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Background: Neonatal Intensive Care Units utilize incubators to sustain core temperatures associated with transepidermal water loss. High relative humidity in incubators provides an environment for fungi to grow. In August 2022, mold was identified growing in 11 (85%) Neonatal Intensive Care Unit incubators., Methods: A team assembled to address mold in incubators. The environment was addressed as a possible source of contamination by consulting an environmental specialist. The air handler, ducts, and environment were terminally cleaned. Specimens were collected from the contaminated incubators and the manufacturer reviewed cleaning practices. Experimental trials were conducted using the incubators to replicate mold growth after interventions., Results: The environmental consultant approved when the space could be reoccupied. Incubators introduced to the clean environment did not grow mold. Various fungi or yeast were identified in the contaminated incubators. Opportunities to improve cleaning and replacement of parts were identified by the manufacturer. September 2022 to February 2023, 7 experimental trials were completed after cleaning the incubators. Four (36%) of the 11 contaminated incubators were placed back in use due to no fungal growth. No patient illnesses occurred., Conclusions: The interventions implemented stopped ongoing contamination of incubators and use of previously contaminated incubators., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine changes in health-related quality of life (HRQOL), this 2-year follow-up study reassessed the HRQOL of transgender and gender expansive (TG/GE) young people enrolled in a patient registry at the Gender Wellness Center (GWC) in upstate New York., Methods: Registry patients had to have a gender-affirming care follow-up visit at the GWC within a 2 year window (+6 months) of their baseline survey to complete follow-up. Youth <18 years of age completed the Child Health Questionnaire-Child Form 87 (CHQ-CF87); youth >18 years of age completed the Short Form-36v2 (SF-36v2). We analyzed change from baseline to follow-up for 11 CHQ-CF87 subscales and 8 SF-36v2 subscales. We compared follow-up HRQOL results to U.S. population standards. We abstracted receipt of gender-affirming care from GWC electronic medical records., Results: Among the 173 patients who completed HRQOL assessments at baseline, 108 completed follow-up (62% response rate) from May 2019 to March 2022. The mean age for those completing the CHQ-CF87 was 14.6±2.2 years (range 10-17) and for the SF-36v2 was 19.7±2.3 years (range 18-24). CHQ-CF87 Behavior and Role/Social Physical Functioning subscale scores improved significantly among youth 8-17 years of age from baseline. Follow-up SF-36v2 scores for patients 18-24 years of age did not change significantly. Follow-up HRQOL mental health scores remained statistically significantly lower than U.S. population standards for both age groups., Conclusions: Two year follow-up HRQOL data from TG/GE youth receiving gender-affirming care improved in two domains, but did not change among young adults (>18 years of age). Mental health remains suboptimal compared to national standards., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

External quality assessment programs (EQAP) for molecular haematology generally only assess the analytical phase of laboratory testing or provide limited evaluation of post-analytical components. We incorporated comprehensive post-analytical evaluation into an existing national inter-laboratory sample exchange program for molecular haematology due to the increasing complexity of diagnostic molecular testing and interpretation. We report key findings from four years of longitudinal data using this approach. Eighteen participating laboratories enrolled in an annual reciprocal sample exchange program from 2019-2022, which covered conventional and next-generation sequencing (NGS) assays. Participants submitted results on their laboratory information system-generated reports which then underwent central review. Reports were assessed according to consensus values and relevant national and international reporting standards and guidelines. A total of 680 reports were received. Laboratories had high concordance in the analytical phase of testing, with incorrect variant detection observed in a total of six of 680 (0.9%) reports. In contrast, post-analytical concordance was much lower, with at least one discordance observed in 28.9-57.6% of all conventional reports and 33.3-100% NGS reports. The most frequent post-analytical discordances were: (1) not including key technical information on reports (total 41.9% conventional, 47.2% NGS); (2) not using standard gene and variant nomenclature (total 28.2% conventional, 25.6% NGS). NGS reports also demonstrated discrepancies in variant classification (total 20.4%) and interpretation (total 10.2%). The rate of discrepancies generally improved year-on-year. Inter-laboratory concordance for molecular haematology testing is high in the analytical phase, however opportunities exist for improvement in the post-analytical phase. Given that result interpretation is crucial for clinical decision-making and that molecular testing is a complex and evolving field, we suggest that EQAPs should comprehensively evaluate both analytical and post-analytical components of laboratory performance in order to harmonise reporting and to support the accurate interpretation of molecular haematology tests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Circulating tumor DNA (ctDNA) holds promise as a biomarker for predicting clinical responses to therapy in solid tumors, and multiple ctDNA assays are in development. However, the heterogeneity in ctDNA levels prior to treatment (baseline) across different cancer types and stages and across ctDNA assays has not been widely studied. Friends of Cancer Research formed a collaboration across multiple commercial ctDNA assay developers to assess baseline ctDNA levels across five cancer types in early- and late-stage disease. This retrospective study included eight commercial ctDNA assay developers providing summary-level de-identified data for patients with non-small cell lung cancer (NSCLC), bladder, breast, prostate, and head and neck squamous cell carcinoma following a common analysis protocol. Baseline ctDNA levels across late-stage cancer types were similarly detected, highlighting the potential use of ctDNA as a biomarker in these cancer types. Variability was observed in ctDNA levels across assays in early-stage NSCLC, indicative of the contribution of assay analytical performance and methodology on variability. We identified key data elements, including assay characteristics and clinicopathological metadata, that need to be standardized for future meta-analyses across multiple assays. This work facilitates evidence generation opportunities to support the use of ctDNA as a biomarker for clinical response.

Objective: To describe the prevalence and predictors of postpartum sleep disorders., Design: A retrospective cohort study., Setting: Postpartum., Population: Commercially insured women delivering in California (USA) between 2011 and 2014., Methods: Using the Optum Clinformatics Datamart Database., Main Outcome Measures: Prevalence of a postpartum sleep disorder diagnosis with and without a depression diagnosis up to 12 months following hospital discharge for inpatient delivery. We also identified predictors of a postpartum sleep disorder diagnosis using multivariable logistic regression., Results: We identified 3535 (1.9%) women with a postpartum sleep disorder diagnosis. The prevalence of sleep disorder diagnoses was insomnia (1.3%), sleep apnea (0.25%), and other sleep disorder (0.25%). The odds of a postpartum sleep disorder were highest among women with a history of drug abuse (adjusted odds ratio (aOR): 2.70, 95% confidence interval (CI): 1.79-4.09); a stillbirth delivery (aOR: 2.15, 95% CI: 1.53-3.01); and chronic hypertension (aOR: 1.82; 95% CI: 1.57-2.11). A comorbid diagnosis of a postpartum sleep disorder and depression occurred in 1182 women (0.6%). These women accounted for 33.4% of all women with a postpartum sleep disorder. The strongest predictors of a comorbid diagnosis were a history of drug abuse (aOR: 4.13; 95% CI: 2.37-7.21) and a stillbirth delivery (aOR: 2.93; 95% CI: 1.74-4.92)., Conclusions: Postpartum sleep disorders are underdiagnosed conditions, with only 2% of postpartum women in this cohort receiving a sleep diagnosis using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Insomnia was the most common disorder and one-third of women diagnosed with a postpartum sleep disorder had a co-morbid diagnosis of depression. Future studies are needed to improve the screening and diagnostic accuracy of postpartum sleep disorders.

Fluctuations in planar magnetotransport are ubiquitous in topological HgTe structures, in both tensile (topological insulator) and compressively strained layers (Weyl semimetal phase). We show that the common reason for the fluctuations is the presence of tilted Dirac cones combined with the formation of charge puddles. The origin of the tilted Dirac cones is the mix of the Zeeman term due to the in-plane magnetic field and quadratic contributions to the dispersion relation. We develop a network model that mimics the transport of tilted Dirac fermions in the landscape of charge puddles. The model captures the essential features of the experimental data. It should be relevant for the interpretation of planar magnetotransport in a variety of topological and small band gap materials.

The recent advent of topological states of matter spawned many significant discoveries. The quantum anomalous Hall (QAH) effect is a prime example due to its potential for applications in quantum metrology, as well as its influence on fundamental research into the underlying topological and magnetic states and into axion electrodynamics. Here, electronic transport studies on a (V,Bi,Sb) 2 Te 3 ferromagnetic topological insulator nanostructure in the QAH regime are presented. This allows access to the dynamics of an individual ferromagnetic domain. The domain size is estimated to be in the 50-100 nm range. Telegraph noise resulting from the magnetization fluctuations of this domain is observed in the Hall signal. Careful analysis of the influence of temperature and external magnetic field on the domain switching statistics provides evidence for quantum tunneling (QT) of magnetization in a macrospin state. This ferromagnetic macrospin is not only the largest magnetic object in which QT is observed, but also the first observation of the effect in a topological state of matter., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The vertebrate head skeleton has evolved a myriad of forms since their divergence from invertebrate chordates. The connection between novel gene expression and cell types is therefore of importance in this process. The transformation of the jawed vertebrate (gnathostome) head skeleton from oral cirri to jointed jaw elements required a diversity of cartilages as well as changes in the patterning of these tissues. Although lampreys are a sister clade to gnathostomes, they display skeletal diversity with distinct gene expression and histologies, a useful model for addressing joint evolution. Specifically, the lamprey tissue known as mucocartilage has noted similarities with the jointed elements of the mandibular arch in jawed vertebrates. We thus asked whether the cells in lamprey mucocartilage and gnathostome joint tissue could be considered homologous. To do this, we characterized new genes that are involved in gnathostome joint formation and characterized the histochemical properties of lamprey skeletal types. We find that most of these genes are minimally found in mucocartilage and are likely later innovations, but we do identify new activity for gdf5/6/7b in both hyaline and mucocartilage, supporting its role as a chondrogenic regulator. Contrary to previous works, our histological assays do not find any perichondrial fibroblasts surrounding mucocartilage, suggesting that mucocartilage is non-skeletogenic tissue that is partially chondrified. Interestingly, we also identify new histochemical features of the lamprey otic capsule that diverge from normal hyaline. Paired with our new insights into lamprey mucocartilage, we propose a broader framework for skeletal evolution in which an ancestral soxD/E and gdf5/6/7 network directs mesenchyme along a spectrum of cartilage-like features., (© 2023. The Author(s).)

Purpose: Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression-based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis., Materials and Methods: We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays., Results: In the training cohort, the refined transcriptomic classifier in FFPE tissues showed high sensitivity (> 80%), specificity (> 95%), and accuracy (> 94%) for PTCL subclassification compared with the fresh-frozen-derived diagnostic model and showed high reproducibility between three independent laboratories. In the validation cohort, the transcriptional classifier matched the pathology diagnosis rendered by three expert hematopathologists in 85% (n = 119) of the cases, showed borderline association with the molecular signatures in 6% (n = 8), and disagreed in 8% (n = 11). The classifier improved the pathology diagnosis in two cases, validated by clinical findings. Of the 11 cases with disagreements, four had a molecular classification that may provide an improvement over pathology diagnosis on the basis of overall transcriptomic and morphological features. The molecular subclassification provided a comprehensive molecular characterization of PTCL subtypes, including viral etiologic factors and translocation partners., Conclusion: We developed a novel transcriptomic approach for PTCL subclassification that facilitates translation into clinical practice with higher precision and uniformity than conventional pathology diagnosis.

Alpha-1 antitrypsin (AAT) deficiency (AATD) is an inherited disease caused by mutations in the serpin family A member 1 (SERPINA1, also known as AAT) gene. The most common variant, PI*Z (Glu342Lys), causes accumulation of aberrantly folded AAT in the endoplasmic reticulum (ER) of hepatocytes that is associated with a toxic gain of function, hepatocellular injury, liver fibrosis, and hepatocellular carcinoma. The unfolded protein response (UPR) is a cellular response to improperly folded proteins meant to alleviate ER stress. It has been unclear whether PI*Z AAT elicits liver cell UPR, due in part to limitations of current cellular and animal models. This study investigates whether UPR is activated in a novel human PI*Z AAT cell line and a new PI*Z human AAT (hAAT) mouse model. A PI*Z AAT hepatocyte cell line (Huh7.5Z) was established using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing of the normal ATT (PI*MM) gene in the Huh7.5 cell line. Additionally, novel full-length genomic DNA PI*Z hAAT and PI*M hAAT transgenic mouse models were established. Using these new models, UPR in Huh7.5Z cells and PI*Z mice were comprehensively determined. Robust activation of UPR was observed in Huh7.5Z cells compared to Huh7.5 cells. Activated caspase cascade and apoptosis markers, increased chaperones, and autophagy markers were also detected in Z hepatocytes. Selective attenuation of UPR signaling branches was observed in PI*Z hAAT mice in which the protein kinase R-like ER kinase and inositol-requiring enzyme1α branches were suppressed while the activating transcription factor 6α branch remained active. This study provides direct evidence that PI*Z AAT triggers canonical UPR and that hepatocytes survive pro-apoptotic UPR by selective suppression of UPR branches. Our data improve understanding of underlying pathological molecular mechanisms of PI*Z AATD liver disease., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Study Objectives: Poor sleep impedes children's cognitive, emotional, and psychosocial development. Pediatric sleep dysregulation is common, and children who live in communities of low socioeconomic status experience additional risk factors for short sleep duration and poor sleep quality. School-based training in mindfulness and yoga-informed practices can improve children's behavior and well-being, but effects on objectively measured sleep are unknown., Methods: Effects of a school-based health and mindfulness curriculum, which taught practices such as paced breathing, on sleep and stress were examined in 115 children (49 girls, ages 8 to 11 at baseline). Fifty-eight children in a community of low socioeconomic status received the curriculum twice weekly for 2 years. Fifty-seven children in a socioeconomic status-matched community engaged in their usual physical education class instead. In-home ambulatory polysomnography and perceived social stress were measured in all children at 3 time points: at baseline (ie, prior to curriculum exposure) and at 2 yearly follow-ups., Results: Children receiving the curriculum gained an average of 74 minutes of total sleep time, and 24 minutes of rapid eye movement sleep, per night over the 2-year study period. Children not receiving the curriculum experienced a decrease in total sleep time averaging 64 minutes per night, with no changes in rapid eye movement sleep. Sleep improved within the first 3 months of curriculum exposure, in a dose-dependent fashion. Higher curriculum engagement (eg, using the breathing exercises outside of class) was associated with larger gains in total and rapid eye movement sleep duration. Aggregate within-group changes in social stress were not significant. However, among children receiving the curriculum, those who experienced larger gains in total and rapid eye movement sleep duration also experienced larger increases in perceived social stress., Conclusions: A school-based health and mindfulness curriculum improved children's objectively measured sleep over 2 years. Social stress did not mediate these effects; instead, mindfulness training may have increased awareness of environmental stressors, while developing tools to reduce stress vulnerability., Citation: Chick CF, Singh A, Anker LA, et al. A school-based health and mindfulness curriculum improves children's objectively measured sleep: a prospective observational cohort study. J Clin Sleep Med . 2022;18(9):2261-2271., (© 2022 American Academy of Sleep Medicine.)

Introduction: Cystic fibrosis (CF) is the most common life-threatening genetic illness in the United States. People with CF as well as their caregivers are up to three times more likely to report experiencing symptoms of depression and anxiety than those without CF. In 2016, the Cystic Fibrosis Foundation and the European Cystic Fibrosis Society came together to form the International Committee on Mental Health in CF and released guidelines outlining behavioral health (BH) screening recommendations for patients with CF and at least one primary caregiver. This study sought to characterize the role of BH care in routine CF treatment within the DoD health care system and identify potential opportunities for improvement. The resultant brief report is intended to elucidate and present identified areas of improvement as well as to inform further research projects in this field., Materials and Methods: A representative sample of program leaders (8 of 12; five program directors and three nurse coordinators) from all six affiliate CF centers in the DoD completed a 23-item web-based survey. This study sought to identify the following: (1) What tools are DoD affiliate CF centers using to screen patients with CF and their caregiver(s) for psychological distress and how often does screening take place? (2) What is the composition of the DoD's CF BH teams by specialty and to what degree are BH personnel available to support the needs of CF patients? (3) How comfortable are program directors and nurse coordinators in screening patients with CF and their caregiver(s) for indicators of psychological distress? (4) How familiar are CF BH teams with the use of the U.S. Military's Behavioral Health Data Portal (BHDP)? This descriptive study was approved by the Human Use Committee at the Tripler Army Medical Center., Results: The results of this study indicated that 80% of the DoD affiliate CF centers are screening patients with CF who are 12 years and older and at least one caregiver at least annually for depression and anxiety with the Patient Health Questionnaire depression module and generalized anxiety disorder screening tool, respectively. Reported screening tools for suicidality were not standardized across centers. All respondents indicated that there is a designated social worker in their CF clinic team. Three-quarters of respondents reported that their social worker is physically present in CF clinics 75%-100% of the time. Other types of BH team members varied by clinic. Program directors and nurse coordinators on average indicated feeling "somewhat comfortable" in screening patients with CF for depression, anxiety, and suicidality. Eighty percent of program directors reported being "not so comfortable" in screening caregivers for depression, anxiety, and suicidality, with nurse coordinators on average reporting feeling "somewhat comfortable." Eighty percent of affiliate CF centers indicated that they are unaware of, are not utilizing, or do not have access to the BHDP to screen and record BH data for patients with CF or their caregiver(s)., Conclusions: This study characterized routine CF BH care at DoD affiliate CF centers. Areas for improvement include the standardized use of screening tools for suicidality, increased provider comfort with screening, and streamlined recording and tracking of this data using the BHDP. Limitations of this study include inherent self-report bias, specifically social desirability bias. Steps toward suggested improvements and further utilization of the BHDP may improve BH care for patients with CF and their caregiver(s) in addition to facilitating future research., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Hybrid samples combining superconductors with magnetic topological insulators are a promising platform for exploring exotic new transport physics. We examine a Josephson junction of such a system based on the dilute magnetic topological insulator (Hg,Mn)Te and the type II superconductor MoRe. In the zero and very low field limits, to the best of our knowledge, the device shows, for the first time, an induced supercurrent through a magnetically doped semiconductor, in this case, a topological insulator. At higher fields, a rich and hysteretic magnetoresistance is revealed. Careful analysis shows that the explanation of this behavior can be found in magnetic flux focusing stemming from the Meissner effect in the superconductor, without invoking any role of proximity-induced superconductivity. The phenomena is important because it will ubiquitously coexist with any exotic new physics that may be present in this class of devices.

Background: Despite the increasing availability of telemedicine video visits during the COVID-19 pandemic, older adults have greater challenges in getting care through telemedicine., Objective: We aim to better understand the barriers to telemedicine in community-dwelling older adults to improve the access to and experience of virtual visits., Methods: We conducted a mixed methods needs assessment of older adults at two independent living facilities (sites A and B) in Northern California between September 2020 and March 2021. Voluntary surveys were distributed. Semistructured interviews were then conducted with participants who provided contact information. Surveys ascertained participants' preferred devices as well as comfort level, support, and top barriers regarding telephonic and video visits. Qualitative analysis of transcribed interviews identified key themes., Results: Survey respondents' (N=249) average age was 84.6 (SD 6.6) years, and 76.7% (n=191) of the participants were female. At site A, 88.9% (111/125) had a bachelor's degree or beyond, and 99.2% (124/125) listed English as their preferred language. At site B, 42.9% (51/119) had a bachelor's degree or beyond, and 13.4% (16/119) preferred English, while 73.1% (87/119) preferred Mandarin. Regarding video visits, 36.5% (91/249) of all participants felt comfortable connecting with their health care team through video visits. Regarding top barriers, participants at site A reported not knowing how to connect to the platform (30/125, 24%), not being familiar with the technology (28/125, 22.4%), and having difficulty hearing (19/125, 15.2%), whereas for site B, the top barriers were not being able to speak English well (65/119, 54.6%), lack of familiarity with technology and the internet (44/119, 36.9%), and lack of interest in seeing providers outside of the clinic (42/119, 35.3%). Three key themes emerged from the follow-up interviews (n=15): (1) the perceived limitations of video visits, (2) the overwhelming process of learning the technology for telemedicine, and (3) the desire for in-person or on-demand help with telemedicine., Conclusions: Substantial barriers exist for older adults in connecting with their health care team through telemedicine, particularly through video visits. The largest barriers include difficulty with technology or using the video visit platform, hearing difficulty, language barriers, and lack of desire to see providers virtually. Efforts to improve telemedicine access for older adults should take into account patient perspectives., (©Alice Mao, Lydia Tam, Audrey Xu, Kim Osborn, Meera Sheffrin, Christine Gould, Erika Schillinger, Marina Martin, Matthew Mesias. Originally published in JMIR Aging (https://aging.jmir.org), 19.04.2022.)

Objective: The study aimed to evaluate the effect of the aerodigestive clinic (ADC) on healthcare utilization., Study Design: Retrospective quality improvement project; before and after., Setting: The ADC at Tripler Army Medical Center (TAMC) in Honolulu, HI., Methods: We retrospectively analyzed the electronic medical records of children ≤17 years old seen in the ADC at TAMC between April 2015 and June 2019. The number of emergency department (ED), primary care (PC), specialty care (SC), ancillary care (AC), and teleconsult (TC) encounters were tallied before and after one year of the initial intake visit., Results: A total of 261 children were included during the study period. Comparing visits before aerodigestive evaluation to after aerodigestive evaluation, the total number of visits before and after were similar with significant changes in the distribution of encounters. The total number of ED (-38%) and PC (-40%) visits decreased significantly (p < 0.001 for both). The total number of other visits were found to have non-significant increases. PC visits accounted for nearly one-third (31%) of all visits prior to the initial ADC visit, but only 19% of visits after. PC visits decreased for all age groups. ED visits decreased by nearly half (-48.1%) for ages 1-17, but there was no change for <1-year olds., Conclusion: There is a statistically significant reduction in the number of emergency department and primary care visits for patients seen in a multidisciplinary ADC. The distribution of visits differed strongly among age groups. These findings emphasize the positive impact that the multidisciplinary clinic has on healthcare utilization for pediatric aerodigestive patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Vertebrates have distinct tissues which are not present in invertebrate chordates nor other metazoans. The rise of these tissues also coincided with at least one round of whole-genome duplication as well as a suite of lineage-specific segmental duplications. Understanding whether novel genes lead to the origin and diversification of novel cell types, therefore, is of great importance in vertebrate evolution. Here we were particularly interested in the evolution of the vertebrate musculoskeletal system, the muscles and connective tissues that support a diversity of body plans. A major component of the musculoskeletal extracellular matrix (ECM) is fibrillar collagens, a gene family which has been greatly expanded upon in vertebrates. We thus asked whether the repertoire of fibrillar collagens in vertebrates reflects differences in the musculoskeletal system. To test this, we explored the diversity of fibrillar collagens in lamprey, a jawless vertebrate which diverged from jawed vertebrates (gnathostomes) more than five hundred million years ago and has undergone its own gene duplications. Some of the principal components of vertebrate hyaline cartilage are the fibrillar collagens type II and XI, but their presence in cartilage development across all vertebrate taxa has been disputed. We particularly emphasized the characterization of genes in the lamprey hyaline cartilage, testing if its collagen repertoire was similar to that in gnathostomes. Overall, we discovered thirteen fibrillar collagens from all known gene subfamilies in lamprey and were able to identify several lineage-specific duplications. We found that, while the collagen loci have undergone rearrangement, the Clade A genes have remained linked with the hox clusters, a phenomenon also seen in gnathostomes. While the lamprey muscular tissue was largely similar to that seen in gnathostomes, we saw considerable differences in the larval lamprey skeletal tissue, with distinct collagen combinations pertaining to different cartilage types. Our gene expression analyses were unable to identify type II collagen in the sea lamprey hyaline cartilage nor any other fibrillar collagen during chondrogenesis at the stages observed, meaning that sea lamprey likely no longer require these genes during early cartilage development. Our findings suggest that fibrillar collagens were multifunctional across the musculoskeletal system in the last common ancestor of vertebrates and have been largely conserved, but these genes alone cannot explain the origin of novel cell types., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Root, Allen, Gould, Brewer, Jandzik and Medeiros.)

There is a wealth of literature investigating the role of family involvement within care homes following placement of a relative with dementia. This review summarises how family involvement is measured and aims to address two questions: (1) which interventions concerning family involvement have been evaluated? And (2) does family involvement within care homes have a positive effect on a resident's quality of life and behavioural and psychological symptoms of dementia? After searching and screening on the three major databases PsycINFO, MEDLINE and CINAHL Plus for papers published between January 2005 and May 2021, 22 papers were included for synthesis and appraisal due to their relevance to family involvement interventions and or family involvement with resident outcomes. Results show that in 11 interventions designed to enhance at least one type of family involvement, most found positive changes in communication and family-staff relationships. Improvement in resident behavioural and psychological symptoms of dementia was reported in two randomised controlled trials promoting partnership. Visit frequency was associated with a reduction of behavioural and psychological symptoms of dementia for residents with moderate dementia. Family involvement was related to positive quality of life benefits for residents. Contrasting results and methodological weaknesses in some studies made definitive conclusions difficult. Few interventions to specifically promote family involvement within care homes following placement of a relative with dementia have been evaluated. Many proposals for further research made over a decade ago by Gaugler (2005) have yet to be extensively pursued. Uncertainty remains about how best to facilitate an optimum level and type of family involvement to ensure significant quality of life and behavioural and psychological symptoms of dementia benefits for residents with dementia.

Purpose: While lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) elders face a multitude of barriers to healthy aging, little is known about needs and concerns specific to transgender elders, except that they face many self-perceived challenges to healthy aging, which exist at the individual, community, and institutional levels. To further understand these needs, we explored the perspectives of transgender individuals aged 65 and older on health care, expectations of aging, concerns for the future, and advice for young transgender people. Methods: We performed 19 semistructured interviews with individuals who identify as transgender elders, 10 transgender women and 9 transgender men. Interviews were transcribed and coded by three investigators to generate salient themes via thematic analysis. Results: We identified 7 major themes that exemplify the concerns and experiences of this sample of the aging transgender community: fear of mistreatment in elder care, isolation and loneliness exacerbated by transgender identity, increased vulnerability to financial stressors, perceived lack of agency, health care system and provider inclusivity, giving back to one's community, and embracing self-truth as a path to fulfillment. Conclusion: While some of these concerns, such as fear of mistreatment, are common among elders, the concerns of transgender elders are heightened due to stigma compounded by being both transgender and elderly. Health care providers, nursing home staff, and social workers must be sensitized to these needs and fears to provide appropriate, affirming, and respectful care and support to transgender elders., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

Research has found that occupational therapy practitioners focus on functional and participation outcomes in the low vision population, but overlook corresponding psychosocial outcomes in rehabilitation. The purpose of this systematic review is to answer the PICO question: "What is the evidence to support interventions within the scope of occupational therapy for improving psychosocial well-being or quality of life in adults experiencing depression or anxiety as a result of low vision?" The team conducted a search of literature published between 2008 and 2020. Inclusion criteria consisted of interventions within the scope of occupational therapy for patients with low vision, and which measured mental health or quality of life factors. Eleven articles met inclusion criteria. The majority of the evidence consisted of 1B (45%) and 2B (36%) level randomized control trials. Two studies were 3B level evidence. Mental health outcomes were measured primarily using depression rating scales, although a number of studies also utilized vision-specific quality of life questionnaires. Established intervention themes included behavioral activation plus occupational therapy low vision rehabilitation, cognitive problem-solving approaches, usual care 'plus' skill-based training, and group service delivery approaches. Moderate evidence supports behavioral activation plus occupational therapy low vision rehabilitation, problem-solving approaches, and group service delivery approaches for improving mental health outcomes. There is moderate evidence that does not support usual treatment 'plus' skill-based training to improve mental health.

Richter syndrome (RS), an aggressive lymphoma occurring in the context of chronic lymphocytic leukaemia/small lymphocytic lymphoma, is associated with poor prognosis when treated with conventional immunochemotherapy, therefore, improved treatments are required. Immune checkpoint blockade has shown efficacy in some B-cell malignancies and modest responses in early clinical trials for RS. We investigated the immune checkpoint profile of RS as a basis to inform rational therapeutic investigations in RS. Formalin-fixed, paraffin-embedded biopsies of RS (n = 19), de novo diffuse large B-cell lymphoma (DLBCL; n = 58), transformed indolent lymphomas (follicular [tFL], n = 16; marginal zone [tMZL], n = 24) and non-transformed small lymphocytic lymphoma (SLL; n = 15) underwent gene expression profiling using the NanoString Human Immunology panel. Copy number assessment was performed using next-generation sequencing. Immunohistochemistry (IHC) for LAG3 and PD-1 was performed. LAG3 gene expression was higher in RS compared to DLBCL (P = 0·0002, log2FC 1·96), tFL (P < 0·0001, log2FC 2·61), tMZL (P = 0·0004, log2FC 1·79) and SLL (P = 0·0057, log2FC 1·45). LAG3 gene expression correlated with the gene expression of human leukocyte antigen Class I and II, and related immune genes and immune checkpoints. IHC revealed LAG3 protein expression on both malignant RS cells and tumour-infiltrating lymphocytes. Our findings support the investigation of LAG3 inhibition to enhance anti-tumour responses in RS., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Achieving metrological precision of quantum anomalous Hall resistance quantization at zero magnetic field so far remains limited to temperatures of the order of 20 mK, while the Curie temperature in the involved material is as high as 20 K. The reason for this discrepancy remains one of the biggest open questions surrounding the effect, and is the focus of this article. Here we show, through a careful analysis of the non-local voltages on a multi-terminal Corbino geometry, that the chiral edge channels continue to exist without applied magnetic field up to the Curie temperature of bulk ferromagnetism of the magnetic topological insulator, and that thermally activated bulk conductance is responsible for this quantization breakdown. Our results offer important insights on the nature of the topological protection of these edge channels, provide an encouraging sign for potential applications, and establish the multi-terminal Corbino geometry as a powerful tool for the study of edge channel transport in topological materials., (© 2021. The Author(s).)

Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression (eg, posttransplant lymphoproliferative disorders or HIV [AIDS-related PCNSL]). These cases are poorly characterized, have dismal outcome, and are typically Epstein-Barr virus (EBV)-associated (ie, tissue-positive). We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. Forty-seven were EBV tissue-negative: 45 EBV- HIV- PCNSL and 2 EBV- HIV+ PCNSL; and 44 were EBV tissue-positive: 23 EBV+ HIV+ PCNSL and 21 EBV+ HIV- PCNSL. As with prior studies, EBV- HIV- PCNSL had frequent MYD88, CD79B, and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin subtype. In contrast, these mutations were absent in all EBV tissue-positive cases and ABC frequency was low. Furthermore, copy number loss in HLA class I/II and antigen-presenting/processing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV+ HIV- PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-associated PCNSL in the immunosuppressed is immunobiologically distinct from EBV- HIV- PCNSL, and, despite expressing an immunogenic virus, retains the ability to present EBV antigens. Results provide a framework for targeted treatment., (© 2021 by The American Society of Hematology.)

Purpose: Transgender and gender-expansive (TGE) populations are at increased risk for nonsuicidal self-injury (NSSI). Rural TGE populations are understudied and underserved in terms of mental health services. The purpose of this study was to determine lifetime prevalence of NSSI among TGE youth at a rural gender wellness clinic and identify demographic and clinical characteristics associated with NSSI. Methods: The Gender Wellness Center Pediatric Patient Registry, a comprehensive database of 185 TGE youth ≤25 years of age, provided an estimate of the lifetime prevalence of NSSI. Univariate logistic regression models were utilized to test associations between patient demographic and clinical characteristics and NSSI. Variables that met the threshold for significance in the univariate analyses ( p <0.05) were entered into a multivariate logistic regression model. All statistical analyses were conducted in SAS v.9.4. Results: Prevalence of NSSI in the sample was 36.8% ( n =68). In unadjusted logistic regression models, risk factors for NSSI included female assigned sex at birth, transmasculine spectrum gender identity, history of mood disorder, history of suicidal ideation (SI) or attempt, and history of abuse ( p <0.05). In the adjusted model, variables significantly associated with NSSI included female assigned sex at birth, history of mood disorder, and history of SI or attempt. Conclusion: NSSI was highly prevalent in this sample of rural TGE youth, confirming the need for screening and early interventions that target the unique vulnerabilities of TGE youth. The complex interplay of sex assigned at birth, mood disorders, and NSSI requires further research., Competing Interests: The authors have no conflict of interest, real or perceived, to disclose., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

Background: To characterize the experience of converting a geriatrics clinic to telehealth visits in early stages of a pandemic., Design: An organizational case study with mixed methods evaluation from the first 8 weeks of converting a geriatrics clinic from in-person visits to video and telephone visits., Setting: Veteran's Health Administration in Northern California Participants Community-dwelling older Veterans receiving care at VA Palo Alto Geriatrics clinic. Veterans had a mean age of 85.7 (SD = 6.8) and 72.1% had cognitive impairment., Intervention: Veterans with face-to-face appointments were converted to video or telephone visits to mitigate exposure to community spread of COVID-19., Measurements: Thirty-two patient evaluations and 80 clinician feedback evaluations were completed. This provided information on satisfaction, care access during pandemic, and travel and time savings., Results: Of the 62 scheduled appointments, 43 virtual visits (69.4%) were conducted. Twenty-six (60.5%) visits were conducted via video, 17 (39.5%) by telephone. Virtual visits saved patients an average of 118.6 minutes each. Patients and providers had similar, positive perceptions about telehealth to in-person visit comparison, limiting exposure, and visit satisfaction. After the telehealth appointment, patients indicated greater comfort with using virtual visits in the future. Thirty-one evaluations included comments for qualitative analysis. We identified 3 main themes of technology set-up and usability, satisfaction with visit, and clinical assessment and communication., Conclusion: During a pandemic that has limited the ability to safely conduct inperson services, virtual formats offer a feasible and acceptable alternative for clinically-complex older patients. Despite potential barriers and additional effort required for telehealth visits, patients expressed willingness to utilize this format. Patients and providers reported high satisfaction, particularly with the ability to access care similar to in-person while staying safe. Investing in telehealth services during a pandemic ensures that vulnerable older patients can access care while maintaining social distancing, an important safety measure.

Background: Transgender people face numerous barriers to accessing care, particularly in rural settings. Transportation, travel time, a lack of providers offering transgender care, and discrimination all contribute to these barriers. The Gender Wellness Center was established in New York State, USA, to fill a gap in rural transgender care and was subsequently awarded a Robert Wood Johnson Foundation grant to establish a Center of Excellence. This study examined the implementation of the Center of Excellence, a complex intervention, to assess barriers and facilitators to implementation over 18 months., Methods: The Consolidated Framework for Implementation Research (CFIR) was used to develop baseline and follow-up surveys. These were distributed to members of the core implementation team at the Gender Wellness Center at the midpoint and conclusion of the Robert Wood Johnson Foundation grant. Responses were largely open-ended and analyzed qualitatively., Results: Results are presented in terms of CFIR domains and constructs, as well as the relative outlook (positive or negative) of implementation. Overall, there were improvements over time, with more encouraging feedback and examples of success at follow-up. Though true, organizational culture and individual beliefs about the provision of transgender care challenged implementation of the Center of Excellence throughout the project., Conclusions: This study highlights the importance of organizational culture on implementation efforts, as well as the need for complex, multifaceted interventions to overcome such challenges in order to improve care for marginalized populations.

Efforts to reduce the health and ecological burdens of household biomass combustion are underway in Ghana, principally by promoting clean cookstoves and fuels. Recent studies have focused on the sustained use of clean cookstoves, but sometimes household adopt a new cookstove and then end use of that stove. In this study, we introduce a novel framework for understanding and encouraging household transitions to cleaner cooking: clean fuel discontinuance. We leveraged data from the Ghana Randomized Air Pollution and Health Study (GRAPHS) (N = 1412) where pregnant women received either improved biomass (BioLite) or dual burner LPG stoves for free. LPG users were given free LPG refills during GRAPHS. Weekly questionnaires were administered. Stove use monitors tracked a sub-cohort (n = 220) 6 months before and after the fuel subsidy. We examined social and ecological determinants of stove use and discontinuance. Overall intervention stove use adherence was high throughout GRAPHS, with self-reported use at 69% and 86% of participant-weeks for BioLite and LPG arms respectively. Participants used intervention stoves less for meals requiring vigorous stirring. Burns from intervention stoves decreased use among BioLite (RR: 0.96, p = 0.009), but not LPG users. Device breakage was mentioned as an impediment in 18% of free-text responses for LPG users and 1% for BioLite. Tree canopy within a spatial buffer-a plausible proxy for biomass fuels access-was the only variable explaining LPG discontinued stove use in adjusted Cox time-to-event analyses (HR = -0.56, p < 0.001). Future studies should consider the stove use discontinuance framework.

Fatty falciform ligament appendage torsion (F-FLAT) is a rare type of intraperitoneal focal fat infarction that involves torsion of a fatty appendage of the falciform ligament. It may cause severe pain, mimicking an acute abdomen, but is typically self-limited and does not require hospitalisation or surgery. As a type of intraperitoneal focal fat infarction, it shares many of the same physiological, clinical and radiological features of epiploic appendagitis. To our knowledge, F-FLAT has not previously been reported in a patient following a laparoscopic Roux-en-Y gastric bypass surgery. Identifying falciform ligament appendagitis is critical because it can prevent unnecessary hospitalisation, follow-up studies and surgery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To address a critical gap in the existing Health-Related Quality of Life (HRQOL) literature by quantifying and describing HRQOL among transgender and gender expansive (TG/GE) youth at a rural gender clinic and comparing the HRQOL of these youth to age-stratified United States (U.S.) population standards., Methods: This cross-sectional study includes results of the baseline HRQOL assessment of 141 TG/GE patients enrolled in the Gender Wellness Center (GWC) Pediatric Patient Registry. HRQOL was assessed using the Child Health Questionnaire-Child Form 87 (CHQ-CF87; ages < 18) and the Short Form-36 (SF-36v2; ages 18-21). Mean subscale scores were compared to the most current U.S. population standards available., Results: On all but one of the CHQ-CF87 subscales, TG/GE youth scored significantly lower than 2015-2016 U.S. general population youth and youth with two chronic conditions. On the SF-36v2, TG/GE youth scored significantly higher than 2009 U.S. standards on all physical health domains but lower on all but one of the mental health domains., Conclusions: Cross-sectional HRQOL data from a registry of TG/GE youth indicate significantly poorer mental health measures as compared with the U.S. general population. Longitudinal assessments are needed to evaluate whether HRQOL improves with gender-affirming care. Future studies should aim to identify sociocultural factors at the intersection of rurality and health that contribute to diminished HRQOL among rural TG/GE youth.

Background: Self-harm is common in prisoners. There is an association between self-harm in prisoners and subsequent suicide, both within prison and on release. The aim of this study is to develop and evaluate a prediction model to identify male prisoners at high risk of self-harm., Methods: We developed an 11-item screening model, based on risk factors identified from the literature. This screen was administered to 542 prisoners within 7 days of arrival in two male prisons in England. Participants were followed up for 6 months to identify those who subsequently self-harmed in prison. Analysis was conducted using Cox proportional hazard regression. Discrimination and calibration were determined for the model. The model was subsequently optimized using multivariable analysis, weighting variables, and dropping poorly performing items., Results: Seventeen (3.1%) of the participants self-harmed during follow up (median 53 days). The strongest risk factors were previous self-harm in prison (adjusted hazard ratio [aHR] = 9.3 [95% CI: 3.3-16.6]) and current suicidal ideation (aHR = 7.6 [2.1-27.4]). As a continuous score, a one-point increase in the suicide screen was significantly associated with self-harm (HR = 1.4, 1.1-1.7). At the prespecified cut off score of 5, the screening model was associated with an area under the curve (AUC) of 0.66 (0.53-0.79), with poor calibration. The optimized model saw two items dropped from the original screening tool, weighting of risk factors based on a multivariable model, and an AUC of 0.84 (0.76-0.92)., Conclusions: Further work is necessary to clarify the association between risk factors and self-harm in prison. Despite good face validity, current screening tools for self-harm need validation in new prison samples.

Blockade of the PD-1 axis has modest efficacy in diffuse large B-cell lymphoma (DLBCL), but data regarding LAG3 are sparse. The impact of LAG3 digital gene expression was tested in 309 patients with DLBCL treated with standard chemoimmunotherapy. Cellular distribution of LAG3 protein was determined by immunohistochemistry and flow cytometry. In tumor-infiltrating lymphocytes (TILs), LAG3 expression was highest on CD4+ regulatory T cells (Tregs) and was also highly expressed on CD8+ T cells compared with CD4+ non-Tregs (both P = .008). LAG3high TILs were enriched in PD-1 and TIM-3. LAG3 was also expressed on a proportion of malignant B cells, and these patients had significantly higher LAG3 messenger RNA in their biopsies (P = .03). LAG3high gene expression was associated with inferior survival in discovery/validation cohorts, independent of cell of origin and the international prognostic index. Patients who were PD-L1high were fivefold more likely to be LAG3high (P < .0001). Patients who were LAG3high/PD-L1high had an inferior progression-free survival (P = .011) and overall survival (P = .005) compared with patients who were LAG3low/PD-L1high. Digital spatial protein analysis confirms LAG3 expression on T cells and, surprisingly, tumor-associated macrophages (TAMs) at higher levels than found on CD20+ B cells in the tumor microenvironment. LAG3 is frequently expressed on CD4+ Tregs and CD8+ TILs, typically with other immune checkpoints, and is also present in a proportion of malignant B cells in DLBCL and in areas enriched for TAMs. LAG3high expression is associated with poor outcome independent of conventional prognosticators., (© 2020 by The American Society of Hematology.)

A quantum anomalous Hall (QAH) insulator coupled to an s-wave superconductor is predicted to harbor chiral Majorana modes. A recent experiment interprets the half-quantized two-terminal conductance plateau as evidence for these modes in a millimeter-size QAH-niobium hybrid device. However, non-Majorana mechanisms can also generate similar signatures, especially in disordered samples. Here, we studied similar hybrid devices with a well-controlled and transparent interface between the superconductor and the QAH insulator. When the devices are in the QAH state with well-aligned magnetization, the two-terminal conductance is always half-quantized. Our experiment provides a comprehensive understanding of the superconducting proximity effect observed in QAH-superconductor hybrid devices and shows that the half-quantized conductance plateau is unlikely to be induced by chiral Majorana fermions in samples with a highly transparent interface., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objectives: Suicide is a global public health problem among older adults. Problem-solving therapy (PST) has demonstrated promise in reducing late-life suicide risk, chiefly in secondary analyses of studies on late-life depression. PST mitigates negative beliefs about one's problem-solving abilities and maladaptive problem-solving styles, which suicidal older adults report. The effects of PST on suicide risk in older adults with primary anxiety disorder diagnoses have not been examined. Anxiety is a risk factor for suicide, but it is less studied in research on suicide compared to depression. This paper describes two cases of older individuals with anxiety disorders and suicidal ideation who completed six sessions of PST. Methods: Assessments of suicide risk, anxiety, depressive symptoms, and problem-solving ability were administered. Results: Both cases exhibited a clinically significant reduction in suicide risk, along with reductions in anxiety, worry, and depressive symptoms by posttreatment. Conclusions & Clinical Implications: Findings highlight the potential for PST as a psychotherapeutic intervention for reducing suicide risk in older adults with anxiety disorders.

Objective: Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV -pos DLBCL) is a recently identified entity. Data regarding outcome to frontline immuno-chemotherapy are conflicting. Although the prognostic impact of the tumour microenvironment (TME) in EBV -neg DLBCL is well-established, it remains untested whether the TME influences survival in EBV -pos DLBCL. There are no data with new digital gene expression technologies that simultaneously interrogate the virus, B cells and the tumour microenvironment (TME)., Methods: We used the NanoString™ platform in a population-based cohort of 433 patients to establish if the technology could detect EBV in the tumour biopsies and to investigate the influence that EBV has on the complex tumour microenvironment of DLBCL., Results: Incidence of EBV -pos DLBCL was 6.9% with 5-year survival of 65% vs 82% in EBV -neg DLBCL (P = 0.018). EBV -pos tissues had similar expression of T-cell genes compared to EBV -neg DLBCL but higher levels of the antigen-presenting molecule B2M. This was countered by elevated PD-L1, PD-L2, LAG3 and TIM3 immune checkpoints and a higher CD163/CD68 "M2" macrophage score., Conclusion: In EBV -pos DLBCL, the TME is immuno-tolerogenic and may explain the poor outcomes seen in this subtype of DLBCL., (© 2019 The Authors European Journal of Haematology Published by John Wiley & Sons Ltd.)

In advanced-stage diffuse large B-cell lymphoma (DLBCL), the presence of an activated B-cell phenotype or a non-germinal center (GCB) phenotype, coexpression of MYC and BCL2 by immunohistochemistry, and the cooccurrence of MYC and BCL2 or BCL6 rearrangements are associated with inferior outcomes. It is unclear whether these variables remain prognostic in stage I/II patients. In this retrospective study, we evaluated the prognostic impact of cell of origin (COO), as well as dual-expressor (DE) status and molecular double-hit (DH) status, in stage I/II DLBCL by positron emission tomography with computed tomography (PET-CT). A total of 211 patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens, with or without radiotherapy, was included. The median follow-up in the entire cohort was 4 years (range, 0.4-9.4), with estimated 4-year progression-free survival (PFS) and overall survival (OS) rates of 85% (95% confidence interval [CI], 79-89) and 88% (95% CI, 83-92), respectively. By univariable analysis, DE (PFS: hazard ratio [HR], 1.27; 95% CI, 0.58-2.81, P = .55 and OS: HR, 1.40; 95% CI, 0.60-3.30; P = .44), DH (PFS: HR, 1.21; 95% CI, 0.27-5.31; P = .80 and OS: HR, 0.61; 95% CI, 0.08-4.73; P = .64), and non-GCB status (PFS: HR, 1.59; 95% CI, 0.83-3.03; P = .16 and OS: HR, 1.80; 95% CI, 0.89-3.67; P = .10) were associated with poorer outcomes. In patients with PET-CT-defined stage I/II DLBCL treated with R-CHOP-like therapy, with or without radiation, COO and DE and DH status were not significantly associated with inferior PFS or OS., (© 2019 by The American Society of Hematology.)

Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Purpose: Significant knowledge gaps regarding outcomes of gender-affirming therapy in transgender (TG) and gender expansive (GE) youth impede an evidence-based approach to these patients. The Gender Wellness Center (GWC) Pediatric Patient Registry was established in 2017 to enable systematic, longitudinal research to describe the physical, mental, and quality-of-life outcomes of these youth. Methods: All TG/GE youth, ages 8-21 years, presenting to the GWC were recruited on site. Ten research questions guided the creation of data fields. The following 131 variables were abstracted from electronic medical records: demographics, weight, height, body mass index, gender identity, sexual orientation, coexisting diagnoses, substance use, Tanner stage, sexual activity, medications, fertility preservation, Gonadotropin Releasing Hormone (GnRH) analog use, hormone therapy, surgery, and related outcomes. Health-related quality of life is assessed using the Child Health Questionnaire-87 for ages <18 and the Short Form-36 for ages 18-21. Results: To date, 139 TG and GE youth (90% white and 93% non-Hispanic), have enrolled in the registry. Average age at enrollment was 17.5 years (±3.1, range: 8-21). Two-thirds of youth identified on the trans masculine spectrum ( n =90), 28.8% identified on the trans feminine spectrum ( n =40), and 6.5% identified as nonbinary/gender nonconforming ( n =9). Nearly, all youth had socially transitioned ( n =121, 87.7%) and were medically transitioning ( n =123, 89.1%). Conclusion: As one of the first rural-based registries, the GWC Registry has helped to delineate health outcomes attributable to gender-affirming care in a unique patient population of TG/GE youth. Our results will be used to describe treatment outcomes that will contribute to evidence-based guidelines., Competing Interests: No competing financial interests exist.

We have investigated current-current correlations in a cross-shaped conductor made of graphene. The mean free path of charge carriers is on the order of the ribbon width which leads to a hybrid conductor where there is diffusive transport in the device arms while the central connection region displays near ballistic transport. Our data on auto and cross correlations deviate from the predictions of Landauer-Büttiker theory, and agreement can be obtained only by taking into account contributions from non-thermal electron distributions at the inlets to the semiballistic center, in which the partition noise becomes strongly modified. The experimental results display distinct Hanbury - Brown and Twiss (HBT) exchange correlations, the strength of which is boosted by the non-equilibrium occupation-number fluctuations internal to this hybrid conductor. Our work demonstrates that variation in electron coherence along atomically-thin, two-dimensional conductors has significant implications on their noise and cross correlation properties.

MicroRNA (miRNA)s are dysregulated in Diffuse large B-cell lymphoma (DLBCL), where they reflect the malignant B-cells and the immune infiltrate within the tumor microenvironment. There remains a paucity of data in DLBCL regarding cell-free (c-f) miRNA as disease response biomarkers. Immunosuppressive monocyte/macrophages, which are enriched in DLBCL, are disease response markers in DLBCL, with miRNA key regulators of their immunosuppressive function. Our aim was to determine whether plasma miRNA that reflect the activity of the malignant B-cell and/or immunosuppressive monocytes/macrophages, have value as minimally-invasive disease response biomarkers in DLBCL. Quantification of 99 DLBCL tissues, to select miRNA implicated in immunosuppressive monocytes/macrophage biology, found miR-494 differentially elevated. In a discovery cohort (22 patients), pre-therapy c-f miR-494 and miR-21 but not miR-155 were raised relative to healthy plasma. Both miR-494 and miR-21 levels 3-6 months reduced post immuno-chemotherapy. The validation cohort (56 patients) was from a prospective clinical trial. Interestingly, in sequential samples both miRNAs decreased in patients becoming Positron Emission Tomography/Computerized Tomography (PET/CT)-ve, but not in those remaining interim-PET/CT+. Patient monocytes were phenotypically and functionally immunosuppressive with ex-vivo monocyte depletion enhancing T-cell proliferation in patient but not healthy samples. Pre-therapy monocytes showed an immunosuppressive transcriptome and raised levels of miR-494. MiR-494 was present in all c-f nanoparticle fractions but was most readily detectable in unfractionated plasma. Circulating c-f miR-494 and miR-21 are disease response biomarkers with differential response stratified by interim-PET/CT in patients with DLBCL. Further studies are required to explore their manipulation as potential therapeutic targets., Competing Interests: CONFLICTS OF INTEREST The authors declare that no competing financial interests exists.

Self-inflicted deaths in prisons in England and Wales, recently reported as the highest in over a decade, are a significant cause of mortality. A lack of guidelines surrounding the screening and identification of suicide risk of new prisoners along with a dearth of effective screening tools indicate the need for review. Our aims are to examine findings on the effectiveness of prison specific suicide screening tools used with adult prisoners. Papers were identified via systematic searches of databases, scanning grey literature, and reference checking. Included studies were published over the period between 2000-2016. PRISMA guidelines were followed. Studies were selected based on population - adult imprisoned offenders; intervention - suicide screening tool; comparators - participants screened vs. not screened outcome - suicide or attempted suicide. Data was extracted manually. A narrative synthesis presented the findings between different screening tools. Eight screening tools were critically appraised. Evidence suggested that the VISCI and Dutch screening tools are most effective in identifying those at risk and reducing suicide and/or self-harm behavior. Variance in methodological quality and associated factors indicate the need for further development of prospective studies to develop robust screening tools. This study is registered with PROSPERO (CRD42016035471).

Burning solid fuels to fulfill daily household energy needs results in chronic exposure to household air pollution (HAP), which is among the world's greatest health risks. This paper presents the results of a cross-sectional study of cookstove usage, fuel consumption, and indoor PM 2.5 concentrations in rural and urban Honduran homes cooking with the Envirofit HM-5000 metal plancha stove (n = 32) as compared to control households using baseline cooking technologies (n = 33). Temperature-based stove usage measurements showed high HM-5000 acceptance, with significant displacement of the traditional cookstoves at both the urban (99%, P < .05) and rural study sites (75%, P < .05). However, longer-term usage data collected in peri-urban households showed that participants cooked on the HM-5000 more frequently during the 3-day monitoring period than during the following 3 weeks. Average indoor PM 2.5 was 66% lower in HM-5000 households as compared to control households (P < .05). Lower indoor PM 2.5 concentrations observed in participant homes as compared to control households, supported by high usage and traditional stove displacement, suggest the potential for the HM-5000 to yield health improvements in adopting Honduran households., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Outbreaks of health care-associated infections (HAIs) caused by Burkholderia cepacia complex (Bcc) have been associated with medical devices and water-based products. Water is the most common raw ingredient in nonsterile liquid drugs, and the significance of organisms recovered from microbiologic testing during manufacturing is assessed using a risk-based approach. This incident demonstrates that lapses in manufacturing practices and quality control of nonsterile liquid drugs can have serious unintended consequences., Methods: An epidemiologic and laboratory investigation of clusters of Bcc HAIs that occurred among critically ill, hospitalized, adult and pediatric patients was performed between January 1, 2016, and October 31, 2016., Results: One hundred and eight case patients with Bcc infections at a variety of body sites were identified in 12 states. Two distinct strains of Bcc were obtained from patient clinical cultures. These strains were found to be indistinguishable or closely related to 2 strains of Bcc obtained from cultures of water used in the production of liquid docusate, and product that had been released to the market by manufacturer X., Conclusions: This investigation highlights the ability of bacteria present in nonsterile, liquid drugs to cause infections or colonization among susceptible patients. Prompt reporting and thorough investigation of potentially related infections may assist public health officials in identifying and removing contaminated products from the market when lapses in manufacturing occur., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.)

Much focus has been on the interaction of programmed cell death ligand 1 (PD-L1) on malignant B cells with programmed cell death 1 (PD-1) on effector T cells in inhibiting antilymphoma immunity. We sought to establish the contribution of natural killer (NK) cells and inhibitory CD163 + monocytes/macrophages in Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). Levels of PD-1 on NK cells were elevated in cHL relative to DLBCL. Notably, CD3 - CD56 hi CD16 -ve NK cells had substantially higher PD-1 expression relative to CD3 - CD56 dim CD16 + cells and were expanded in blood and tissue, more marked in patients with cHL than patients with DLBCL. There was also a raised population of PD-L1-expressing CD163 + monocytes that was more marked in patients with cHL compared with patients with DLBCL. The phenotype of NK cells and monocytes reverted back to normal once therapy (ABVD [doxorubicin 25 mg/m 2 , bleomycin 10 000 IU/m 2 , vinblastine 6 mg/m 2 , dacarbazine 375 mg/m 2 , all given days 1 and 15, repeated every 28 days] or R-CHOP [rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m 2 IV, doxorubicin 50 mg/m 2 IV, vincristine 1.4 mg/m 2 (2 mg maximum) IV, prednisone 100 mg/day by mouth days 1-5, pegfilgrastim 6 mg subcutaneously day 4, on a 14-day cycle]) had commenced. Tumor-associated macrophages (TAMs) expressed high levels of PD-L1/PD-L2 within diseased lymph nodes. Consistent with this, CD163/PD-L1/PD-L2 gene expression was also elevated in cHL relative to DLBCL tissues. An in vitro functional model of TAM-like monocytes suppressed activation of PD-1 hi NK cells, which was reversed by PD-1 blockade. In line with these findings, depletion of circulating monocytes from the blood of pretherapy patients with cHL and patients with DLBCL enhanced CD3 - CD56 hi CD16 -ve NK-cell activation. We describe a hitherto unrecognized immune evasion strategy mediated via skewing toward an exhausted PD-1-enriched CD3 - CD56 hi CD16 -ve NK-cell phenotype. In addition to direct inhibition of NK cells by the malignant B cell, suppression of NK cells can occur indirectly by PD-L1/PD-L2-expressing TAMs. The mechanism is more prominent in cHL than DLBCL, which may contribute to the clinical sensitivity of cHL to PD-1 blockade., (© 2018 by The American Society of Hematology.)

Purpose: Defining the risk of neoplasia associated with gender-affirming hormone therapy (GAHT) is a priority for transgender medical research. The purposes of this article are to present a unique case of breast neoplasia in a transgender individual and to review the existing evidence base on GAHT as a potential risk for breast pathology. Methods: We present the case of a 76-year-old transgender patient who developed an estrogen receptor-positive mammary myofibroblastoma (MFB) after 13 months of treatment on feminizing hormones. To our knowledge, this is the first reported case of MFB occurring in a transgender individual. A literature review was conducted to identify all reported cases of breast neoplasia among transgender individuals receiving feminizing GAHT. Information was abstracted from each of the included cases to describe the existing body of literature and to compare published cases to the case reported in this study. Results: We identified a total of 19 malignant and 3 benign cases of breast neoplasia among transgender women. Ours is the first reported case of MFB in a transgender individual receiving feminizing hormones and the first reported case of breast neoplasia associated with GAHT administered via the estradiol patch. Conclusion: This case reinforces the need for additional reporting of breast neoplasia presenting in transgender individuals treated with feminizing hormones. The relationship between estrogen exposure and breast neoplasia in the transgender population remains poorly defined, and additional research is needed to define risks and inform clinical practice., Competing Interests: No competing financial interests exist.

Introduction: The 2015-2017 Zika virus (ZIKV) epidemic in the Americas has driven efforts to strengthen surveillance systems and to develop interventions, testing, and travel recommendations. In the continental U.S. and Hawaii, where limited transmission has been observed, detecting local transmission is a key public health objective. We assessed the effectiveness of three general surveillance strategies for this situation: testing all pregnant women twice during pregnancy, testing blood donations, and testing symptomatic people who seek medical care in an emergency department (ED)., Methods: We developed a simulation model for each surveillance strategy and simulated different transmission scenarios with varying population sizes and infection rates. We then calculated the probability of detecting transmission, the number of tests needed, and the number of false positive test results., Results: The probability of detecting ZIKV transmission was highest for testing ED patients with Zika symptoms, followed by pregnant women and blood donors, in that order. The magnitude of the difference in probability of detection between strategies depended on the incidence of infection. Testing ED patients required fewer tests and resulted in fewer false positives than surveillance among pregnant women. The optimal strategy identified was to test ED patients with at least two Zika virus disease symptoms. This case definition resulted in a high probability of detection with relatively few tests and false positives., Discussion: In the continental U.S. and Hawaii, where local ZIKV transmission is rare, optimizing the probability of detecting infections while minimizing resource usage is particularly important. Local surveillance strategies will be influenced by existing public health system infrastructure, but should also consider the effectiveness of different approaches. This analysis demonstrated differences across strategies and indicated that testing symptomatic ED patients is generally a more efficient strategy for detecting transmission than routine testing of pregnant women or blood donors.

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.