Establishing Age-calibrated Normative PROMIS Scores for Hand and Upper Extremity Clinic

The purpose of our study is to investigate differences in normative PROMIS upper extremity function (PROMIS-UE), physical function (PROMIS-PF), and pain interference (PROMIS-PI) scores across age cohorts in individuals without upper extremity disability. Methods: Individuals without upper extremity disability were prospectively enrolled. Subjects were administered PROMIS-UE, PROMIS-PF, and PROMIS-PI forms. Retrospective PROMIS data for eligible subjects were also utilized. The enrolled cohort was divided into age groups: 20-39, 40-59, and 60-79 years old. ANOVA, ceiling and floor effect analysis, and kurtosis and skewness statistics were performed to assess PROMIS scores trends with age. Results: This study included 346 individuals. In the 20-39 age group, mean PROMIS scores were 56.2 ± 6.1, 59.8 ± 6.9, and 43.1 ± 6.7 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. In the 40-59 age group, mean PROMIS computer adaptive test scores were 53.3 ± 7.5, 55.3 ± 7.6, and 46.6 ± 7.8 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. In the 60-79 age group, mean PROMIS scores were 48.4 ± 7.6, 48.5 ± 5.6, and 48.7 ± 6.9 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. Differences in mean PROMIS scores were significant across all PROMIS domains and age cohorts (P \u3c 0.001). Conclusion: Younger individuals without hand or upper extremity disability show higher normative PROMIS-UE and PROMIS-PF scores and lower PROMIS-PI scores, indicating greater function and less pain than older counterparts. A universal reference PROMIS score of 50 appears suboptimal for clinical assessment and decision-making in the hand and upper extremity clinic. This study included 346 individuals. In the 20-39 age group, mean PROMIS scores were 56.2 ± 6.1, 59.8 ± 6.9, and 43.1 ± 6.7 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. In the 40-59 age group, mean PROMIS computer adaptive test scores were 53.3 ± 7.5, 55.3 ± 7.6, and 46.6 ± 7.8 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. In the 60-79 age group, mean PROMIS scores were 48.4 ± 7.6, 48.5 ± 5.6, and 48.7 ± 6.9 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. Differences in mean PROMIS scores were significant across all PROMIS domains and age cohorts (P \u3c 0.001)

SMAP L-Band Microwave Radiometer: Instrument Design and First Year on Orbit

The Soil Moisture Active Passive (SMAP) L-band microwave radiometer is a conical scanning instrument designed to measure soil moisture with 4 percent volumetric accuracy at 40-kilometer spatial resolution. SMAP is NASA's first Earth Systematic Mission developed in response to its first Earth science decadal survey. Here, the design is reviewed and the results of its first year on orbit are presented. Unique features of radiometer include a large 6-meter rotating reflector, fully polarimetric radiometer receiver with internal calibration, and radio-frequency interference detection and filtering hardware. The radiometer electronics are thermally controlled to achieve good radiometric stability. Analyses of on-orbit results indicate the electrical and thermal characteristics of the electronics and internal calibration sources are very stable and promote excellent gain stability. Radiometer NEdT (Noise Equivalent differential Temperature) less than 1 degree Kelvin for 17-millisecond samples. The gain spectrum exhibits low noise at frequencies greater than 1 megahertz and 1 divided by f (pink) noise rising at longer time scales fully captured by the internal calibration scheme. Results from sky observations and global swath imagery of all four Stokes antenna temperatures indicate the instrument is operating as expected

A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing.

As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to ∼ 100 × shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.We thank the DKFZ Genomics and Proteomics Core Facility and the OICR Genome Technologies Platform for provision of sequencing services. Financial support was provided by the consortium projects READNA under grant agreement FP7 Health-F4-2008-201418, ESGI under grant agreement 262055, GEUVADIS under grant agreement 261123 of the European Commission Framework Programme 7, ICGC-CLL through the Spanish Ministry of Science and Innovation (MICINN), the Instituto de Salud Carlos III (ISCIII) and the Generalitat de Catalunya. Additional financial support was provided by the PedBrain Tumor Project contributing to the International Cancer Genome Consortium, funded by German Cancer Aid (109252) and by the German Federal Ministry of Education and Research (BMBF, grants #01KU1201A, MedSys #0315416C and NGFNplus #01GS0883; the Ontario Institute for Cancer Research to PCB and JDM through funding provided by the Government of Ontario, Ministry of Research and Innovation; Genome Canada; the Canada Foundation for Innovation and Prostate Cancer Canada with funding from the Movember Foundation (PCB). PCB was also supported by a Terry Fox Research Institute New Investigator Award, a CIHR New Investigator Award and a Genome Canada Large-Scale Applied Project Contract. The Synergie Lyon Cancer platform has received support from the French National Institute of Cancer (INCa) and from the ABS4NGS ANR project (ANR-11-BINF-0001-06). The ICGC RIKEN study was supported partially by RIKEN President’s Fund 2011, and the supercomputing resource for the RIKEN study was provided by the Human Genome Center, University of Tokyo. MDE, LB, AGL and CLA were supported by Cancer Research UK, the University of Cambridge and Hutchison-Whampoa Limited. SD is supported by the Torres Quevedo subprogram (MI CINN) under grant agreement PTQ-12-05391. EH is supported by the Research Council of Norway under grant agreements 221580 and 218241 and by the Norwegian Cancer Society under grant agreement 71220-PR-2006-0433. Very special thanks go to Jennifer Jennings for administrating the activity of the ICGC Verification Working Group and Anna Borrell for administrative support.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1000

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts