Battery Health Quantification for TDRS Spacecraft by Using Signature Discriminability Measurement

The NASA/GSFC Space Network Project Office (SN) currently operates a constellation of ten geosynchronous TDRS spacecraft launched over the past 30 years. The SN project collects up to 16.5 Gigabytes of telemetry every month. Generally, the spacecraft health and functionality are obtained by the use of real-time telemetry data for the multiple spacecraft subsystems, which are transmitted to the main ground station at the White Sands Complex in Las Cruces, NM. Recently, the SN has instituted a program of Big Data to analyze the large amounts of data using a variety of tools including Machine Learning, Artificial Intelligence, development of training sets, and a variety of mathematical modeling tools. The goal is to improve spacecraft management and obtain a more accurate prediction of the spacecraft end of life. The combination of these efforts with those of the Aerospace Corporation, which has a contract with the SN to produce yearly reliability estimates for the TDRS fleet, will be performed. This paper presents a new concept called telemetry quality quantification (TQQ) and discusses the progress that has been made in battery performance estimation for the second-generation TDRS spacecraft using a signature discriminability measures (SDM) algorithm combined with the Aerospace Corp. battery life estimation models. This activity is important because many of the TDRS fleet of spacecraft have exceeded their on-orbit design lifetime and, therefore, NASA must carefully manage the spacecraft to continue operations while avoiding an end-of-mission scenario that leaves a non-functioning spacecraft in geosynchronous orbit

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Data from: Manipulating wetland hydroperiod to improve occupancy rates by an endangered amphibian: modelling management scenarios

Environmental managers have the difficult task of ensuring species persistence despite considerable uncertainty about their response to management. Spatially explicit population models provide one solution for simulating the dynamics of species and evaluating alternative management regimes. We used a Bayesian model to investigate wetland occupancy dynamics of the endangered growling grass frog Litoria raniformis at a wastewater treatment plant in southern Victoria, Australia. We coupled prior information from earlier research on this species with our survey data to quantify the effects of patch-scale variables and connectivity on the probabilities of occupancy, population extinction and colonization. Hydroperiods of 13 sites were experimentally enhanced to bolster occupancy rates by L. raniformis. We used simulations to assess the extent to which the enhanced hydroperiod regime improved the viability of the focal metapopulation. Occupancy rate increased by 15% among the enhanced sites in 2013–2014, whereas the rate of occupancy among unenhanced sites fell by 11% in that year. Forward simulation using the dynamic occupancy model suggested that the minimum occupancy rate across the metapopulation would be 18% higher if the enhanced hydroperiod regime was retained over the next 20 years. Mean posterior effects of patch-scale variables and connectivity on the occupancy dynamics of L. raniformis were consistent with the prior effect in all cases, with only small changes to the size of these effects. There was no clear effect of water chemistry on occupancy dynamics. Synthesis and applications. This work suggests that managing the hydroperiod of constructed wetlands can be an effective tool for the conservation of amphibians and demonstrates the utility of spatially explicit models for assessing metapopulation viability. We encourage managers to experimentally test the efficacy of manipulating patch-scale variables to improve occupancy rates within amphibian metapopulations

Hamer et al_2016_JAPPL_water quality

This file contains OpenBUGS code for deriving estimates of initial site occupancy, local colonisation and extinction, number of occupied sites and metapopulation growth rate from a model of Water Quality. Parameters included are effective wetland area (effarea), mean cover of aquatic vegetation (aqveg), connectivity (conn), turbidity (turb) and electrical conductivity (cond)

Hamer et al_2016_JAPPL_base model

This file contains OpenBUGS code for deriving estimates of initial site occupancy, local colonisation and extinction, number of occupied sites and metapopulation growth rate from a Base model. Parameters included are effective wetland area (effarea), mean cover of aquatic vegetation (aqveg) and connectivity (conn)

Hamer et al_2016_JAPPLE_Habitat&Detection_Data

This file contains data on effective wetland area and mean proportion cover of aquatic vegetation at 33 sites sampled in each of four years. The water chemistry parameters electrical conductivity (EC, log transformed) and turbidity (ntu) are provided as a mean over the four years of sampling. A detection matrix is provided that contains a '1' whenever Litoria raniformis was detected during a survey. 'NA' denotes that a survey was not conducted at that time. A distance matrix includes edge-to-edge distances (metres) between all 33 sites

Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein–methyltransferase superfamily

The retinoblastoma protein-interacting zinc finger gene RIZ (PRDM2) is a member, by sequence homology, of a nuclear protein–methyltransferase (MTase) superfamily involved in chromatin-mediated gene expression. The gene produces two protein products, RIZ1 that contains a conserved MTase domain and RIZ2 that lacks the domain. RIZ1 gene expression is frequently silenced in human cancers, and the gene is also a common target of frameshift mutation in microsatellite-unstable cancers. We now report studies of mice with a targeted mutation in the RIZ1 locus. The mutation inactivates RIZ1 but not RIZ2. These RIZ1 mutant mice were viable and fertile but showed a high incidence of diffuse large B-cell lymphomas (DLBL) and a broad spectrum of unusual tumors. RIZ1 deficiency also accelerated tumorigenesis in p53 heterozygous mutant mice. Finally, several missense mutations of RIZ1 were found in human tumor tissues and cell lines; one of these was particularly common in human DLBL tumors. These missense mutations, as well as the previously described frameshift mutation, all mapped to the MTase functional domains. All abolished the capacity of RIZ1 to enhance estrogen receptor activation of transcription. These data suggest a direct link between tumor formation and the MTase domain of RIZ1 and describe for the first time a tumor susceptibility gene among methyltransferases