Diffusion bonding of IN 718 to VM 350 grade maraging steel

Diffusion bonding studies have been conducted on IN 718, VM 350 and the dissimilar alloy couple, IN 718 to maraging steel. The experimental processing parameters critical to obtaining consistently good diffusion bonds between IN 718 and VM 350 were determined. Interrelationships between temperature, pressure and surface preparation were explored for short bending intervals under vacuum conditions. Successful joining was achieved for a range of bonding cycle temperatures, pressures and surface preparations. The strength of the weaker parent material was used as a criterion for a successful tensile test of the heat treated bond. Studies of VM-350/VM-350 couples in the as-bonded condition showed a greater yielding and failure outside the bond region

A theory-based approach to understanding condom errors and problems reported by men attending an STI clinic

The official published version can be accessed from the link below - Copyright @ 2008 Springer VerlagWe employed the information–motivation–behavioral skills (IMB) model to guide an investigation of correlates for correct condom use among 278 adult (18–35 years old) male clients attending a sexually transmitted infection (STI) clinic. An anonymous questionnaire aided by a CD-recording of the questions was administered. Linear Structural Relations Program was used to conduct path analyses of the hypothesized IMB model. Parameter estimates showed that while information did not directly affect behavioral skills, it did have a direct (negative) effect on condom use errors. Motivation had a significant direct (positive) effect on behavioral skills and a significant indirect (positive) effect on condom use errors through behavioral skills. Behavioral skills had a direct (negative) effect on condom use errors. Among men attending a public STI clinic, these findings suggest brief, clinic-based, safer sex programs for men who have sex with women should incorporate activities to convey correct condom use information, instill motivation to use condoms correctly, and directly enhance men’s behavioral skills for correct use of condoms

The effects on clinical trial activity of direct funding and taxation policy interventions made by government: A systematic review

Context Governments have attempted to increase clinical trial activity in their jurisdictions using a range of methods including targeted direct funding and industry tax rebates. The effectiveness of the different approaches employed is unclear. Objective To systematically review the effects of direct government financing interventions by allowing companies to reduce their tax payable on clinical trial activity. Data sources Pub Med, Scopus, Sage, ProQuest, Google Scholar and Google were searched up to the 11th of April 2022. In addition, the reference lists of all potentially eligible documents were hand searched to identify additional reports. Following feedback from co-authors, information on a small number of additional interventions were specifically sought out and included. Data extraction Summary information about potentially eligible reports were reviewed independently by two researchers, followed by extraction of data into a structured spreadsheet for eligible studies. The primary outcomes of interest were the number of clinical trials and the expenditure on clinical trials but data about other evaluations were also collected. Results There were 1694 potentially eligible reports that were reviewed. Full text assessments were done for 304, and 30 reports that provided data on 43 interventions were included- 29 that deployed targeted direct funding and 14 that provided tax rebates or exemptions. There were data describing effects on a primary outcome for 25/41 of the interventions. The most common types of interventions were direct funding to researchers via special granting mechanisms and tax offsets to companies and research organisations. All 25 of the studies for which data were available reported a positive impact on numbers and/or expenditure on clinical trials though the robustness of evaluations was limited for many. Estimates of the magnitude of effects of interventions were reported inconsistently, varied substantially, and could not be synthesised quantitatively, though targeted direct funding interventions appeared to be associated with more immediate impact on clinical trial activity. Conclusion There is a high likelihood that governments can increase clinical trial activity with either direct or indirect fiscal mechanisms. Direct funding may provide a more immediate and tangible return on investment than tax rebates

Small cell lung cancer cell lines secrete predominantly ACTH precursor peptides not ACTH.

A panel of 18 well characterised human small cell lung cancer (SCLC) cell lines was assessed for the production of adrenocorticotrophin (ACTH) and its precursor peptides, pro-opiomelanocortin (POMC) and pro-ACTH. These precursor peptides were measured directly using a novel two-site immunoradiometric assay (IRMA) based on monoclonal antibodies, in conjunction with a similar IRMA for ACTH 1-39. Significant concentrations of ACTH precursors were secreted by 10 of the 18 cell lines (56%). The low levels of ACTH immunoreactivity detected in seven cell lines could be accounted for by the known cross-reactivity of precursors in the ACTH IRMA. This suggests there is little, if any, processing of ACTH precursors to ACTH. Cell pellet extracts contained undetectable or low levels of ACTH precursors and ACTH, indicating that these peptides are not stored intracellularly. During the growth of the SCLC cells in vitro ACTH precursors accumulated progressively in the culture medium. Thus the combination of a direct assay for the ACTH precursors and the panel of SCLC cell lines provides a valuable in vitro model for the expression of POMC in human tumours

Southwest Research Institute assistance to NASA in biomedical areas of the technology utilization program Final report, 1 Nov. 1967 - 30 Nov. 1968

Southwest Research Institute activities in technology utilization program in biomedical areas, Nov. 1967 - Nov. 196

Factors influencing the time to ethics and governance approvals for clinical trials: a retrospective cross-sectional survey

Background: The findings from multi-centre trials are central to the practice of evidence-based medicine, enabling the development and implementation of new treatments. The time it takes to commence clinical trials at sites can be long, and ethics and governance approvals are key steps on the pathway to site activation. The goal of this study was to explore factors influencing the times to ethics approval, governance approval and site activation for multi-centre clinical trials. Methods: This paper assessed the associations of trial characteristics (disease area and trial phase), site characteristics (government or private ownership, country) and characteristics of the ethics and governance processes (scope guidelines, mutual acceptance requirements and triage of projects by risk) with times to approvals and activation. Median times were compared between site initiations that were and were not exposed to each characteristic using non-parametric tests in univariable and multivariable regressions. Results: There were data from 150 site activations done across 91 sites, 16 trials and 5 countries from November 2013 to November 2021. The overall median time to activation was 234 days (range 74 to 657), with ethics approval taking a median of 48 days (0 to 369) and governance approval a median of 34 days (0 to 489). Both the univariable and multivariable analyses identified associations of disease area, particularly oncology (p univariable = 0.012, p multivariable = 0.044), use of scope guidelines (p 0.054). The only factors associated with reduced overall time to site activation in both univariable and multivariable analyses were the early trial phase (p < 0.001, p = 0.013) and mutual acceptance of ethics approvals (p = 0.031, p = 0.030). Interpretation: Times to ethics and governance approvals were only one third of total trial start-up time. Factors influencing times to approval and activation were somewhat inconsistent across analyses, but it seems likely that the introduction of selected governance and ethics processes can reduce approval times

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

Social stress and glucocorticoids alter PERIOD2 rhythmicity in the liver, but not in the suprachiasmatic nucleus

Circadian (~24 h) rhythms in behavior and physiological functions are under control of an endogenous circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN directly drives some of these rhythms or serves as a coordinator of peripheral oscillators residing in other tissues and organs. Disruption of the circadian organization may contribute to disease, including stress-related disorders. Previous research indicates that the master clock in the SCN is resistant to stress, although it is unclear whether stress affects rhythmicity in other tissues, possibly mediated by glucocorticoids, released in stressful situations. In the present study, we examined the effect of uncontrollable social defeat stress and glucocorticoid hormones on the central and peripheral clocks, respectively in the SCN and liver. Transgenic PERIOD2::LUCIFERASE knock-in mice were used to assess the rhythm of the clock protein PERIOD2 (PER2) in SCN slices and liver tissue collected after 10 consecutive days of social defeat stress. The rhythmicity of PER2 expression in the SCN was not affected by stress exposure, whereas in the liver the expression showed a delayed phase in defeated compared to non-defeated control mice. In a second experiment, brain slices and liver samples were collected from transgenic mice and exposed to different doses of corticosterone. Corticosterone did not affect PER2 rhythm of the SCN samples, but caused a phase shift in PER2 expression in liver samples. This study confirms earlier findings that the SCN is resistant to stress and shows that clocks in the liver are affected by social stress, which might be due to the direct influence of glucocorticoids released from the adrenal gland

The State of Self-Organized Criticality of the Sun During the Last 3 Solar Cycles. I. Observations

We analyze the occurrence frequency distributions of peak fluxes $P$, total fluxes $E$, and durations $T$ of solar flares over the last three solar cycles (during 1980--2010) from hard X-ray data of HXRBS/SMM, BATSE/CGRO, and RHESSI. From the synthesized data we find powerlaw slopes with mean values of $\alpha_P=1.72\pm0.08$ for the peak flux, $\alpha_E=1.60\pm0.14$ for the total flux, and $\alpha_T=1.98\pm0.35$ for flare durations. We find a systematic anti-correlation of the powerlaw slope of peak fluxes as a function of the solar cycle, varying with an approximate sinusoidal variation $\alpha_P(t)=\alpha_0+\Delta \alpha \cos{[2\pi (t-t_0)/T_{cycle}]}$, with a mean of $\alpha_0=1.73$, a variation of $\Delta \alpha =0.14$, a solar cycle period $T_{cycle}=12.6$ yrs, and a cycle minimum time $t_0=1984.1$. The powerlaw slope is flattest during the maximum of a solar cycle, which indicates a higher magnetic complexity of the solar corona that leads to an overproportional rate of powerful flares.Comment: subm. to Solar Physic