A Size Effect on the Fatigue Crack Growth Rate Threshold of Alloy 718

Fatigue crack growth rate (FCGR) tests were conducted on Alloy 718 in the solution annealed and aged condition at room temperature. In each test, the FCGR threshold was measured using the decreasing (Delta)K method. Initial testing was at two facilities, one of which used C(T) specimens with W = 127 mm. Previous data at the other facility had been obtained with specimens with W = 50.8 mm. A comparison of test results at R = 0.1 showed that the threshold for the 127 mm specimen was considerably higher than that of the 50.8 mm specimen. A check showed that this difference was not due to a heat-to-heat or lab-to-lab variation. Additional tests were conducted on specimens with W = 25.4 mm and at other R values. Data for the various specimens is presented along with parameters usually used to describe threshold behavior

NASA Contractor Report: Guidelines for Proof Test Analysis

These Guidelines integrate state-of-the-art Elastic-Plastic Fracture Mechanics (EPFM) and proof test implementation issues into a comprehensive proof test analysis procedure in the form of a Road Map which identifies the types of data, fracture mechanics based parameters, and calculations needed to perform flaw screening and minimum proof load analyses of fracture critical components. Worked examples are presented to illustrate the application of the Road Map to proof test analysis. The state-of-the-art fracture technology employed in these Guidelines is based on the EPFM parameter, J, and a pictorial representation of a J fracture analysis, called the Failure Assessment Diagram (FAD) approach. The recommended fracture technology is validated using finite element J results, and laboratory and hardware fracture test results on the nickel-based superalloy IN-718, the aluminum alloy 2024-T351 1, and ferritic pressure vessel steels. In all cases the laboratory specimens and hardware failed by ductile mechanisms. Advanced proof test analyses involving probability analysis and Multiple Cycle Proof Testing (MCPT) are addressed. Finally, recommendations are provided on to how to account for the effects of the proof test overload on subsequent service fatigue and fracture behaviors

Guidelines for Proof Test Analysis

These guidelines integrate state-of-the-art elastic-plastic fracture mechanics (EPFM) and proof test implementation issues into a comprehensive proof test analysis procedure in the form of a road map which identifies the types of data, fracture mechanics based parameters, and calculations needed to perform flaw screening and minimum proof load analyses of fracture critical components. Worked examples are presented to illustrate the application of the road map to proof test analysis. The state-of-the art fracture technology employed in these guidelines is based on the EPFM parameter, J, and a pictorial representation of a J fracture analysis, called the failure assessment diagram (FAD) approach. The recommended fracture technology is validated using finite element J results, and laboratory and hardware fracture test results on the nickel-based superalloy Inconel 718, the aluminum alloy 2024-T3511, and ferritic pressure vessel steels. In all cases the laboratory specimens and hardware failed by ductile mechanisms. Advanced proof test analyses involving probability analysis and multiple-cycle proof testing (MCPT) are addressed. Finally, recommendations are provided on how to account for the effects of the proof test overload on subsequent service fatigue and fracture behaviors

SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease.

We conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s). Patients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy. Patients with localized germinoma (n 190) received either CSI alone (n 125) or combined therapy (n 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 0.02 vs 0.88 0.04; P .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n 45) had 0.98 0.023 event-free and overall survival. Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. Reduced-dose craniospinal radiation alone is effective in metastatic disease

Defining Potential Therapeutic Targets in Coronavirus Disease 2019: A Cross-Sectional Analysis of a Single-Center Cohort

OBJECTIVES: Multiple mechanisms have been proposed to explain disease severity in coronavirus disease 2019. Therapeutic approaches need to be underpinned by sound biological rationale. We evaluated whether serum levels of a range of proposed coronavirus disease 2019 therapeutic targets discriminated between patients with mild or severe disease. DESIGN: A search of ClinicalTrials.gov identified coronavirus disease 2019 immunological drug targets. We subsequently conducted a retrospective observational cohort study investigating the association of serum biomarkers within the first 5 days of hospital admission relating to putative therapeutic biomarkers with illness severity and outcome. SETTING: University College London, a tertiary academic medical center in the United Kingdom. PATIENTS: Patients admitted to hospital with a diagnosis of coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-six patients were recruited, 44 (51%) with mild disease and 42 (49%) with severe disease. We measured levels of 10 cytokines/signaling proteins related to the most common therapeutic targets (granulocyte-macrophage colony-stimulating factor, interferon-α2a, interferon-β, interferon-γ, interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, interleukin-7, interleukin-8, tumor necrosis factor-α), immunoglobulin G antibodies directed against either coronavirus disease 2019 spike protein or nucleocapsid protein, and neutralization titers of antibodies. Four-hundred seventy-seven randomized trials, including 168 different therapies against 83 different pathways, were identified. Six of the 10 markers (interleukin-6, interleukin-7, interleukin-8, interferon-α2a, interferon-β, interleukin-1 receptor antagonist) discriminated between patients with mild and severe disease, although most were similar or only modestly raised above that seen in healthy volunteers. A similar proportion of patients with mild or severe disease had detectable spike protein or nucleocapsid protein immunoglobulin G antibodies with equivalent levels between groups. Neutralization titers were higher among patients with severe disease. CONCLUSIONS: Some therapeutic and prognostic biomarkers may be useful in identifying coronavirus disease 2019 patients who may benefit from specific immunomodulatory therapies, particularly interleukin-6. However, biomarker absolute values often did not discriminate between patients with mild and severe disease or death, implying that these immunomodulatory treatments may be of limited benefit

Nonprescribed Antimicrobial Drugs in Latino Community, South Carolina

We investigated in a sample of Latinos the practices of antimicrobial drug importation and use of nonprescribed antimicrobial drugs. In interviews conducted with 219 adults, we assessed health beliefs and past and present behaviors consistent with acquiring antimicrobial drugs without a prescription in the United States. Many (30.6%) believed that antimicrobial drugs should be available in the United States without a prescription. Furthermore, 16.4% had transported nonprescribed antimicrobial drugs into the United States, and 19.2% had acquired antimicrobial agents in the United States without a prescription. A stepwise logistic regression analysis showed that the best predictors of having acquired nonprescribed antimicrobial drugs in the United States were beliefs and behavior consistent with limited regulations on such drugs. Many persons within the Latino community self-medicate with antimicrobial drugs obtained without a prescription both inside and outside the United States, which adds to the reservoir of antimicrobial drugs in the United States

Nosocomial or not? A combined epidemiological and genomic investigation to understand hospital-acquired COVID-19 infection on an elderly care ward.

BACKGROUND: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). AIM: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. METHODS: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. FINDINGS: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). CONCLUSION: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs.S.R. and A.B. are part-funded from Research England’s Expanding Excellence in England (E3) Fund. The sequencing costs were funded by the COVID-19 Genomics UK (COG-UK) Consortium which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute for Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript