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Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome that complicates hematopoietic stem cell transplant (HSCT). Morbidity and mortality from TA-TMA remain high, making prevention critical. We describe our retrospective single-center experience of TA-TMA after pediatric allogeneic HSCT and present a novel pre-HSCT risk-stratification system and prophylaxis regimen. From January 2012 through October 2019, 257 patients underwent 292 allogeneic HSCTs. Prospective risk stratification was introduced in December 2016. High-risk (HR) patients were treated with combination prophylaxis with eicosapentaenoic acid and N-acetylcysteine. The 1-year cumulative incidence of TA-TMA was 6.3% (95% confidence interval [CI], 3.2-9.4). Age ≥10 years, myeloablative conditioning with total body irradiation, HLA mismatch, diagnosis of severe aplastic anemia or malignancy, prior calcineurin inhibitor exposure, and recipient cytomegalovirus seropositivity were found to be pre-HSCT risk factors for development of TA-TMA. Before routine prophylaxis, TA-TMA rates were significantly different between the HR and standard-risk groups, at 28.2% (95% CI, 0-12.7) vs 3.2% (0.1-6.3), respectively (P < .001). After introduction of prophylaxis, the 1-year cumulative incidence of TA-TMA in the HR group decreased to 4.5% (95% CI, 0-13.1; P = .062, compared with the incidence before prophylaxis). Multicenter pediatric studies are needed to validate these risk criteria and to confirm the efficacy of the prophylactic regimen.

Research conducted across phylogeny on cardiac regenerative responses following heart injury implicates endocrine signaling as a pivotal regulator of both cardiomyocyte proliferation and heart regeneration. Three prominently studied endocrine factors are thyroid hormone, vitamin D, and glucocorticoids, which canonically regulate gene expression through their respective nuclear receptors thyroid hormone receptor, vitamin D receptor, and glucocorticoid receptor. The main animal model systems of interest include humans, mice, and zebrafish, which vary in cardiac regenerative responses possibly due to the differential onsets and intensities of endocrine signaling levels throughout their embryonic to postnatal organismal development. Zebrafish and lower vertebrates tend to retain robust cardiac regenerative capacity into adulthood while mice and other higher vertebrates experience greatly diminished cardiac regenerative potential in their initial postnatal period that is sustained throughout adulthood. Here, we review recent progress in understanding how these three endocrine signaling pathways regulate cardiomyocyte proliferation and heart regeneration with a particular focus on the controversial findings that may arise from different assays, cellular-context, age, and species. Further investigating the role of each endocrine nuclear receptor in cardiac regeneration from an evolutionary perspective enables comparative studies between species in hopes of extrapolating the findings to novel therapies for human cardiovascular disease.

AlN devices have the potential to outperform current GaN devices, especially in the high-voltage region, thanks to AlN’s larger critical electric field and thermal conductivity. In order for the AlN-based power diodes to be realized and performance to be demonstrated, high-quality AlN crystals would be the prerequisite. In this article, significantly improved AlN quality has been demonstrated through high-temperature treatment of AlN thin layers at high temperatures in the range of 1670–1730 °C, followed by regrowth of AlN layers on top. The produced AlN layer shows much improved crystalline quality when compared to AlN layer without thermal treatment. The thermal treatment of AlN nucleation layers recrystallizes the AlN materials and results in a significant reduction of the full-width at half-maximum (FWHM) values of X-ray rocking curves of AlN (002) and (102) planes. The annealing of AlN nucleation also produced much pronounced atomic step features and improves the transmittance for the nucleation layers. Regrowth of AlN templates on such annealed nucleation improves AlN crystalline quality further, producing high-quality templates for power diode applications.

Allogeneic hematopoietic cell transplantation (HCT) for children with nonmalignant disorders is challenged by potential drug-related toxicities and poor engraftment. This retrospective analysis expands on our single pediatric medical center experience with targeted busulfan, fludarabine, and intravenous (IV) alemtuzumab as a low-toxicity regimen to achieve sustained donor engraftment. Sixty-two patients received this regimen for their first HCT for a nonmalignant disorder between 2004 and 2018. Donors were matched sibling in 27%, 8/8 HLA allele-matched unrelated in 50%, and 7/8 HLA allele-mismatched in 23% (some of whom received additional immunoablation with thiotepa or clofarabine). Five patients experienced graft failure for a cumulative incidence of 8.4% (95% CI, 1 to 16%). In engrafted patients, the median donor chimerism in whole blood and CD3, CD14/15, and CD19 subsets at 1-year were 96%, 90%, 99%, and 99%, respectively. Only one patient received donor lymphocyte infusions (DLIs) for poor chimerism. Two patients died following disease progression despite 100% donor chimerism. The 3-year cumulative incidence of treatment-related mortality was 10% (95% CI, 2 to 17%). Overall survival and event-free-survival at 3-years were 87% (95% CI, 78 to 95%) and 80% (95% CI, 70 to 90%), respectively. The 6-month cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 7% (95% CI, 3 to 13%), while the 3-year cumulative incidence of chronic GVHD was 5% (95% CI, 0 to 11%). These results suggest that use of targeted busulfan, fludarabine and IV alemtuzumab offers a well-tolerated option for children with nonmalignant disorders to achieve sustained engraftment with a low incidence of GVHD.

Background Exposure to fine particulate matter (with an aerodynamic diameter ≤ 2·5 μm, PM2·5 ) air pollution has been associated with skin-related diseases or disorders. Objectives To evaluate the potential skin-protective effects of fish-oil supplementation against PM2·5 exposure. Materials and methods This is an exploratory analysis based on a pilot randomized, double-blind, placebo-controlled trial among 65 healthy young adults between September 2017 and January 2018 in Shanghai, China. We randomly assigned participants to take either fish oil or placebo 2·5 g daily for four consecutive months. Four rounds of skin D-Squame® tape samples were collected in the last 2 months, and five secondary biomarkers of skin inflammation and oxidative stress were measured. Fixed-site PM2·5 concentrations on campus were measured in real time. We used linear mixed-effect models to analyse the associations between short-term PM2·5 exposure and biomarkers in each group. Results The 24-h average PM2·5 concentration was 34·68 ± 15·83 μg m-3 . There were generally weaker associations between PM2·5 and biomarkers in the fish-oil group than in the placebo group, but the associations and the between-group differences varied by biomarkers and lag periods. Compared with the placebo group, for a 10-μg m-3 increase in PM2·5 concentration, the increments of interleukin-1α and carbonyl protein in the fish-oil group were 41·55% smaller [95% confidence interval (CI) 4·61-78·48%] at lag 0-48 h and 22·01% smaller (95% CI 11·25-32·77%) at lag 0-24 h, respectively. No significant between-group differences were observed for other biomarkers. Conclusions This study suggested that dietary fish-oil supplementation may improve biomarkers of skin inflammation and oxidative-stress response to short-term PM2·5 exposure.

Frequency-domain multiplexing (fMux) is an established technique for the readout of large arrays of transition edge sensor (TES) bolometers. Each TES in a multiplexing module has a unique AC voltage bias that is selected by a resonant filter. This scheme enables the operation and readout of multiple bolometers on a single pair of wires, reducing thermal loading onto sub-Kelvin stages. The current receiver on the South Pole Telescope, SPT-3G, uses a 68x fMux system to operate its large-format camera of $\sim$16,000 TES bolometers. We present here the successful implementation and performance of the SPT-3G readout as measured on-sky. Characterization of the noise reveals a median pair-differenced 1/f knee frequency of 33 mHz, indicating that low-frequency noise in the readout will not limit SPT-3G's measurements of sky power on large angular scales. Measurements also show that the median readout white noise level in each of the SPT-3G observing bands is below the expectation for photon noise, demonstrating that SPT-3G is operating in the photon-noise-dominated regime., Comment: 9 pages, 5 figures submitted to the Journal of Low Temperature Physics: LTD18 Special Edition

To determine the genetic correlates of physical frailty and sarcopenia, focusing on single nucleotide polymorphisms (SNPs) in genome-wide association studies (GWAS), and to explore the genetic overlap of frailty with cardiovascular disease (CVD) and its risk factors. PubMed was systematically searched for GWAS studies investigating the association between SNPs and objective measures of physical frailty or sarcopenia. SNPs were retained if they were associated with one of the phenotypes of interest by a p-value of 5.0×10−8 or less. Ten studies were included, with a total of 237 SNPs in 181 genes being associated with physical frailty or sarcopenia; as measured by handgrip strength or lean (muscle) mass. These genes were cross-referenced in the GWAS Catalog, and many of them were found to be associated with CVD or metabolic syndrome. Evidence from GWAS has shown that frailty is associated with common genetic polymorphisms. Many of these polymorphisms have been implicated in CVD, supporting the hypothesis of a shared pathophysiology between these entities. Future studies are eagerly anticipated to map out the mechanistic links and discover therapeutic targets and novel biomarkers for frailty.

The North American Pediatric Aplastic Anemia Consortium (NAPAAC) is a group of pediatric hematologist-oncologists, hematopathologists, and bone marrow transplant physicians from 46 institutions in North America with interest and expertise in aplastic anemia, inherited bone marrow failure syndromes, and myelodysplastic syndromes. The NAPAAC Bone Marrow Failure Diagnosis and Care Guidelines Working Group was established with the charge of harmonizing the approach to the diagnostic workup of aplastic anemia in an effort to standardize best practices in the field. This document outlines the rationale for initial evaluations in pediatric patients presenting with signs and symptoms concerning for severe aplastic anemia.

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein is a cAMP-activated anion channel that is critical for regulating fluid and ion transport across the epithelium. This process is disrupted in CF epithelia, and patients harbouring CF-causing mutations experience reduced lung function as a result, associated with the increased rate of mortality. Much progress has been made in CF research leading to treatments that improve CFTR function, including small molecule modulators. However, clinical outcomes are not necessarily mutation-specific as individuals harboring the same genetic mutation may present with varying disease manifestations and responses to therapy. This suggests that the CFTR protein may have alternative functions that remain under-appreciated and yet can impact disease. In this mini review, we highlight some notable research implicating an important role of CFTR protein during early lung development and how mutant CFTR proteins may impact CF airway disease pathogenesis. We also discuss recent novel cell and animal models that can now be used to identify a developmental cause of CF lung disease.

This chapter discusses social media use and community resilience development during the Coronavirus disease (COVID-19) pandemic in Singapore. It investigates how social media affects citizens' self-resilience capacities during various stages of the COVID-19 pandemic evolution, in particular, in terms of information gathering, information dissemination, information exchange, collaborative problem-solving, coping and promotion of connectedness in order to derive opportunities and challenges for community resilience building. The COVID-19 pandemic has unleashed unprecedented disruption to economy and society. Social media has become an integral part of many people's everyday lives. Social networking can influence citizens' self-reliance in the event of a crisis by providing avenues for getting quick and reliable information that reduces uncertainty. Singapore won praise from the World Health Organisation for its early response to dealing with COVID-19 pandemic without the need for enforced lockdowns.

SPT-3G is a polarization-sensitive receiver, installed on the South Pole Telescope, that measures the anisotropy of the cosmic microwave background (CMB) from degree to arcminute scales. The receiver consists of ten 150~mm-diameter detector wafers, containing a total of 16,000 transition-edge sensor (TES) bolometers observing at 95, 150, and 220 GHz. During the 2018-2019 austral summer, one of these detector wafers was replaced by a new wafer fabricated with Al-Mn TESs instead of the Ti/Au design originally deployed for SPT-3G. We present the results of in-lab characterization and on-sky performance of this Al-Mn wafer, including electrical and thermal properties, optical efficiency measurements, and noise-equivalent temperature. In addition, we discuss and account for several calibration-related systematic errors that affect measurements made using frequency-domain multiplexing readout electronics., Comment: 9 pages, 5 figures, submitted to the Journal of Low Temperature Physics: LTD18 Special Edition

Objective To report on the prevalence and etiology of pediatric anemia in the Commonwealth of the Northern Mariana Islands (CNMI). Method A retrospective chart review was conducted that included patients up to 19 years of age who presented for well child care and whose hemoglobin or hematocrit was checked in the CNMI from 2014 to 2015. Lab values, diagnoses and treatment plans, patient reported ethnicity, and follow-up results were collected from eligible patients. Results The records for 1483 pediatric patients who had 1584 well child visits were reviewed. The prevalence of anemia amongst all eligible patients was 8.0% (5.4-10.7). This included 292 9 to 18 months old patients, which is estimated to be 40% of the total pediatric population of CNMI in that age group. Among the 9 to 18 months old patients, the prevalence of anemia is 5.5% (2.6-8.4). Etiology of anemia was investigated and of the patients treated with iron, 55.2% had a documented response. The majority of those without documentation of improvement with iron were patients who were lost to follow-up. In addition, a total of 10 patients were found to have an alpha or beta thalassemia variant discovered initially by anemia screening or sibling tracing. Discussion In this United States Commonwealth, prevalence of anemia appears lower than prevalence reported for other independent Pacific Island nations and closer to that of the US. Thalassemia is documented within this population. Limitations to this data were use of a convenient sample that may be hampered by lack of presentation to well-child care. This study will guide future public health studies on anemia prevalence and can guide public health intervention decisions to improve pediatric care in the CNMI.

Galaxy clusters identified from the Sunyaev Zel'dovich (SZ) effect are a key ingredient in multi-wavelength cluster-based cosmology. We present a comparison between two methods of cluster identification: the standard Matched Filter (MF) method in SZ cluster finding and a method using Convolutional Neural Networks (CNN). We further implement and show results for a `combined' identifier. We apply the methods to simulated millimeter maps for several observing frequencies for an SPT-3G-like survey. There are some key differences between the methods. The MF method requires image pre-processing to remove point sources and a model for the noise, while the CNN method requires very little pre-processing of images. Additionally, the CNN requires tuning of hyperparameters in the model and takes as input, cutout images of the sky. Specifically, we use the CNN to classify whether or not an 8 arcmin $\times$ 8 arcmin cutout of the sky contains a cluster. We compare differences in purity and completeness. The MF signal-to-noise ratio depends on both mass and redshift. Our CNN, trained for a given mass threshold, captures a different set of clusters than the MF, some of which have SNR below the MF detection threshold. However, the CNN tends to mis-classify cutouts whose clusters are located near the edge of the cutout, which can be mitigated with staggered cutouts. We leverage the complementarity of the two methods, combining the scores from each method for identification. The purity and completeness of the MF alone are both 0.61, assuming a standard detection threshold. The purity and completeness of the CNN alone are 0.59 and 0.61. The combined classification method yields 0.60 and 0.77, a significant increase for completeness with a modest decrease in purity. We advocate for combined methods that increase the confidence of many lower signal-to-noise clusters.

BACKGROUND To improve the quality of pre-analytical phase and provide targeted suggestions, this study analyzed factors causing unqualified clinical specimens in patients of the Department of Clinical Laboratory of Renmin Hospital of WuHan University from 2015 to 2019. METHODS Inpatient specimens from January 2015 to December 2019 were retrospectively analyzed. Unqualified specimens were identified by referring to the general principle of rejection. The analytical indicators included incidence rate of unqualified specimens and constituent ratio of reasons of unqualified specimens. These two indicators were analyzed according to the inpatient wards and types of specimens. RESULTS From 2015 to 2019, 21,674 inpatient unqualified specimens were collected, the incidence rate of unqualified specimens was 0.22% (21,674/9,700,869), the number and rate of unqualified specimens decreased year by year. The main reasons of unqualified specimens were insufficient volume (29.67%, 6,430/21,674) and clotting (26.31%, 5,703/21,674). The number of unqualified specimens in the departments of cardiovascular, pediatrics, neurology, oncology, urinary surgery, and intensive care unit ranked the top each year. Clotting (39.29%, 5,682/14,462) was the main reason of unqualified blood specimens while insufficient volume (71.18%, 3,365/4,727) was for urine specimens. Wrong identification caused unqualified feces (62.65%, 728/1,162) and body fluid (40.74%, 539/1,323) specimens. CONCLUSIONS Clinical laboratory could make effective measures to improve pre-analytical quality by retrospectively analyzing data of unqualified specimens.

Background Recent data show survival after matched unrelated donor (MUD) bone marrow transplantation (BMT) is similar to matched sibling procedures for young patients with severe aplastic anemia (SAA). Donor delays, risk of transplant-related mortality (TRM), and concern about chronic graft versus host disease raise questions about whether MUD BMT or immune suppression therapy (IST) should be preferred initial therapy for young patients lacking matched sibling donors. Procedure We performed a pilot trial to assess the feasibility of randomizing patients under age 26 with newly diagnosed SAA to receive IST versus MUD BMT. Primary aims assessed the acceptability of randomization and timing of BMT. Secondary aims measured toxicities, response, and survival. Results Sixty-seven patients with possible SAA were screened at nine centers. Of 57 with confirmed SAA, 23 underwent randomization and received therapy with a median follow-up of 18 months. Of 12 randomized to BMT, 10 started BMT as initial therapy at a median of 36 days after randomization. One BMT recipient experienced secondary graft failure, requiring a second procedure. Six of 11 randomized to IST responded, whereas five with refractory disease underwent successful salvage BMT. One patient achieving complete response relapsed after discontinuation of immune suppression and died of infection after salvage BMT. Conclusions This feasibility study showed that a high percentage of patients underwent randomization and received up-front MUD BMT. Our study lays the groundwork for a larger randomized trial that will define best initial therapy for young patients with SAA who have an available MUD.

Background This study aimed to evaluate delta check limits set by reference change value (RCV) and patient data. Methods Patient data of 11 clinical chemistry analytes from June 2018 to May 2019 were collected. RCV with 95% or 99% levels of probability were calculated based on biological variation. The corresponding delta check limits for outpatients and inpatients were calculated by 95% or 99% central range of delta% which was the difference of two consecutive results within thirty days of the same patient for each analyte. Patient data in June 2019 were used to analyze the utility of delta check limits. Results In total, 434,927 paired results for these 11 analytes were included. The delta check limits were different between outpatients and inpatients, but were wider than those established by RCV. The difference between Glu's outpatient and inpatient boundaries was the largest, 95% central range from the outpatient (inpatients) was from -32.29% (-56.97%) to 38.78% (106.00%) while 99% central range from the outpatient (inpatients) was from -56.86% (-90.56%) to 89.96% (262.54%). The RCV is mainly determined by within-individual biological variation so that the RCV of each analyte varied from each other. As for RCV, Na had the lowest value and BUN had the highest one. In addition, the main reason for delta% exceeding delta check limits was a clinically significant change. Conclusions Laboratories could use delta check procedure to find out errors in sample collection and monitor clinical significance. When delta% of patients exceed corresponding delta check limits in a short time, clinicians and personnel of clinical laboratory should pay more attention. Delta check limits should be reviewed regularly to check the utility of procedure.

Aim To evaluate Tmax, defined as the time of residual function R(t) reaching its maximum, as an indicator of myocardial ischaemia and compare its efficacy with other computed tomography perfusion (CTP) parameters. Materials and methods Eight Bama miniature pigs with 50–90% left anterior descending artery stenosis underwent adenosine stress myocardial CTP and 13N NH3 position-emission tomography (PET) perfusion imaging. Tmax, myocardial blood flow (MBF), myocardial blood volume (MBV), mean transit time (MTT), and time to peak (TTP) were calculated from CTP images. PET images were evaluated as ischaemia or non-ischaemia. Using PET as a reference standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Multiple comparisons of the receiver operating characteristic (ROC) curves between Tmax and other parameters were performed. The diagnostic performance of the combination of each two parameters was calculated and compared with Tmax. Results Tmax was significantly higher in ischaemic segments compared with non-ischaemic segments. Multiple comparisons of the ROCs indicated that Tmax was better than MBF or TTP but not statistically different from MBV. Tmax was superior to the combination of (MBF + MBV) but not to (MBF + TTP) or (MBV + TTP). Conclusion Tmax in dynamic stress CTP provides good diagnostic accuracy for detecting myocardial ischaemia, especially in sensitivity and NPV, compared with PET method. Tmax has better performance than MBF or TTP or combination of (MBF + MBV) in diagnosing myocardial ischaemia.

In this work, we have measured the properties of membrane-suspended bolometer thermal links and microstrip transmission lines in the transition-edge sensor arrays for the third-generation camera for South Pole Telescope (SPT-3G). A promising technique for controlling the end point of the release etch that defines the thermal link has been developed. We have also evaluated the microstrip loss in our detectors by measuring the optical efficiency of detectors with different lengths of microstrip line. The loss tangent is sufficiently low for the use in multi-chronic pixels for cosmic microwave background instruments like SPT-3G.

Objectives To examine the effects of early comprehensive interventions on home environment and child neurodevelopment among children younger than 3 years in poor rural areas of China, as well as the underlying mediating and moderating mechanisms. Study design Non-randomized intervention study was conducted among 216 children aged 0–3 years in Shanxi province of China. Based on a 2 × 2 factor design, children in Lin and Fenxi County were assigned to an intervention group with duration less than 1 year (n = 26) or an intervention group with duration longer than 1 year (n = 82), while children in Fangshan County served as a control group with duration less than 1 year (n = 30) or a control group with duration longer than 1 year (n = 78). Methods The control group received national public health services (NPHS), while the intervention group received NPHS plus comprehensive interventions covering health, nutrition, early psychosocial stimulation, and child protection. Home environment (Infant-Toddler Home Observation for Measurement of the Environment [HOME]) and child neurodevelopment (Ages and Stages Questionnaire [ASQ]) were measured by observation and interview with mothers after the intervention program. Results The intervention group showed significantly higher overall HOME, organization, learning materials, and involvement than the control group, only for a duration longer than 1 year. Children in the intervention group performed better in overall ASQ, fine motor, problem-solving, and personal-social than children in the control group. Moderated mediation analyses indicated that there were significantly indirect effects of treatment on overall ASQ through overall HOME, organization, and involvement only when the duration was longer than 1 year. Conclusions Early comprehensive interventions longer than 1 year improve home environment and promote child neurodevelopment among children younger than 3 years in poor rural areas. What is more, effects of early comprehensive interventions longer than 1 year on child neurodevelopment were mediated by home environment.

The third-generation upgrade to the receiver on the South Pole Telescope, SPT-3G, was installed at the South Pole during the 2016–2017 austral summer to measure the polarization of the cosmic microwave background. Increasing the number of detectors by a factor of 10 to ∼16,000 \ud ∼16,000\ud required the multiplexing factor to increase to 68 and the bandwidth of the frequency-division readout electronics to span 1.6–5.2 MHz. This increase necessitates low-thermal conductance, low-inductance cryogenic wiring. Our cold readout system consists of planar thin-film aluminum inductive–capacitive resonators, wired in series with the detectors, summed together, and connected to 4K SQUIDs by 10−μm \ud 10−μm\ud -thick niobium–titanium (NbTi) broadside-coupled striplines. Here, we present an overview of the cold readout electronics for SPT-3G, including assembly details and characterization of electrical and thermal properties of the system. We report, for the NbTi striplines, values of R≤10 −4 Ω \ud R≤10−4Ω\ud , L=21±1 nH \ud L=21±1 nH\ud , and C=1.47±.02 nF \ud C=1.47±.02 nF\ud . Additionally, the striplines’ thermal conductivity is described by kA=6.0±0.3 T 0.92±0.04 μW mm K −1 \ud kA=6.0±0.3 T0.92±0.04 μW mm K−1\ud . Finally, we provide projections for cross talk induced by parasitic impedances from the stripline and find that the median value of percentage cross talk from leakage current is 0.22 and 0.09% \ud 0.09%\ud from wiring impedance.

The South Pole Telescope third-generation (SPT-3G) receiver was installed during the austral summer of 2016–2017. It is designed to measure the cosmic microwave background across three frequency bands centered at 95, 150, and 220 GHz. The SPT-3G receiver has ten focal plane modules, each with 269 pixels. Each pixel features a broadband sinuous antenna coupled to a niobium microstrip transmission line. In-line filters define the desired band-passes before the signal is coupled to six bolometers with Ti/Au/Ti/Au transition edge sensors (three bands × \ud ×\ud two polarizations). In total, the SPT-3G receiver is composed of 16,000 detectors, which are read out using a 68× \ud ×\ud frequency-domain multiplexing scheme. In this paper, we present the process employed in fabricating the detector arrays.

We examined national trends in the receipt of specialty outpatient mental health care, using data for 2008-15 from the National Survey on Drug Use and Health. Between 2008-09 and 2014-15 the number of US adults who received outpatient mental health care in the specialty sector rose from 11.3 million to 13.7 million per year, representing an increase from 5.0 percent to 5.7 percent of the adult population. Among those recipients, however, the annual weighted mean number of visits to the specialty sector remained unchanged. We found increases in both numbers and percentages of adults who received care within the specialty sector across age and sex groups and among non-Hispanic whites, people with Medicare, people with private health insurance, and people with family incomes of $20,000-$49,999. Increases in receipt of specialty mental health care during 2012-15 may be related to recent policy initiatives aimed at reducing financial barriers to care.

Background: Coagadex is a high-purity plasma-derived factor X concentrate (pdFX) developed to treat hereditary factor X deficiency (FXD). Objective: Evaluate the efficacy and safety of pdFX administered to patients with hereditary FXD. Methods: This was an open-label, multicenter, retrospective analysis of patients receiving pdFX for compassionate use. Efficacy end points included treatments administered, the number and treatment of bleeds, and investigator assessments. Adverse drug reactions (ADRs) were monitored. Results: Fifteen patients were included: seven received routine prophylaxis, seven received on-demand treatment, and one alternated. Most were aged ?12 years (n = 13) and had severe hereditary FXD (n = 12). The median follow-up time was 19.2 months (range, 3.5-48.8). The number of infusions per patient per month was higher for the routine prophylaxis group (median [range], 5.4 [1.4-10.1]) than for the on-demand group (0.8 [0.1-2.3]), as was the dose per infusion (27.9 [21.9-53.6] IU/kg vs 20.0 [13.6-27.7] IU/kg). Patients experienced 88 bleeds (34 minor, 7 major, 47 unclassified). The monthly bleed rate per patient was 0.04 in the routine prophylaxis group (based on 17 bleeds in four patients) and 0.8 in the on-demand group (based on 71 bleeds in eight patients). pdFX was used to treat 79 bleeds and was rated effective in all instances. In an overall assessment, investigators rated pdFX as excellent for 14 patients (93.3%) and good for 1 patient (6.3%). No ADRs or safety concerns were reported. Conclusions: This analysis supports the use of pdFX as a safe, effective treatment for hereditary FXD. Routine prophylaxis with pdFX may reduce bleed frequency. © 2021 Bio Products Laboratory. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH)., This study was funded by Bio Products Laboratory Ltd. Bio Products Laboratory (Elstree, UK) provided funding for medical writing and editorial assistance in the development of this manuscript. Mollie Marko, PhD (Ashfield MedComms, an Ashfield Health company, Middletown, CT, USA), drafted and revised the manuscript based on input from authors, and Joshua Safran (Ashfield MedComms) copyedited and styled the manuscript per journal requirements., This study was funded by Bio Products Laboratory Ltd.

Background: Transplant associated thrombotic microangiopathy (TA-TMA) is a known complication of hematopoietic stem cell transplant (HSCT) associated with endothelial injury that leads to end organ damage and high morbidity and mortality. No proven method for prevention of TA-TMA exists. One strategy is to decrease or even prevent the initial endothelial injury during conditioning. Defibrotide is an anti-inflammatory and anti-thrombotic agent that has been shown to protect the endothelium from damage and treat TA-TMA. We hypothesize that prophylactic use of defibrotide during HSCT conditioning and acute recovery may potentially prevent TA-TMA. Methods: We initiated a pilot single-arm phase II trial (NCT#03384693) to evaluate the safety and feasibility of administering prophylactic defibrotide to pediatric patients at high risk for the development of TA-TMA following HSCT. Additionally, we sought to determine if administration of prophylactic defibrotide would prevent the development of TA-TMA in clinically high-risk patients compared to historic controls. High-risk patients were defined as either patients with high-risk neuroblastoma whose treatment plan included autologous tandem transplants conditioned with cyclophosphamide/thiotepa (Cy/TT) and carboplatin/etoposide/melphalan (CEM), or allogeneic transplant patients undergoing myeloablative conditioning, with at least three of the following: age ≥10 years old, race/ethnicity other than Caucasian, ABO minor incompatibility, or haploidentical donor. Based on prior analysis at our center, we anticipated an incidence of TA-TMA of 28% in the high-risk patients undergoing allogeneic transplants and 40% in the neuroblastoma patients. Patients received defibrotide 6.25mg/kg IV q6h the day prior to the start of conditioning through day +21 and received supportive care per institution guidelines, including maintaining platelets above 30 x10^9/L. Patients were prospectively monitored for TA-TMA from admission through week 24. Results: Twenty-five patients were enrolled, 14 with neuroblastoma and 11 undergoing allogeneic HSCT. The median age was 3.45 (2.1-10.1) and 15.7 (0.8-27.4) years for autologous and allogeneic patients, respectively. Ten of the allogenic transplants were with an alpha-beta T-cell depleted haploidentical HSCT, while one was with a matched unrelated HSCT. Follow-up is complete on all patients. Defibrotide was stopped early due to clinically significant bleeding in 3 patients (day +3, +6 and +10, respectively). Bleeding episodes were excessive bleeding from oral hematoma, diffuse alveolar hemorrhage, and melanic stools and epistaxis and were classified as "possibly related" to the study drug. The other 22 patients missed a median of 0.7% of doses (0-5.2%), most often due to concomitant medication infusions. There were no allergic or hypersensitivity reactions. One patient with acute lymphoblastic leukemia (ALL) in CR4 died during the study period from respiratory failure in the setting of disseminated aspergillus and veno-occlusive disease (VOD), leading to a TRM of 0% and 9.1% in the autologous and allogeneic patients, respectively. Of the neuroblastoma patients, 4 did not go on to receive a second transplant; three due to development of moderate to severe VOD and one per parental preference. Five of the 14 neuroblastoma patients developed VOD, 4 after Cy/TT (1 mild, 2 moderate, 1 severe) and 1 after CEM (mild); all of which resolved. One patient developed non-severe TA-TMA, diagnosed 12 days post-HSCT (4% incidence). She received an alpha-beta T-cell depleted peripheral blood HSCT from her mother for ALL after conditioning with total body irradiation, cyclophosphamide, thiotepa, and ATG. Her course was complicated by diffuse alveolar hemorrhage on day +6 for which defibrotide was stopped. Her TA-TMA was treated with eculizumab and resolved without sequelae. Conclusions: 12% (3/25) patients required early discontinuation of defibrotide due to clinically significant bleeding; no other severe adverse events occurred due to the study intervention. The observed TA-TMA incidence of 4% was far below the anticipated rate of 28-40%. Our study provides preliminary evidence that defibrotide prophylaxis is safe and feasible in children and adolescents undergoing HSCT at high risk for TA-TMA and may reduce the risk of TA-TMA. Future larger randomized studies are needed to verify these findings. Disclosures Higham: Jazz Pharmaceuticals: Research Funding. Shimano:Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Daiichi Sankyo: Research Funding; Pfizer: Research Funding. OffLabel Disclosure: Defibrotide- off label use as prophylaxis for transplant associated thrombotic microangiopathy (TA-TMA)

Purpose Mouse orthotopic single lung transplantation (LTx) is a vital scientific model to explore lung transplantation (LTx) immunology. Minor alloantigen-mismatched LTx using C57BL/10 (B10, H-2b) to C57BL/6 (B6, H-2b) has mild acute rejection and sometimes chronic fibrosis, mimicking human LTx where alloimmunity is dampened by immunosuppressants. We have observed variations in allograft histology depending on individual microsurgeons’ experience. The purpose of this study was to compare pathological variations between individual surgeons and over time. Methods We performed a retrospective review of B10 to B6 LTx performed in our lab and sacrificed 28 days after LTx. LTx with an experimental intervention (e.g., usage of immunomodulatory agents or knock-out mice) were excluded. All pathological grading was performed in a blinded manner using HE B grade, Pl0.0001; % parenchymal fibrosis, P=0.1164; peri-airway fibrosis, Pl0.0001; obliterative airway fibrosis, Pl0.0001). Intra-surgeon chronological changes in pathological scores were statistically significant for A grade, B grade, and % parenchymal fibrosis (P=0.0024, P=0.0416, P=0.0097, respectively). Conclusion Mouse single lung transplantation is one of the most technically challenging animal models. It remains a powerful model to study underlying mechanisms of LTx biology. However, the significant learning curve and surgeon-dependent variability in histopathological findings need to be taken into account when designing experimental protocols.

BACKGROUND The incidence of endometrial cancer among young women is increasing. Some patients with low-grade endometrial cancer receive hormone therapy (HT) before surgery to preserve fertility. It is unclear whether this adversely affects survival. METHODS Patients with localized, low-grade endometrial cancer who were aged

Introduction Total body irradiation (TBI)-based conditioning is the standard of care in the treatment of acute lymphoblastic leukemia (ALL) that requires allogeneic hematopoietic stem cell transplantation (HSCT). However, TBI is known to be associated with an increased risk of late effects, and therefore, non-TBI regimens have also been utilized successfully. A recent study showed that patients that were next-generation sequencing-minimal residual disease (NGS-MRD) negative prior to allogeneic HSCT had a very low risk of relapse, and perhaps could avoid exposure to TBI without compromising disease control. We examined outcomes at our institution in patients that received a TBI or non-TBI regimen, as well as explored the impact of NGS-MRD status in predicting risk of relapse post transplant. Procedures This retrospective analysis included 57 children and young adults with ALL that received their first myeloablative allogeneic HSCT from 2012 to 2017 at the University of California San Francisco. Our primary endpoint was the cumulative incidence of relapse at 3 years post transplant. Results We demonstrated similar cumulative incidence of relapse for patients treated with either a TBI or non-TBI conditioning regimen, while NGS-MRD positivity prior to transplant was highly predictive of relapse. The presence of acute graft-versus-host disease was associated with decreased relapse rates, particularly among patients that received a TBI conditioning regimen and patients that were NGS-MRD positive prior to HSCT. Conclusions Our data suggest that the decision to use either a TBI or non-TBI regimens in ALL should depend on NGS-MRD status, with conditioning regimens based on TBI reserved for patients that cannot achieve NGS-MRD negativity prior to allogeneic HSCT.

Background: Autoimmune cytopenias (AICs) are potentially life-threatening complications following hematopoietic cell transplantation (HCT), yet little is understood about the mechanism by which they develop. We hypothesized that discordant B cell and T cell recovery is associated with AICs in transplant patients, and that this might differ based on transplant indication. Methods: In this case control study of children who underwent HCT at our institution, we evaluated the clinical and transplant characteristics of subjects who developed AICs compared to a control group matched by transplant indication and donor type. In cases, we analyzed the state of immune reconstitution, including B cell recovery, T cell recovery, and chimerism, immediately prior to AIC onset. Subjects were stratified by primary indication for transplant as malignancy (n = 7), primary immune deficiency (PID, n = 9) or other non-malignant disease (n = 4). We then described the treatment and outcomes for 20 subjects who developed AICs. Results: In our cohort, cases were older than controls, were more likely to receive a myeloablative conditioning regimen and had a significantly lower prevalence of chronic GVHD. There were distinct differences in the state of immune recovery based on transplant indication. None of the patients (0/7) transplanted for primary malignancy had T cell recovery at AIC onset compared to 71% (5/7) of patients with PID and 33% (1/3) of patients with non-malignant disease. The subset of patients with PID and non-malignant disease who achieved T cell reconstitution (6/6) prior to AIC onset, all demonstrated mixed or split chimerism. Subjects with AIHA or multi-lineage cytopenias had particularly refractory courses with poor treatment response to IVIG, steroids, and rituximab. Conclusions: These results highlight the heterogeneity of AICs in this population and suggest that multiple mechanisms may contribute to the development of post-transplant AICs. Patients with full donor chimerism may have early B cell recovery without proper T cell regulation, while patients with mixed or split donor chimerism may have residual host B or plasma cells making antibodies against donor blood cells. A prospective, multi-center trial is needed to develop personalized treatment approaches that target the immune dysregulation present and improve outcomes in patients with post-transplant AICs.

During the austral summer of 2016-17, the third-generation camera, SPT-3G, was installed on the South Pole Telescope, increasing the detector count in the focal plane by an order of magnitude relative to the previous generation. Designed to map the polarization of the cosmic microwave background, SPT-3G contains ten 6-in-hexagonal modules of detectors, each with 269 trichroic and dual-polarization pixels, read out using 68x frequency-domain multiplexing. Here we discuss design, assembly, and layout of the modules, as well as early performance characterization of the first-year array, including yield and detector properties., Conference proceeding for Low Temperature Detectors 2017. Accepted for publication: 27 August 2018

Plasmon in two-dimensional electron gas (2DEG) has long been considered as a promising active medium for terahertz emitters and detectors. However, the efficiency of terahertz plasmonic devices is severely limited by the high damping rate of plasma wave in solid state. In addition to the enhancement of plasmon lifetime by using 2DEGs with higher carrier mobility, engineering on the boundary condition and electromagnetic environment of plasmon cavity helps to preserve the plasmon states. Here we report on terahertz reflection spectroscopy of plasmon states in a grating-coupled AlGaN/GaN-2DEG plasmonic device at 7 K in equilibrium with ambient blackbody irradiation. Localized plasmon states and plasmon-polariton states were observed when the core plasmonic device is integrated with a silicon lens and when it is embedded in a terahertz Fabry-Perot cavity, respectively. Simulation results including the reflection spectra and total reflection power agree well with the measured results. The Rabi splitting is found to be inversely proportional to the resonance frequency, and follows a linear relation with the square root of the sheet electron density. A normalized coupling ratio, ΩRω0≈0.13, is achieved between the Rabi splitting ΩR and the resonance frequency ω0. The coupling ratio could be further increased to allow for ultrastrong coupling between terahertz photons and plasmons.

We present two prescriptions for broadband (~77 - 252 GHz), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements, in our case 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially-available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves (97 +/- 2)% transmittance and the lenslet coating sample achieves (94 +/- 3)% transmittance., Comment: 19 pages, 11 figures; submitted 05 Dec 2019, accepted 26 Feb 2020

On behalf of the Clinical Care Consortium for Telomere-associated Ailments (CCCTAA)., Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.

We have developed superconducting Ti transition-edge sensors with Au protection layers on the top and bottom for the South Pole Telescope’s third-generation receiver (a cosmic microwave background polarimeter, due to be upgraded this austral summer of 2017/2018). The base Au layer (deposited on a thin Ti glue layer) isolates the Ti from any substrate effects; the top Au layer protects the Ti from oxidation during processing and subsequent use of the sensors. We control the transition temperature and normal resistance of the sensors by varying the sensor width and the relative thicknesses of the Ti and Au layers. The transition temperature is roughly six times more sensitive to the thickness of the base Au layer than to that of the top Au layer. The normal resistance is inversely proportional to sensor width for any given film configuration. For widths greater than five micrometers, the critical temperature is independent of width.

Purpose Mouse orthotopic single lung transplantation (LTx) is a useful scientific model to explore LTx immunology. C57BL/10 (B10, H-2b) to C57BL/6 (B6, H-2b) minor alloantigen-mismatched LTx exhibits mild acute rejection and sometimes chronic fibrosis, mimicking human LTx where alloimmunity is dampened by immunosuppressants. We have observed variations in allograft histology across experiments, which were not explained by animal vendor or experimental conditions. The purpose of this study was to evaluate those variations objectively. Methods We performed a retrospective review of B10 to B6 LTx performed in our lab and sacrificed 28 days after LTx. LTx with an experimental intervention (e.g., usage of immunomodulatory agents or knock-out mice) were excluded. Surgeons 1 and 2 had had previous rodent LTx experience whereas Surgeons 3-5 had not. Each surgeon's first 10, middle 10, and last 10 LTx in our lab were pathologically graded in a blinded manner. Nonparametric Spearman correlation was computed to compare chronological variation across surgeons. Inter-surgeon differences were compared using two-way ANOVA. Results Data from 143 LTx were available from five surgeons’ records. Surgeon 1’s and 2’s pathology scores were mostly stable throughout the period (e.g. for B-grade rejection, Surgeon 1 r=0.10 and p=0.60, Surgeon 2 r=-0.11 and p=0.55), whereas those of surgeons 3-5 changed over time (e.g. for B-grade rejection, Surgeon 4 r=-0.57 and p Conclusion Mouse single LTx is a powerful model to study the underlying mechanisms of LTx biology. However, the surgeon- and experience-dependent variability in histopathological findings need to be taken into account when designing experimental protocols, particularly when the model has recently been acquired by the surgeon.

Aiming to the performance degradation of the object detection algorithms in low-light environment, the image fusion module (MSRCR-IF) proposed in this paper is introduced into the object detection network based on the object detection algorithm of Mask R-CNN. This proposed fusion algorithm adjusts Region Proposal Network (RPN) and delete instance mask branch to achieve better pedestrian detection performance of algorithm in low-light environment. The experimental results reveal that the algorithm proposed in this paper has better detection performance than other current mainstream algorithms in COCO2017 data set, and the average detection accuracy of 85.05% was achieved under the self-built low-light road environment data set, which was 4.66% higher than before improvement. In order to verify the effectiveness of the improved algorithm, a real car data test was conducted, and the test results showed that the improved method can effectively improve the detection effect of pedestrians in low light conditions.

The health home program established under the Affordable Care Act (2010) is derived from the medical home concept originated by the American Academy of Pediatrics in 1968 to provide a care delivery model for children with special health care needs. As applied to behavioral health, health homes or medical homes have become increasingly adult-focused models, with a primary goal of coordinating physical and behavioral health care. For children and youth with serious emotional disorders, health homes must go beyond physical and behavioral health care to connect with other child-focused sectors, such as education, child welfare, and juvenile justice. Each of these systems have a significant role in helping children meet health and developmental goals, and should be included in integrated approaches to care for children and youth. Health homes for young people should incorporate a continuum of care from health promotion to the prevention and treatment of disorders. The challenge for child- and youth-focused health homes is to integrate effective services and supports into the settings where young people naturally exist, drawing on the best evidence from mental health, physical medicine, and other fields. What may be needed is not a health home as currently conceptualized for adults, nor a traditional medical home, but a family- and child-centered coordinated care and support delivery system supported by health homes or other arrangements. This article sets out a health home framework for children and youth with serious mental health conditions and their families, examining infrastructure and service delivery issues.