Safe Babies, Safe Moms: A Multifaceted, Trauma Informed Care Initiative.

PURPOSE: This report describes a multifaceted, trauma-informed initiative developed to address racial/ethnic maternal and infant health inequities in Washington, D.C. DESCRIPTION: Structural racism and systemic oppression of marginalized communities have played a critical role in maternal and infant health inequities in the United States. Black birthing individuals are exponentially more likely to experience adverse birth outcomes, including preterm birth, low birth weight and maternal mortality. In response to these statistics, the Safe Babies Safe Moms (SBSM) initiative was developed to support patients of marginalized identities and improve health outcomes. SBSM Women's and Infants' Services Specialty Care (WIS-SC) is one component of this initiative focused on perinatal services. ASSESSMENT: SBSM WIS-SC includes trauma-informed clinical services, nurse navigation, lactation, diabetes and nutrition education, social work services, medical-legal services, and behavioral health support. Services are delivered by a multidisciplinary team trained on the following domains: (1) building connection within diverse care teams; (2) recognizing systemic barriers to trauma-informed approaches; (3) learning the brain science of implicit bias, trauma, and resilience; (4) Integrating self-care practices; and (5) acknowledging progress. Since the inception of the program, SBSM WIS-SC has served over 1500 patients. CONCLUSION: The SBSM WIS-SC intervention reflects a patient-centered approach to care, offering the multidisciplinary services required for perinatal patients with complex medical, psychosocial, and legal needs. Trauma informed training and team building is foundational to successful service delivery to address these multifaceted health needs of historically marginalized perinatal populations nationwide.

Pre-hospital ECPR in an Australian metropolitan setting: a single-arm feasibility assessment-The CPR, pre-hospital ECPR and early reperfusion (CHEER3) study.

INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.

Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach.

According to expert consensus, dystonia can be classified as focal, segmental, multifocal, and generalized, based on the affected body distribution. To provide an empirical and data-driven approach to categorizing these distributions, we used a data-driven clustering approach to compare frequency and co-occurrence rates of non-focal dystonia in pre-defined body regions using the Dystonia Coalition (DC) dataset. We analyzed 1,618 participants with isolated non-focal dystonia from the DC database. The analytic approach included construction of frequency tables, variable-wise analysis using hierarchical clustering and independent component analysis (ICA), and case-wise consensus hierarchical clustering to describe associations and clusters for dystonia affecting any combination of eighteen pre-defined body regions. Variable-wise hierarchical clustering demonstrated closest relationships between bilateral upper legs (distance = 0.40), upper and lower face (distance = 0.45), bilateral hands (distance = 0.53), and bilateral feet (distance = 0.53). ICA demonstrated clear grouping for the a) bilateral hands, b) neck, and c) upper and lower face. Case-wise consensus hierarchical clustering at k = 9 identified 3 major clusters. Major clusters consisted primarily of a) cervical dystonia with nearby regions, b) bilateral hand dystonia, and c) cranial dystonia. Our data-driven approach in a large dataset of isolated non-focal dystonia reinforces common segmental patterns in cranial and cervical regions. We observed unexpectedly strong associations between bilateral upper or lower limbs, which suggests that symmetric multifocal patterns may represent a previously underrecognized dystonia subtype.

Accuracy of Emergency Medicine Residents Using Point-of-Care Ultrasound (POCUS) to Detect Retained Stingray Barbs.

BACKGROUND: Stingray envenomation is a common presenting complaint for coastal emergency departments in the United States. Currently, radiograph is the gold standard to evaluate for a retained stingray barb, but ultrasound may be a useful tool to detect retained barbs. OBJECTIVE: To determine if emergency medicine residents could use ultrasound to identify stingray barbs embedded in animal tissue models. A secondary objective was to determine if resident experience affected their ability to detect stingray barbs. METHODS: Thirty-two emergency medicine residents participated in the study. After a short didactic session on foreign body identification with ultrasound, they rotated through six simulation stations and were asked to identify whether a stingray barb was present in pig and chicken tissue models. They were given 2 min per model to identify the presence, size, and depth of a stingray barb. Pre- and postexperiment surveys were collected to assess the residents' level of experience and confidence regarding foreign body identification using ultrasound. RESULTS: Residents accurately identified barbs in chicken drumsticks with a sensitivity of 72.92% (95% confidence interval [CI] 63.89-81.48) and a specificity of 64.58% (95% CI 54.16-74.08), and in pig's feet with a sensitivity of 50.00% (95% CI 39.62-60.38) and specificity of 68.75% (95% CI 58.48-77.82). There was no statistically significant difference regarding accuracy for any outcome measured based on experience or level of training. CONCLUSIONS: The use of point-of-care ultrasound by novice sonographers lacks sensitivity to identify retained stingray barbs in animal models and is not significantly impacted by resident experience with point-of-care ultrasound.

FKBP12 binds to the cardiac ryanodine receptor with negative cooperativity: implications for heart muscle physiology in health and disease.

Cardiac ryanodine receptors (RyR2) release the Ca2+ from intracellular stores that is essential for cardiac myocyte contraction. The ion channel opening is tightly regulated by intracellular factors, including the FK506 binding proteins, FKBP12 and FKBP12.6. The impact of these proteins on RyR2 activity and cardiac contraction is debated, with often apparently contradictory experimental results, particularly for FKBP12. The isoform that regulates RyR2 has generally been considered to be FKBP12.6, despite the fact that FKBP12 is the major isoform associated with RyR2 in some species and is bound in similar proportions to FKBP12.6 in others, including sheep and humans. Here, we show time- and concentration-dependent effects of adding FKBP12 to RyR2 channels that were partly depleted of FKBP12/12.6 during isolation. The added FKBP12 displaced most remaining endogenous FKBP12/12.6. The results suggest that FKBP12 activates RyR2 with high affinity and inhibits RyR2 with lower affinity, consistent with a model of negative cooperativity in FKBP12 binding to each of the four subunits in the RyR tetramer. The easy dissociation of some FKBP12/12.6 could dynamically alter RyR2 activity in response to changes in in vivo regulatory factors, indicating a significant role for FKBP12/12.6 in Ca2+ signalling and cardiac function in healthy and diseased hearts. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Accelerometer-based estimation of oxygen uptake in adults with Down syndrome: vector magnitude vs. vertical axis.

BACKGROUND: Triaxial accelerometer output [vector magnitude (VM) counts] may better estimate physical activity intensity as reflected in the rate of oxygen uptake (V̇O2 ) than the traditional vertical axis (VA) counts in adults with Down syndrome (DS). This study examined the accuracy of VM vs. VA counts in estimating V̇O2 in adults with and without DS across different physical activities and sedentary behaviours. METHODS: Sixteen adults with DS (10 men and 6 women; 31 ± 15 years) and 19 adults without DS (10 men and 9 women; 24 ± 5 years) performed 12 tasks. V̇O2 was measured by portable spirometer (K4b2 , Cosmed) and VM and VA with an accelerometer (wGT3X-BT, Actigraph). RESULTS: Vector magnitude and VA were significant predictors of V̇O2 in adults with DS (P < 0.001; R2  = 0.74 and 0.65, respectively) and adults without DS (P < 0.001; P < 0.001; R2  = 0.75 and 0.61, respectively). Absolute error of prediction was significantly smaller for VM than VA for sitting, playing app, drawing, sweeping, standing and basketball (P ≤ 0.005), but smaller for VA than VM for walking at 0.8 m·s-1 (P = 0.005). Bland-Altman plots for adults with and without DS indicated narrower limits of agreement for VM than VA (-5.57 to 5.57 and -6.44 to 6.44 mL·kg-1 ·min-1 ; -6.21 to 6.17 and -7.75 to 7.74 mL·kg-1 ·min-1 , respectively). CONCLUSIONS: Vector magnitude and VA are significant predictors of V̇O2 in adults with and without DS, yet VM more accurately estimated V̇O2 than VA for most tasks. Development of accelerometer-based prediction of physical activity levels in adults with and without DS may improve by utilising VM counts.

Atmospheric Carbon and Transport - America (ACT-America) Data Sets: Description, Management, and Delivery.

The ACT-America project is a NASA Earth Venture Suborbital-2 mission designed to study the transport and fluxes of greenhouse gases. The open and freely available ACT-America data sets provide airborne in situ measurements of atmospheric carbon dioxide, methane, trace gases, aerosols, clouds, and meteorological properties, airborne remote sensing measurements of aerosol backscatter, atmospheric boundary layer height and columnar content of atmospheric carbon dioxide, tower-based measurements, and modeled atmospheric mole fractions and regional carbon fluxes of greenhouse gases over the Central and Eastern United States. We conducted 121 research flights during five campaigns in four seasons during 2016-2019 over three regions of the US (Mid-Atlantic, Midwest and South) using two NASA research aircraft (B-200 and C-130). We performed three flight patterns (fair weather, frontal crossings, and OCO-2 underflights) and collected more than 1,140 h of airborne measurements via level-leg flights in the atmospheric boundary layer, lower, and upper free troposphere and vertical profiles spanning these altitudes. We also merged various airborne in situ measurements onto a common standard sampling interval, which brings coherence to the data, creates geolocated data products, and makes it much easier for the users to perform holistic analysis of the ACT-America data products. Here, we report on detailed information of data sets collected, the workflow for data sets including storage and processing of the quality controlled and quality assured harmonized observations, and their archival and formatting for users. Finally, we provide some important information on the dissemination of data products including metadata and highlights of applications of ACT-America data sets.

Identifying the 'Achilles heel' of type 1 diabetes.

When Thetis dipped her son Achilles into the River Styx to make him immortal, she held him by the heel, which was not submerged, and thus created a weak spot that proved deadly for Achilles. Millennia later, Achilles heel is part of today's lexicon meaning an area of weakness or a vulnerable spot that causes failure. Also implied is that an Achilles heel is often missed, forgotten or under-appreciated until it is under attack, and then failure is fatal. Paris killed Achilles with an arrow 'guided by the Gods'. Understanding the pathogenesis of type 1 diabetes (T1D) in order to direct therapy for prevention and treatment is a major goal of research into T1D. At the International Congress of the Immunology of Diabetes Society, 2018, five leading experts were asked to present the case for a particular cell/element that could represent 'the Achilles heel of T1D'. These included neutrophils, B cells, CD8+ T cells, regulatory CD4+ T cells, and enteroviruses, all of which have been proposed to play an important role in the pathogenesis of type 1 diabetes. Did a single entity emerge as 'the' Achilles heel of T1D? The arguments are summarized here, to make this case.

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes.

AIMS: Biomarker-driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub-classify iMB, and proffer strategies for personalized, risk-adapted therapies. METHODS: We characterized the iMB molecular landscape, including second-generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). RESULTS: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second-generation subtypes II/III/IV. Subtype II strongly associated with large-cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very-high-risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4 ) and subtype IV tumours were standard risk (80% OS) using upfront CSI-based therapies; randomized-controlled trials of upfront radiation-sparing and/or second-line radiotherapy should be considered. Seventy-five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non-DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH . iMBSHH harboured two distinct subtypes (iMBSHH-I/II ). Within the discriminated favourable-risk iMBSHH DN/MBEN patient group, iMBSHH-II had significantly better progression-free survival than iMBSHH-I , offering opportunities for risk-adapted stratification of upfront therapies. Both iMBSHH-I and iMBSHH-II showed notable rescue rates (56% combined post-relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. CONCLUSIONS: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup-dependent survival models highlight opportunities for biomarker-directed therapies.

Statistical properties of sketching algorithms.

Sketching is a probabilistic data compression technique that has been largely developed by the computer science community. Numerical operations on big datasets can be intolerably slow; sketching algorithms address this issue by generating a smaller surrogate dataset. Typically, inference proceeds on the compressed dataset. Sketching algorithms generally use random projections to compress the original dataset, and this stochastic generation process makes them amenable to statistical analysis. We argue that the sketched data can be modelled as a random sample, thus placing this family of data compression methods firmly within an inferential framework. In particular, we focus on the Gaussian, Hadamard and Clarkson-Woodruff sketches and their use in single-pass sketching algorithms for linear regression with huge samples. We explore the statistical properties of sketched regression algorithms and derive new distributional results for a large class of sketching estimators. A key result is a conditional central limit theorem for data-oblivious sketches. An important finding is that the best choice of sketching algorithm in terms of mean squared error is related to the signal-to-noise ratio in the source dataset. Finally, we demonstrate the theory and the limits of its applicability on two datasets.

Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes.

AIMS: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. METHODS: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). RESULTS: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. CONCLUSIONS: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19-22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6-8 March 2019.

Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs.

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

Fast nonadiabatic dynamics of many-body quantum systems.

Modeling many-body quantum systems with strong interactions is one of the core challenges of modern physics. A range of methods has been developed to approach this task, each with its own idiosyncrasies, approximations, and realm of applicability. However, there remain many problems that are intractable for existing methods. In particular, many approaches face a huge computational barrier when modeling large numbers of coupled electrons and ions at finite temperature. Here, we address this shortfall with a new approach to modeling many-body quantum systems. On the basis of the Bohmian trajectory formalism, our new method treats the full particle dynamics with a considerable increase in computational speed. As a result, we are able to perform large-scale simulations of coupled electron-ion systems without using the adiabatic Born-Oppenheimer approximation.

Bioaerosol detection over Athens, Greece using the laser induced fluorescence technique.

The challenge in today's bioaerosol monitoring is to retrieve real-time information on the qualitative and quantitative composition of the ambient air in bioparticles implicated to human health. A pilot study was conducted during March-May 2018 in Athens, Greece in order to detect bioparticles within the Planetary Boundary Layer (PBL) by implementing the LIF LiDAR (Laser-Induced Fluorescence Light Detection and Ranging) technique at an excitation wavelength of 266 nm in order to determine the major components' contribution on the total fluorescence LiDAR signals aloft (30-100 m above our site). The laboratory characterization of the prevalent pollen grains and fungal spores fluorescence signatures enabled through deconvolution the breaking down of the retrieved LIF LiDAR signals and unravelled each bioparticle's contribution. The bioaerosol occurrence and concentration, as determined by the concurrent sampling with a volumetric particle sampler, verified that the detected fluorescence is related to the fungal and pollen aerosol concentration. The results of this study are very promising for the implementation of remote sensing technology in routine detection and quantification of airborne bioparticles in real-time which is important for allergy sufferers and physicians.