On the Conditional and Unconditional Type I Error Rates and Power of Tests in Linear Models with Heteroscedastic Errors

Preliminary tests for homoscedasticity may be unnecessary in general linear models. Based on Monte Carlo simulations, results suggest that when testing for differences between independent slopes, the unconditional use of weighted least squares regression and HC4 regression performed the best across a wide range of conditions

Mesoscale Hydrographic Variability in the Vicinity of Points Conception and Arguello During April May 1983: The OPUS 1983 Experiment

In April and May 1983, interdisciplinary oceanographic observations were made of upwelling events in the Point Conception area off southern California. The principal objective was to observe the structure and time dependence of the upwelling system. To accomplish this, two ships, two aircraft, moorings, drogues, and satellite imagery were all included in the observational effort. During the intensive measurement period three main upwelling events and two intervening relaxation or downwelling intervals were sampled during what was a period of overall longer-term sea surface warming. Surface temperatures during upwelling were as low as 10.5°C in the upwelling center between Point Arguello and Point Conception, while during periods of nonupwelling winds, temperatures reached 14°–15°C in the same area. The upwelling center was also a source of higher-salinity water (33.7‰) relative to the offshore waters that were anomalously fresh (33.3‰). Upwelling was observed off Point Arguello, Point Conception, and the area between with a possible lag of up to a day at Point Conception relative to the other areas. The upwelling plume as observed by surface mapping and remote sensing tended to move in a variety of directions from SE to SW. Part of the movement was usually into the Santa Barbara Channel, but other parts of the plume occasionally moved southwestward. There was no obvious correlation of plume direction with the wind. During relaxation events the entire region was covered by a 10- to 20-m-thick warm (14°–16°C), fresh

Organization of persistent upwelling structures : hydrographic observations, 5 April-10 May 1983. Vol. 2

The area near Point Arguello has long been recognized as a location of strong upwelling. A tongue of biologically active waters was observed in the earliest studies of this region (Sverdrup and Allen, 1939). More recently, satellite estimates of chlorophyll by the Coastal Zone Color Scanner (CZCS) on Nimbus-7 have shown the presence of this tongue emanating from Point Arguello in nearly all images off southern California (e.g., Smith and Baker, 1982; Atkinson et al., 1986). This feature is apparently not unique to the Point Arguello region. Similar structures are evident from CZCS and infra-red images near other major points and capes along the west coast of North America (e.g., Abbott and Zion, 1985). Along the central and southern California coast, the tongue off Point Arguello is the largest in spatial extent and the most persistent. The Organization of Persistent Upwelling Structures (OPUS) program was developed with the goal of understanding the relationship between the circulation and planktonic processes in this upwelling region extending southward from Point Arguello. After a small OPUS pilot study in spring 1981 (see Brink et al., 1984, for a summary) a modest program, OPUS-83 (see Atkinson et al., 1986), was funded by the National Science Foundation with the specific objectives of 1) characterizing the physical and biological oceanographic setting in the region within roughly 40 km of Point Arguello; 2) examining the dynamical features of upwelling in this region; 3) obtaining design information for a possible major future OPUS field effort; and 4) achieving some preliminary understanding of the ecosystem dynamics in this region. The field work for OPUS-83 was completed in April and May 1983. This particular time period was selected in order to observe the physical and biological variability during the first few days after the seasonal transition from weak to strong upwelling, the so-called "spring transition" (e.g., Huyer et al., 1979; Brink et al., 1984; Strub et al., 1987; Lentz, 1987). Fortuitously, the OPUS-83 field study was also conducted during a very unusual warming event in the California Current (Simpson, 1983). The sea surface temperatures observed along the California coast during winter and spring of 1983 were the highest recorded since 1958-59. This 1983 warming was related to the major El Nino occurrence in the tropical Pacific Ocean. OPUS-83 was an interdisciplinary program which included physical, chemical and biological measurements repeated at regular intervals on a fixed sampling grid. The hydrographic observations (CTD and XBT) are summarized in two data reports. This report is Volume 2 which contains vertical sections and horizontal maps at selected depths of temperature, salinity and σt Volume 1 contains a detailed background and summary of the OPUS program and vertical profiles of temperature, salinity and σt The text from the sampling, data calibration and processing, and data presentation sections of Volume 1 are included here for easy reference.V. 1. Vertical profiles -- v. 2. Maps and vertical section

Validity and Reliability of the US National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Symptomatic adverse events (AEs) in cancer trials are currently reported by clinicians using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). To integrate the patient perspective, the NCI developed a patient-reported outcomes version of the CTCAE (PRO-CTCAE) to capture symptomatic AEs directly from patients

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p