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

Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration

Macroautophagy/autophagy, a defense mechanism against aberrant stresses, in neurons counteracts aggregate-prone misfolded protein toxicity. Autophagy induction might be beneficial in neurodegenerative diseases (NDs). The natural compound trehalose promotes autophagy via TFEB (transcription factor EB), ameliorating disease phenotype in multiple ND models, but its mechanism is still obscure. We demonstrated that trehalose regulates autophagy by inducing rapid and transient lysosomal enlargement and membrane permeabilization (LMP). This effect correlated with the calcium-dependent phosphatase PPP3/calcineurin activation, TFEB dephosphorylation and nuclear translocation. Trehalose upregulated genes for the TFEB target and regulator Ppargc1a, lysosomal hydrolases and membrane proteins (Ctsb, Gla, Lamp2a, Mcoln1, Tpp1) and several autophagy-related components (Becn1, Atg10, Atg12, Sqstm1/p62, Map1lc3b, Hspb8 and Bag3) mostly in a PPP3- and TFEB-dependent manner. TFEB silencing counteracted the trehalose prodegradative activity on misfolded protein causative of motoneuron diseases. Similar effects were exerted by trehalase-resistant trehalose analogs, melibiose and lactulose. Thus, limited lysosomal damage might induce autophagy, perhaps as a compensatory mechanism, a process that is beneficial to counteract neurodegeneration

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

A prospective cohort study of the impact of outpatient Intensive Cardiac Rehabilitation on depression and cardiac self-efficacy

STUDY OBJECTIVE: To evaluate whether an Intensive Cardiac Rehabilitation (ICR) program improves depression and cardiac self-efficacy among patients with a qualifying cardiac diagnosis. DESIGN: Prospective, longitudinal cohort design. SETTING: Single-center, tertiary referral, outpatient cardiac rehabilitation center. PARTICIPANTS: Patients with a qualifying diagnosis for ICR. INTERVENTIONS: Outpatient ICR. MAIN OUTCOME MEASURES: Mental health, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and cardiac self-efficacy using the Cardiac Self-Efficacy (CSE) scale. RESULTS: Of the 268 patients included (median age 69 y, 73% men), 70% had no depressive symptoms at baseline (PHQ-9 score \u3c5). PHQ-9 scores improved in the overall sample (p \u3c 0.0001), with greater improvements among patients with mild depressive symptoms at baseline (-4 points, p \u3c 0.001) and those with moderate to severe depressive symptoms at baseline (-5.5 points, p \u3c 0.001). Cardiac self-efficacy improved overall, and the two subsections of the cardiac self-efficacy questionnaire titled, maintain function and control symptoms improved (all p \u3c 0.001). CONCLUSIONS: Participation in an outpatient ICR program is associated with fewer depressive symptoms and greater cardiac self-efficacy among patients with CVD who qualify for ICR. The improvement in depression was greatest for those with moderate to severe depressive symptoms

STEM education in the twenty-first century: learning at work-an exploration of design and technology teacher perceptions and practices

Teachers’ knowledge of STEM education, their understanding, and pedagogical application of that knowledge is intrinsically linked to the subsequent effectiveness of STEM delivery within their own practice; where a teacher’s knowledge and understanding is deficient, the potential for pupil learning is ineffective and limited. Set within the context of secondary age phase education in England and Wales (11–16 years old), this paper explores how teachers working within the field of design and technology education acquire new knowledge in STEM; how understanding is developed and subsequently embedded within their practice to support the creation of a diverse STEM-literate society. The purpose being to determine mechanisms by which knowledge acquisition occurs, to reconnoitre potential implications for education and learning at work, including consideration of the role which new technologies play in the development of STEM knowledge within and across contributory STEM subject disciplines. Underpinned by an interpretivist ontology, work presented here builds upon the premise that design and technology is an interdisciplinary educational construct and not viewed as being of equal status to other STEM disciplines including maths and science. Drawing upon the philosophical field of symbolic interactionism and constructivist grounded theory, work embraces an abductive methodology where participants are encouraged to relate design and technology within the context of STEM education. Emergent findings are discussed in relation to their potential to support teachers’ educational development for the advancement of STEM literacy, and help secure design and technology’s place as a subject of value within a twenty-first Century curriculum

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