in Canadian CNIPs, at the 3rd Annual Canadian Peripheral Nerve Symposium. Twenty CNIPs responded to a brief survey and reported access as follows: occupational therapy = 60%, physiotherapy = 40%, social work = 20%, and mental health = 10%. Access to allied health services is variable in CNIPs across Canada, possibly resulting in heterogeneity in patient care.

The role of the cerebellum in motor control has been investigated extensively, but its contribution to the muscle pattern organization underlying goal-directed movements is still not fully understood. Muscle synergies may be used to characterize multimuscle pattern organization irrespective of time (spatial synergies), in time irrespective of the muscles (temporal synergies), and both across muscles and in time (spatiotemporal synergies). The decomposition of muscle patterns as combinations of different types of muscle synergies offers the possibility to identify specific changes due to neurological lesions. In this study, we recorded electromyographic activity from 13 shoulder and arm muscles in subjects with cerebellar ataxias (CA) and in age-matched healthy subjects (HS) while they performed reaching movements in multiple directions. We assessed whether cerebellar damage affects the organization of muscle patterns by extracting different types of muscle synergies from the muscle patterns of each HS and using these synergies to reconstruct the muscle patterns of all other participants. We found that CA muscle patterns could be accurately captured only by spatial muscle synergies of HS. In contrast, there were significant differences in the reconstruction R2 values for both spatiotemporal and temporal synergies, with an interaction between the two synergy types indicating a larger difference for spatiotemporal synergies. Moreover, the reconstruction quality using spatiotemporal synergies correlated with the severity of impairment. These results indicate that cerebellar damage affects the temporal and spatiotemporal organization, but not the spatial organization, of the muscle patterns, suggesting that the cerebellum plays a key role in shaping their spatiotemporal organization.NEW & NOTEWORTHY In recent studies, the decomposition of muscle activity patterns has revealed a modular organization of the motor commands. We show, for the first time, that muscle patterns of subjects with cerebellar damage share with healthy controls spatial, but not temporal and spatiotemporal, modules. Moreover, changes in spatiotemporal organization characterize the severity of the subject's impairment. These results suggest that the cerebellum has a specific role in shaping the spatiotemporal organization of the muscle patterns.

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3 + CD4 + T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.

Humans have a remarkable capacity to learn new motor skills, a process that requires novel muscle activity patterns. Muscle synergies may simplify the generation of muscle patterns through the selection of a small number of synergy combinations. Learning new motor skills may then be achieved by acquiring novel muscle synergies. In a previous study, we used myoelectric control to construct virtual surgeries that altered the mapping from muscle activity to cursor movements. After compatible virtual surgeries, which could be compensated by recombining subject-specific muscle synergies, participants adapted quickly. In contrast, after incompatible virtual surgeries, which could not be compensated by recombining existing synergies, participants explored new muscle patterns, but failed to adapt. Here, we tested whether task space exploration can promote learning of novel muscle synergies, required to overcome an incompatible surgery. Participants performed the same reaching task as in our previous study, but with more time to complete each trial, thus allowing for exploration. We found an improvement in trial success after incompatible virtual surgeries. Remarkably, improvements in movement direction accuracy after incompatible surgeries occurred faster for corrective movements than for the initial movement, suggesting that learning of new synergies is more effective when used for feedback control. Moreover, reaction time was significantly higher after incompatible than after compatible virtual surgeries, suggesting an increased use of an explicit adaptive strategy to overcome incompatible surgeries. Taken together, these results indicate that exploration is important for skill learning and suggest that human participants, with sufficient time can learn new muscle synergies.NEW & NOTEWORTHYMotor skill learning requires the acquisition of novel muscle patterns, a slow adaptive process. Here we show that learning to control a cursor after an incompatible virtual surgery, a complex skill requiring new muscle synergies, is possible when enough time for task space exploration is provided. Our results suggest that learning new synergies is related to the exceptional human capacity to acquire a wide variety of novel motor skills with practice.

Loss of upper extremity function following spinal cord injury (SCI) can have devastating consequences on quality of life. Peripheral nerve transfer surgery aims to restore motor control of upper extremities following cervical SCI and is poised to revolutionize surgical management in this population. The surgery involves dividing an expendable donor nerve above the level of the spinal lesion and coapting it to a recipient nerve arising from the lesional or infralesional segment of the injured cord. In order to maximize outcomes in this complex patient population, refinements in surgical technique need to be integrated with principles of spinal cord medicine and basic science. Deciding on the ideal timing of nerve transfer surgery is one aspect of care that is critical to maximizing recovery and has received very little attention to date in the literature. This complex topic is reviewed, with a focus on expectations for spontaneous recovery within upper motor neuron components of the injury, balanced against the need for expeditious re-innervation for lower motor neuron elements of the injury. The discussion also considers the case of a patient with C6 motor complete SCI in whom myotomes without electrodiagnostic evidence of denervation spontaneously improved by 6 months post-injury, thereby adjusting the surgical plan. The relevant concepts are integrated into a clinical algorithm with recommendations that consider maximal opportunity for spontaneous clinical improvement post-injury while avoiding excessive delays that may adversely affect patient outcomes.

The coronavirus pandemic (COVID-19) is predicted to increase burnout in health professionals (HPs), but little is known about moral injury (MI) in this context. We administered the Moral Injury Symptoms Scale for Health Professionals (MISS-HP) and the abbreviated Maslach Burnout Inventory via online survey to a global sample of 1831 HPs in April and October 2020. Mean MISS-HP increased from 27.4 (SD, 11.6) in April to 36.4 (SD, 13.8) in October (p0.001), with an accompanying increase in personal accomplishment (April: 4.7; SD, 3.1; October: 9.3; SD, 3.1; p0.001) and no change in other burnout subscales. In April, 26.7% of respondents reported at least moderate functional impairment from MI, increasing to 45.7% in October (p0.001). Predictors of MISS-HP included younger age and being a nurse. Odds of functional impairment were higher in respondents who were widowed, divorced, never married, or had direct experience caring for patients with COVID-19. COVID-19 has increased MI but not burnout in HPs; younger or unmarried individuals, nurses, and frontline workers may benefit from targeted outreach to reduce downstream effects of MI, depression, and/or posttraumatic stress disorder.

The use of smartphone apps is an essential part of everyday life. Mobile applications offer enormous opportunities for dealing with challenges in public health, and their number increases every day. This paper aims to review the existing literature on mobile applications in orthopaedic oncology and to summarize the current mobile applications for musculoskeletal tumors. A systematic literature review was conducted regarding articles on mobile applications in orthopaedic and trauma surgery. The focus was on identifying mobile applications that can be used in the treatment of patients with musculoskeletal tumors. Two reviewers independently assessed study eligibility, extracted data, and appraised methodological quality. In addition, the Apple App Store and Google Play Store were searched for suitable mobile applications. Ninety-one articles describing a mobile application in orthopaedic and trauma surgery were identified. Three articles focused on a mobile application for musculoskeletal tumors. Additionally, seven mobile applications were available in the App/Play Stores dealing with bone or soft tissue tumors in orthopaedic oncology without corresponding scientific articles. Increasing numbers of mobile applications are being developed in orthopaedic and trauma surgery. Currently, only three scientific articles on mobile applications in orthopaedic oncology are present, yet several more applications are available without scientific medical evaluation. Since mobile applications can facilitate the everyday life of orthopaedic and trauma surgeons, it is worthwhile to be aware of new developments in this field. A regular scientific evaluation of the subject is important in order to classify the significance of these applications. Supplementary information The online version contains supplementary material available at 10.1007/s10916-021-01774-z.

In adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal instrumented fusion (PSIF), we aimed to answer these questions: (1) is there a difference in postoperative urinary retention (UR) rates among patients who had removal of their Foley catheters before vs. after discontinuation of epidural analgesia (EA)? (2) Can the timing of Foley catheter removal be an independent risk factor for postoperative UR requiring recatheterization? (3) Is there an incurred cost related to treating UR?Retrospective cohort.EA has been widely used for postoperative pain control after PSIF for AIS. In these patients, removing the Foley catheter, inserted for intraoperative monitoring of urine output, is indicated in the early postoperative period. However, a controversy exists as to whether it should be removed before or after the EA has been discontinued.A single-institution, longitudinally maintained database was queried to identify 297 patients who met specific inclusion and exclusion criteria. Patient characteristics and the order and timing of removing the urinary and epidural catheters were collected. Rates of UR were statistically compared in patients who had early vs. late urinary catheter removal. A univariate and multivariate regression analysis was conducted to identify independent risk factors. Hospital episode costs were analyzed.Patients who had early (n = 66, 22%) vs. late (n = 231, 78%) urinary catheter removal had a significantly higher incidence of UR requiring recatheterization (15 vs. 4.7%, p = 0.007). Patient with early removal were almost 4 times more likely to develop UR requiring recatheterization [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.5-9.7, p = 0.005]. UR incurred additional costs averaging $15,000/patient (p = 0.204).In patients who had PSIF for AIS, removal of a urinary catheter before discontinuation of EA is an independent risk factor for UR, requiring recatheterization and associated with increased cost.III.

Clinically, increased breast tumor stiffness is associated with metastasis and poorer outcomes. Yet, in vitro studies of tumor cells in 3D scaffolds have found decreased invasion in stiffer environments. To resolve this apparent contradiction, MDA-MB-231 breast tumor spheroids were embedded in ‘low’ (2 kPa) and ‘high’ (12 kPa) stiffness 3D hydrogels comprised of methacrylated gelatin/collagen I, a material that allows for physiologically-relevant changes in stiffness while matrix density is held constant. Cells in high stiffness materials exhibited delayed invasion, but more abundant actin-enriched protrusions, compared to those in low stiffness. We find that cells in high stiffness had increased expression of Mena, an invadopodia protein associated with metastasis in breast cancer, as a result of EGFR and PLCγ1 activation. As invadopodia promote invasion through matrix remodeling, we examined matrix organization and determined that spheroids in high stiffness displayed a large fibronectin halo. Interestingly, this halo did not result from increased fibronectin production, but rather from Mena/α5 integrin dependent organization. In high stiffness environments, FN1 knockout inhibited invasion while addition of exogenous cellular fibronectin lessened the invasion delay. Analysis of fibronectin isoforms demonstrated that EDA-fibronectin promoted invasion and that clinical invasive breast cancer specimens displayed elevated EDA-fibronectin. Combined, our data support a mechanism by which breast cancer cells respond to stiffness and render the environment conducive to invasion. More broadly, these findings provide important insight on the roles of matrix stiffness, composition, and organization in promoting tumor invasion.

Here we present the case of SP, a 21-year-old female with life-long dyscalculia. SP was subsequently diagnosed with grapheme-color synesthesia, a diagnosis that serendipitously catalyzed our development of a novel aid:The digit-color calculator (DCC). The DCC substantiates SP's color

Studies in the U.S. and Mexico have observed the clustering of food resources around schools, which may promote the use of these resources. Our study characterized and compared school neighborhood food environments in Guadalajara, Jalisco, and Houston, Texas, and examined socioeconomic disparities in food resource availability across school neighborhoods. We used the Goods and Services Inventory to document the frequency and type of resources within each school neighborhood. School neighborhoods in Guadalajara had significantly more food resources than those in Houston. We found that convenience stores and table service restaurants were the most prevalent food resources in school neighborhoods in both cities. Guadalajara school neighborhoods had a higher prevalence of supermarkets and grocery stores than Houston. Low-income school neighborhoods in Guadalajara with poorly educated residents had significantly more food carts than high-income neighborhoods with more educated residents. In Houston, we found significantly more fast food restaurants and convenience stores in school neighborhoods with more educated residents than school neighborhoods with less educated residents. The influence of food resources within school neighborhoods on the dietary habits of schoolchildren should be further explored in both the U.S. and Mexico. The characterization of school neighborhood food environments can inform policymakers, city planners, and school officials who seek to implement policies to create healthier food environments.

Ultrasound is a uniquely valuable tool for evaluating musculoskeletal problems in the pediatric hand. Acute and chronic injuries involving tendons and ligaments of the hand can be quickly assessed and can guide surgical decision-making. Using ultrasound, palpable lesions and masses can be evaluated for cystic and solid components aiding in differential diagnosis. Additionally, ultrasound provides evaluation of acute versus chronic changes of inflammatory arthritis, assessing disease severity and subclinical synovitis and serving as an adjunct to medical management. This review will cover common indications and ultrasound findings of the pediatric hand, focusing on common injuries, inflammatory arthritis and masses. Important anatomical features of the hand will be discussed as well as imaging technique and evaluation in the pediatric patient.

Introduction Supplemental data from the 2019 National Blood Collection and Utilization Survey (NBCUS) are presented and include findings on donor characteristics, autologous and directed donations and transfusions, platelets (PLTs), plasma and granulocyte transfusions, pediatric transfusions, transfusion-associated adverse events, cost of blood units, hospital policies and practices, and implementation of blood safety measures, including pathogen reduction technology (PRT). Methods National estimates were produced using weighting and imputation methods for a number of donors, donations, donor deferrals, autologous and directed donations and transfusions, PLT and plasma collections and transfusions, a number of crossmatch procedures, a number of units irradiated and leukoreduced, pediatric transfusions, and transfusion-associated adverse events. Results Between 2017 and 2019, there was a slight decrease in successful donations by 1.1%. Donations by persons aged 16-18 decreased by 10.1% while donations among donors >65 years increased by 10.5%. From 2017 to 2019, the median price paid for blood components by hospitals for leukoreduced red blood cell units, leukoreduced apheresis PLT units, and for fresh frozen plasma units continued to decrease. The rate of life-threatening transfusion-related adverse reactions continued to decrease. Most whole blood/red blood cell units (97%) and PLT units (97%) were leukoreduced. Conclusion Blood donations decreased between 2017 and 2019. Donations from younger donors continued to decline while donations among older donors have steadily increased. Prices paid for blood products by hospitals decreased. Implementation of PRT among blood centers and hospitals is slowly expanding.

the novel Coronavirus SARS-CoV-2 is suspected of acting as a trigger for autoimmune diseases and the production of autoantibodies. Retinoic acid-inducible gene (RIG)-I-like receptors (RLR), including melanoma differentiation-associated protein 5 (MDA5) and RIG-I, recognize the double-strand (ds) virus RNA and induce the production of Type I interferon (Type I IFN) as well as pro-inflammatory cytokines like Interleukin (IL)-6.

Young adult cancer survivors often experience altered social relationships which may be a result of social support networks not knowing how to effectively provide the support young adults need. This study aimed to identify and describe themes of young adults' support preferences when engaging in cancer-related conversations and examine whether psychological distress is associated with support-related preferences.Young adult survivors (Listening (81.4%) was most commonly preferred; showing pity/worry (33.9%) was most undesired. Other types of preferred support included empathy, validation, encouragement (42.4%), and honest conversation (23.7%); common types of undesirable support included being uninterested and changing the subject (32.3%), insensitive comments and questions (25.4%), and negative stories/personal comparisons (23.7%). Greater depressive symptoms (OR = 1.21,Study findings can inform communication interventions and educate support networks about types of support young adults prefer when discussing cancer-related concerns.

INTRODUCTION: Previous iterations of National Blood Collection and Utilization Survey (NBCUS) have demonstrated declines in blood collection and transfusion in the United States since 2008, including declines of 3.0% and 6.1% in red blood cell (RBC) collections and transfusions between 2015 and 2017, respectively. This study describes results of the 2019 NBCUS. METHODS: The survey was distributed to all US blood collection centers, all hospitals performing ≥1000 surgeries annually, and a 40% random sample of hospitals performing 100–999 surgeries annually. Weighting and imputation were used to generate national estimates for units of blood and components collected, distributed, transfused, and outdated. RESULTS: In 2019, 11,590,000 RBC units were collected (95% confidence interval [CI], 11,151,000–12,029,000 units), a 5.1% decrease compared with 2017, while 10,852,000 RBC units were transfused (95% CI, 10,444–11,259 units), a 2.5% increase from 2017. Between 2017 and 2019, platelet distributions (2,508,000 units; 95% CI, 2,375,000–2,641,000 units) decreased by 2.0%, and plasma distributions (2,679,000 units; 95% CI, 2,525,000–2,833,000 units) decreased by 16.5%. During the same time period, platelet transfusions (2,243,000 units; 95% CI, 1,846,000–2,147,000 units) increased by 15.8% and plasma transfusions (2,185,000 units; 95% CI, 2,068,000–2,301,000 units) decreased by 8.0%. CONCLUSION: Utilization of RBC in the United States might have reached a nadir. Between 2017 and 2019, RBC collections declined while RBC transfusions did not significantly change, suggesting a narrowing between blood supply and demand. Monitoring national blood collection and utilization data is integral to understanding trends in blood supply safety and availability.

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment.

This work was supported by the Wellcome Trust (grant number 206194); the Biotechnology and Biological Sciences Research Council, the Department for International Development, the Economic & Social Research Council, the Medical Research Council, the Natural Environment Research Council and the Defence Science & Technology Laboratory, under the Zoonoses and Emerging Livestock Systems (ZELS) programme (grant number BB/L018985/1 to JPW and MS and grant number BB/S013822/1 to JPW, MS and NDD). FA, AE and MR received funding from the Wellcome Trust (grant number 104958/Z/14/Z). Hybridization between different species of parasites is increasingly being recognised as a major public and veterinary health concern at the interface of infectious diseases biology, evolution, epidemiology and ultimately control. Recent research has revealed that viable hybrids and introgressed lineages between Schistosoma spp. are prevalent across Africa and beyond, including those with zoonotic potential. However, it remains unclear whether these hybrid lineages represent recent hybridization events, suggesting hybridization is ongoing, and/or whether they represent introgressed lineages derived from ancient hybridization events. In human schistosomiasis, investigation is hampered by the inaccessibility of adult-stage worms due to their intravascular location, an issue which can be circumvented by post-mortem of livestock at abattoirs for Schistosoma spp. of known zoonotic potential. To characterise the composition of naturally-occurring schistosome hybrids, we performed whole-genome sequencing of 21 natural livestock infective schistosome isolates. To facilitate this, we also assembled a de novo chromosomal-scale draft assembly of Schistosoma curassoni. Genomic analyses identified isolates of S. bovis, S. curassoni and hybrids between the two species, all of which were early generation hybrids with multiple generations found within the same host. These results show that hybridization is an ongoing process within natural populations with the potential to further challenge elimination efforts against schistosomiasis. Publisher PDF

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant., Graphical Abstract, Highlights • Increasing frequency of SARS-CoV-2 D614G is consistent with a selective advantage • Phylodynamic analyses do not show significantly different growth of D614G clusters • There is no association of D614G replacement with greater severity of infection • The D614G replacement is associated with higher viral loads and younger patient age, Analysis of the spread and frequency of SARS-CoV-2 D614G in the United Kingdom suggests a selective advantage for this strain that is associated with higher viral loads in younger patients but not higher COVID-19 clinical severity or mortality.

The design of myocontrolled devices faces particular challenges in children with dyskinetic cerebral palsy because the electromyographic signal for control contains both voluntary and involuntary components. We hypothesized that voluntary and involuntary components of movements would be uncorrelated and thus detectable as different synergistic patterns of muscle activity, and that removal of the involuntary components would improve online EMG-based control. Therefore, we performed a synergy-based decomposition of EMG-guided movements, and evaluated which components were most controllable using a Fitts’ Law task. Similarly, we also tested which muscles were most controllable. We then tested whether removing the uncontrollable components or muscles improved overall function in terms of movement time, success rate, and throughput. We found that removal of less controllable components or muscles did not improve EMG control performance, and in many cases worsened performance. These results suggest that abnormal movement in dyskinetic CP is consistent with a pervasive distortion of voluntary movement rather than a superposition of separable voluntary and involuntary components of movement.

Bone fragility and fracture risk are assessed by measuring the areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). While aBMD correlates with bone strength, it is a poor predictor of fragility fracture risk. Alternatively, fracture toughness assesses the bone’s resistance to crack propagation and fracture, making it a suitable bone quality metric. Here, we explored how femoral midshaft measurements from DXA, micro-computed tomography (μCT), and Raman spectroscopy could predict fracture toughness. We hypothesized that ovariectomy (OVX) decreases aBMD and fracture toughness compared to controls and we can optimize a multivariate assessment of bone quality by combining results from X-ray and Raman spectroscopy. Female mice underwent an OVX (n=5) or sham (n=5) surgery at 3 months of age. Femurs were excised 3 months after ovariectomy and assessed with Raman spectroscopy, μCT, and DXA. Subsequently, a notch was created on the anterior side of the mid-diaphysis of the femurs. Three-point bending induced a controlled fracture that initiated at the notch. The OVX mice had a significantly lower aBMD, cortical thickness, and fracture toughness when compared to controls (p2=0.71, p2=0.92, p

Summary The recommendations in this report supersede the U.S Public Health Service (PHS) guideline recommendations for reducing transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) through organ transplantation (Seem DL, Lee I, Umscheid CA, Kuehnert MJ. PHS guideline for reducing human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Rep 2013;128:247–343), hereafter referred to as the 2013 PHS guideline. PHS evaluated and revised the 2013 PHS guideline because of several advances in solid organ transplantation, including universal implementation of nucleic acid testing of solid organ donors for HIV, HBV, and HCV; improved understanding of risk factors for undetected organ donor infection with these viruses; and the availability of highly effective treatments for infection with these viruses. PHS solicited feedback from its relevant agencies, subject-matter experts, additional stakeholders, and the public to develop revised guideline recommendations for identification of risk factors for these infections among solid organ donors, implementation of laboratory screening of solid organ donors, and monitoring of solid organ transplant recipients. Recommendations that have changed since the 2013 PHS guideline include updated criteria for identifying donors at risk for undetected donor HIV, HBV, or HCV infection; the removal of any specific term to characterize donors with HIV, HBV, or HCV infection risk factors; universal organ donor HIV, HBV, and HCV nucleic acid testing; and universal posttransplant monitoring of transplant recipients for HIV, HBV, and HCV infections. The recommendations are to be used by organ procurement organization and transplant programs and are intended to apply only to solid organ donors and recipients and not to donors or recipients of other medical products of human origin (e.g., blood products, tissues, corneas, and breast milk). The recommendations pertain to transplantation of solid organs procured from donors without laboratory evidence of HIV, HBV, or HCV infection. Additional considerations when transplanting solid organs procured from donors with laboratory evidence of HCV infection are included but are not required to be incorporated into Organ Procurement and Transplantation Network policy. Transplant centers that transplant organs from HCV-positive donors should develop protocols for obtaining informed consent, testing and treating recipients for HCV, ensuring reimbursement, and reporting new infections to public health authorities.

BACKGROUND: Serious transfusion-associated adverse events are rare in the United States. To enhance blood safety, various measures have been developed. With use of data from the 2017 National Blood Collection and Utilization Survey (NBCUS), we describe the rate of transfusion-associated adverse events and the implementation of specific blood safety measures. STUDY DESIGN AND METHODS: Data from the 2017 NBCUS were used with comparison to already published estimates from 2015. Survey weighting and imputation were used to obtain national estimates of transfusion-associated adverse events, and the number of units treated with pathogen reduction technology (PRT), screened for Babesia, and leukoreduced. RESULTS: The rate of transfusion-associated adverse events requiring any diagnostic or therapeutic interventions was stable (275 reactions per 100,000 transfusions in 2015 and 282 reactions per 100,000 transfusions in 2017). In 2017 among US blood collection centers, 16 of 141 (11.3%) reported screening units for Babesia and 28 of 144 (19.4%) reported PRT implementation; 138 of 2279 (6.1%) hospitals reported transfusing PRT-treated platelets. In 2017, 134 of 2336 (5.7%) hospitals reported performing secondary bacterial testing of platelets (50,922 culture-based and 63,220 rapid immunoassay tests); in 2015, 71 of 1877 (3.8%) hospitals performed secondary testing (87,155 culture-based and 21,779 rapid immunoassay tests). Nearly all whole blood/red blood cell units and platelet units were leukoreduced. CONCLUSIONS: Besides leukoreduction, implementation of most blood safety measures reported in this study remains low. Nationally, hospitals might be shifting from culture-based secondary bacterial testing to rapid immunoassays.

Introduction This report provides supplemental results from the 2017 National Blood Collection and Utilization Survey on characteristics of the donor population, autologous and directed donations and transfusions, platelets, plasma and granulocyte transfusions, pediatric transfusions, severe donor-related adverse events, cost of blood units, hospitals policies and practices, and inventory, dosing, and supply. Methods Weighting and imputation were used to generate national estimates including number of donors, donations, donor deferrals, autologous and directed donations and transfusions, severe donor-related adverse events, platelet and plasma collections and transfusions, number of cross-match procedures, irradiation and leukoreduction, and pediatric transfusions. Results Between 2015 and 2017, successful donations decreased slightly by 2.1% with a 10.3% decrease in donations by persons aged 16-18 years and a 14.4% increase in donations by donors aged >65 years. The median price paid for blood components by hospitals decreased from $211 to $207 for leukoreduced red blood cell units, from $523 to $517 for leukoreduced apheresis platelet units, and from $54 to $51 for fresh frozen plasma units. Plasma transfusions decreased 13.6%, but group AB plasma units transfused increased 24.7%. Conclusion Between 2015 and 2017, blood donations declined slightly because of decreases in donations from younger donors, but the number of donations from older donors increased. The price hospitals pay for blood has continued to decrease. Plasma transfusions have decreased, but the proportion of plasma transfusions involving group AB plasma have increased.

Multiple recent reports have indicated a rising awareness of trunnionosis-related implant failures, accounting for up to 3% of all total hip arthroplasty revisions. Moreover, aseptic loosening and osteolysis from local release of metal debris can be the presenting manifestations, and thus the true incidence of trunnionosis is thought to be underreported. Furthermore, the relatively unclear and multifactorial pathogenesis and the widely variable clinical presentations pose a diagnostic challenge. A consensus regarding the ideal intervention and its timing is also lacking. Because of the relative paucity of reports regarding the diagnosis and management of trunnionosis, we conducted this evidence-based review to evaluate the (1) incidence, (2) pathogenesis, (3) diagnosis, and (4) treatment of trunnionosis in metal-on-polyethylene total hip arthroplasty. We then propose an algorithm for the diagnostic work-up and management of this condition.

Key Points Question How did health care workers experience moral injury during the COVID-19 pandemic before the availability of vaccines? Findings In this qualitative study of 1344 health care professionals in 2020, respondents reported significant changes in their personal and professional lives during the course of the pandemic. Common themes were feeling isolated from non–health care professionals, alienated from patients, and betrayed by coworkers, administrators, and the public. Meaning Moral injury can result from chronic stressors in morally injurious environments; leadership must identify and address these stressors to effectively support health care professionals as COVID-19 continues to strain staff’s physical, mental, and emotional resources., This qualitative study explores the factors associated with moral injury for health care workers who were involved in patient care during the COVID-19 pandemic in 2020, prior to the availability of vaccines., Importance Moral injury in health care professionals (HPs) has worsened over the course of the COVID-19 pandemic. The trauma and burnout associated with moral injury has profound implications for the mental health of HPs. Objective To explore the potential factors associated with moral injury for HPs who were involved in patient care during the COVID-19 pandemic in 2020, prior to the availability of vaccines. Design, Setting, and Participants In this qualitative study, HPs were actively recruited to participate in a survey via snowball sampling via email and social media in 2 phases of 5 weeks each: April 24 to May 30, 2020 (phase 1), and October 24 to November 30, 2020 (phase 2). Overall, 1831 respondents answered demographic questions and assessments for moral injury, intrinsic religiosity, and burnout. Of those, 1344 responded to the open-ended questions. Responses to open-ended questions were coded iteratively and thematically analyzed within the framework of moral injury. Exposures Working in a patient care setting during the COVID-19 pandemic prior to the availability of vaccines. Main Outcomes and Measures Inductive thematic analysis of open-response survey answers identified dominant emotions and common stressors associated with moral injury. Results There were 335 individuals (109 [32.6%] aged 35-44 years; 288 [86.0%] women; 294 [87.8%] White) in phase 1 and 1009 individuals (384 [38.1%] aged 35-44 years; 913 [90.5%] women; 945 [93.7%] White) in phase 2. In phase 1, the respondents were predominantly nurses (100 [29.9%]), physicians (78 [23.3%]), advanced practice practitioners (APPs) (70 [20.9%]), and chaplains (55 [16.4%]). In phase 2, the respondents were predominantly nurses (589 [58.4%]), physicians (114 [11.3%]), and APPs (104 [10.3%]). HPs faced numerous stressors, such as fear of contagion, stigmatization, short-staffing, and inadequate personal protective equipment. The emotions experienced were (1) fear in phase 1, then fatigue in phase 2; (2) isolation and alienation; and (3) betrayal. Conclusions and Relevance These findings suggest that HPs experienced moral injury during the COVID-19 pandemic. Moral injury was not only experienced after a single moral dilemma but also from working in morally injurious environments. These experiences can serve as potential starting points for organizations to engender and enhance organizational and individual recovery, team building, and trust. System-level solutions that address shortages in staffing and personal protective equipment are needed to promote HP well-being.

Synaesthesia refers to a diverse group of perceptions. These unusual perceptions are defined by the experience of concurrents; these are conscious experiences that are catalysed by attention to some normally unrelated stimulus, the inducer. In grapheme-colour synaesthesia numbers, letters, and words can all cause colour concurrents, and these are independent of the actual colour with which the graphemes are displayed. For example, when seeing the numeral ‘3’ a person with synaesthesia might experience green as the concurrent irrespective of whether the numeral is printed in blue, black, or red. As a trait, synaesthesia has the potential to cause both positive and negative effects. However, regardless of the end effect, synaesthesia incurs an initial cost when compared with its equivalent example from normal perception; this is the additional processing cost needed to generate the information on the concurrent. We contend that this cost can be reduced by mirroring the concurrent in the environment. We designed the Digital-Colour Calculator (DCC) app, allowing each user to personalise and select the colours with which it displays its digits; it is the first reported example of a device/approach that leverages the concurrent. In this article we report on the reactions to the DCC for a sample of fifty-three synaesthetes and thirty-five non-synaesthetes. The synaesthetes showed a strong preference for the DCC over its normal counterpart. The non-synaesthetes showed no obvious preference. When using the DCC a subsample of the synaesthete group showed consistent improvement in task speed (around 8%) whereas no synaesthete showed a decrement in their speed.

Bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension (BPD-PH) are chronic inflammatory cardiopulmonary diseases with devastating short- and long-term consequences for infants born prematurely. The immature lungs of preterm infants are ill-prepared to achieve sufficient gas exchange, thus usually necessitating immediate commencement of respiratory support and oxygen supplementation. These therapies are life-saving, but they exacerbate the tissue damage that is inevitably inflicted on a preterm lung forced to perform gas exchange. Together, air-breathing and necessary therapeutic interventions disrupt normal lung development by aggravating pulmonary inflammation and vascular remodelling, thus frequently precipitating BPD and PH via an incompletely understood pathogenic cascade. BPD and BPD-PH share common risk factors, such as low gestational age at birth, fetal growth restriction and perinatal maternal inflammation; however, these risk factors are not unique to BPD or BPD-PH. Occurring in 17-24% of BPD patients, BPD-PH substantially worsens the morbidity and mortality attributable to BPD alone, thus darkening their outlook; for example, BPD-PH entails a mortality of up to 50%. The absence of a safe and effective therapy for BPD and BPD-PH renders neonatal cardiopulmonary disease an area of urgent unmet medical need. Besides the need to develop new therapeutic strategies, a major challenge for clinicians is the lack of a reliable method for identifying babies at risk of developing BPD and BPD-PH. In addition to discussing current knowledge on pathophysiology, diagnosis and treatment of BPD-PH, we highlight emerging biomarkers that could enable clinicians to predict disease-risk and also optimise treatment of BPD-PH in our tiniest patients.

The aim of this study was to characterize autonomic lesions in participants with spinal cord injury (SCI; n = 10) using an autonomic reflex screen, incorporating sudomotor, cardiovagal, and sympathetic adrenergic tests, as well as hemodynamic responses to head-up tilt (HUT). Hemodynamic responses were compared to healthy controls (n = 20) and previously published normative cutoffs in order better identify autonomic impairments. Sympathetic skin responses (SSRs), heart rate response to deep breathing (HRDB), and heart rate and beat-to-beat blood pressure responses to Valsalva maneuver (VM) and HUT were measured. SCI participants demonstrated impairment in at least one domain, with 7 of 10 demonstrating autonomic impairment across all domains. No single test was concordant with orthostatic hypotension on HUT, in all participants. Measures of cardiovagal function, including HRDB (SCI = 7.7 ± 3.8 beats/min vs. controls = 17.6 ± 8.1 beats/min) and Valsalva ratio (SCI = 1.53 ± 0.29 vs. controls = 1.85 ...

Case We present a case report of an 18-year-old woman who presented to a general surgeon with a several month history of intermittent right upper quadrant pain, strongly suggestive of symptomatic cholelithiasis and underwent a laparoscopic cholecystectomy. She was eventually found to have an osteoid osteoma (OO) of the right eighth rib. She was treated with radiofrequency ablation with complete resolution of symptoms 1 month after treatment. Conclusions In cases where a patient's age and risk factors would make the diagnosis of cholelithiasis less likely, OO should be added to the differential diagnosis of symptomatic right upper quadrant pain.

Single-cell RNA-sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation without prior knowledge has remained challenging. Here we describe a simple yet robust determinant of developmental potential—the number of detectably expressed genes per cell— and leverage this measure of transcriptional diversity to develop a new framework for predicting ordered differentiation states from scRNA-seq data. When evaluated on ~150,000 single-cell transcriptomes spanning 53 lineages and five species, our approach, called CytoTRACE, outperformed previous methods and ~19,000 molecular signatures for resolving experimentally-confirmed developmental trajectories. In addition, it enabled unbiased identification of tissue-resident stem cells, including cells with long-term regenerative potential. When used to analyze human breast tumors, we discovered candidate genes associated with less-differentiated luminal progenitor cells and validated GULP1 as a novel gene involved in tumorigenesis. Our study establishes a key RNA-based correlate of developmental potential and provides a new platform for robust delineation of cellular hierarchies (https://cytotrace.stanford.edu).

Publicly-available genetic databases promote data sharing and fuel scientific discoveries for the prevention, treatment, and management of disease. In 2018, we built Color Data, a user-friendly, open access database containing genotypic and self-reported phenotypic information from 50,000 individuals who were sequenced for 30 genes associated with hereditary cancer. In a continued effort to promote access to these types of data, we launched Color Data v2, an updated version of the Color Data database. This new release includes additional clinical genetic testing results from more than 18,000 individuals who were sequenced for 30 genes associated with hereditary cardiovascular conditions, as well as polygenic risk scores for breast cancer, coronary artery disease, and atrial fibrillation. In addition, we used self-reported phenotypic information to implement the following four clinical risk models: Gail Model for five-year risk of breast cancer, Claus Model for lifetime risk of breast cancer, simple office-based Framingham Coronary Heart Disease Risk Score for ten-year risk of coronary heart disease, and CHARGE-AF simple score for five-year risk of atrial fibrillation. These new features and capabilities are highlighted through two sample queries in the database. We hope that the broad dissemination of this data will help researchers continue to explore genotype-phenotype correlations and identify novel variants for functional analysis, enabling scientific discoveries in the field of population genomics.Database URL: https://data.color.com/

Introduction The National Blood Collection and Utilization Survey (NBCUS) has demonstrated declines in blood collection and transfusion in the United States since 2008, including declines of 11.6% in red blood cell (RBC) collections and 13.9% in RBC transfusions during 2013-2015. This study described the 2017 NBCUS results. Methods The 2017 NBCUS was distributed to all US blood collection centers, all hospitals performing at least 1000 surgeries annually, and a 40% random sample of hospitals performing 100 to 999 surgeries annually. Weighting and imputation were used to generate national estimates for units of blood and components collected, deferred, distributed, transfused, and outdated. Results Response rates for the 2017 NBCUS were 88% for blood collection centers and 86% for transfusing hospitals. Compared with 2015, the number of RBC units collected during 2017 (12,211,000; 95% confidence interval [CI], 11,680,000-12,742,000) declined by 3.0%, and transfused RBC units (10,654,000, 95% CI, 10,314,000-10,995,000) declined by 6.1%. Distributed platelet (PLT) units (2,560,000; 95% CI, 2,391,000-2,730,000 units) increased by 5.1%, and transfused PLT units (1,937,000, 95% CI, 1,794,000-2,079,000) declined by 2.3%. Distributed plasma units (3,209,000; 95% CI, 2,879,000-3,539,000) declined by 13.6%, and transfused plasma units (2,374,000; 95% CI, 2,262,000-2,487,000) declined by 12.9%. Conclusion The 2017 NBCUS suggests a continued but slowing decline in demand for RBCs. The decline in blood collection and use will likely continue. Despite decreasing demand and increasing manufacturing costs of blood products, the US blood industry has met the regular and emergent needs of the country.

The current value-driven healthcare system encourages physicians to continuously optimize the value of the services they provide. Relative value units (RVUs) serve as the basis of a reimbursement model linking the concept that as the effort and value of services provided to patient's increases, physician reimbursement should increase proportionately. Spine surgery is particularly affected by these factors as there are multiple ways to achieve similar outcomes, some of which require more time, effort, and risk. Specifically, as the trend of spinal interbody fusion has increased over the past decade, the optimal approach to use-posterior versus anterior lumbar interbody fusion (PLIF vs. ALIF)-has been a source of controversy. Due to potential discrepancies in effort, one factor to consider is the correlation between RVUs and the time needed to perform a procedure. Therefore, the purpose of this study was to compare: 1) mean RVUs; 2) mean operative time; and 3) mean RVUs per unit of time between PLIF and ALIF with the utilization of a national surgical database. We also performed an individual surgeon cost benefit analysis for performing PLIF versus ALIF.The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was utilized to identify 6,834 patients who underwent PLIF (CPT code: 22630) and 6,985 patients who underwent ALIF (CPT code: 22558) between 2008 and 2015. The mean operative times (in minutes), mean RVUs, and RVUs per minute were calculated and compared using the Student's t-tests. In addition, the reimbursement amount (in dollars) per minute, case, day, and year for an individual surgeon performing PLIF versus ALIF were also calculated and compared. A p-value of less than 0.05 was used as the threshold for statistical significance.Compared to ALIF cases, PLIF cases had longer mean operative times (203 vs. 212 minutes, p0.001). However, PLIF cases were assigned lower mean RVUs than ALIF cases (22.08 vs. 23.52, p0.001). Furthermore, PLIF had a lower mean RVU/minutes than ALIF cases (0.126 vs. 0.154, p0.001). The reimbursement amounts calculated for PLIF versus ALIF were: $4.52 versus $5.53 per minute, $958.66 versus $1,121.95 per case, and $2,875.98 versus $3,365.86 per day. The annual cost difference was $78,380.92.The data from this study indicates a potentially greater annual compensation of nearly $80,000 for performing ALIF as opposed to PLIF due to a higher "hourly rate" for ALIF as is noted by the significantly greater RVU per minute (0.154 vs. 0.126 RVU/minutes). These results can be used by spine surgeons to design more appropriate compensation effective practices while still providing quality care.

Variant pathogenicity classifiers such as SIFT, PolyPhen-2, CADD, and MetaLR assist in interpretation of the hundreds of rare, missense variants in the typical patient genome by deprioritizing some variants as likely benign. These widely used methods misclassify 26 to 38% of known pathogenic mutations, which could lead to missed diagnoses if the classifiers are trusted as definitive in a clinical setting. We developed M-CAP, a clinical pathogenicity classifier that outperforms existing methods at all thresholds and correctly dismisses 60% of rare, missense variants of uncertain significance in a typical genome at 95% sensitivity.

Fibrotic diseases occur in virtually every tissue of the body and are a major cause of mortality, yet they remain largely untreatable and poorly understood on a mechanistic level. The development of anti-fibrotic agents has been hampered, in part, by the insufficient fibrosis biomimicry provided by traditional in vitro platforms. This review focuses on recent advancements toward creating 3-D platforms that mimic key features of fibrosis, as well as the application of novel imaging and sensor techniques to analyze dynamic extracellular matrix remodeling. Several opportunities are highlighted to apply new tools from the fields of biomaterials, imaging, and systems biology to yield pathophysiologically-relevant in vitro platforms that improve our understanding of fibrosis and may enable identification of potential treatment targets.

BACKGROUND The Department of Health and Human Services National Blood Collection and Utilization Survey (NBCUS) has been conducted biennially since 1997. Data are used to estimate national blood collection and utilization. STUDY DESIGN AND METHODS The 2013 Department of Health and Human Services NBCUS is a cross-sectional survey of all US blood collection centers and hospitals as listed in the 2012 American Hospital Association Annual Survey database that perform at least 100 inpatient surgical procedures annually. The study objective was to estimate, with 95% confidence intervals (CIs), the number of blood and blood components collected and transfused in the United States. RESULTS In 2013, a total of 14,237,000 whole blood and apheresis red blood cell (RBC) units (95% CI, 13,639,000-14,835,000) were collected with 13,395,000 available for transfusion. Of these, 13,180,000 (95% CI, 12,389,000-13,972,000) whole blood and RBC units were transfused. This represented a 4.4% decline in the number of transfused units compared to 2011. Outdated (i.e., expired without being transfused) whole blood and RBC units declined by 17.3%. Apheresis (2,318,000; 95% CI, 2,154,000-2,482,000) and whole blood–derived platelet (PLT; 130,000; 95% CI, 23,000-237,000) distribution declined in 2013. Total PLT transfusions increased in 2013 (2,281,000) in comparison to 2011 (2,169,000). Total plasma units distributed (4,338,000) and transfused (3,624,000) declined. CONCLUSION Both blood collection and utilization have declined, but the gap between collection and utilization is narrowing. As collections decline further and hospitals decrease transfusions and manage products more efficiently, the decline in surplus inventory may be a concern for disaster preparedness or other unexpected utilization needs.

Necrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/TH17 polarization. In murine NEC, pro-inflammatory type 3 NKp46−RORγt+Tbet+ innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46+RORγt+ ILC3 are obliterated. Both species exhibit dysregulation of intestinal TLR repertoires, with TLR4 and TLR8 increased, but TLR5-7 and TLR9-12 reduced. Transgenic IL-37 effectively protects mice from intestinal injury and mortality, whilst exogenous IL-37 is only modestly efficacious. Mechanistically, IL-37 favorably modulates immune homeostasis, TLR repertoires and microbial diversity. Moreover, IL-37 and its receptor IL-1R8 are reduced in human NEC epithelia, and IL-37 is lower in blood monocytes from infants with NEC and/or lower birthweight. Our results on NEC pathomechanisms thus implicate type 3 cytokines, TLRs and IL-37 as potential targets for novel NEC therapies., Necrotizing Enterocolitis (NEC) is an untreatable intestinal disease in infants. Here the authors show that human and experimental mouse NEC is associated with altered toll-like receptor expression in the intestine, enhanced Th17/type 3 polarization in adaptive immune and innate lymphoid cells, dysregulated microbiota, and reduced interleukin-37 signaling.