The Politics of Extravagance: The Aircraft Nuclear Propulsion Project

The Navy was the post-World War II leader in supporting research for technological innovations intended to strengthen U.S. military might; the ANP project, however, is one instance in which it would have been better not to have been involved at all

State of professionalism in internal auditing

The professional status of internal auditing is an important issue. Internal Auditing must possess the status of a genuine profession in order to attain the requisite authority to enforce its standards on practice. Until this status is attained, commercial compliance with internal auditing standards will be largely voluntary. A field of work that must rely on voluntary compliance with its standards lacks the genuine status possessed by the well established professions such as medicine, law, architecture, and public accounting. This study examines, from a historical perspective, the professional progress made by the field of internal auditing since 1977. The overriding objectives of this examination are: (1) to determine if the field of internal auditing has achieved professional status; (2) to assess whether progress has been made in enhancing the professional status of internal auditing since 1977; and (3) to suggest any actions disclosed by the analysis that might be taken by the field of internal auditing in the future to further enhance its professional status or the prospects thereof

Meta-analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease, as penetrance (proportion of G+ who develop disease) is variable, age-dependent, and not reliably predicted. METHODS: A systematic search of the literature was performed. We employed random effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere genes in two different contexts: clinically-based studies on patients and families with HCM versus population/community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up. FINDINGS: 455 full text manuscripts were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in non-proband relatives carrying P/LP variants identified during cascade screening was 57% (95% confidence interval [CI] [52,63]) and the mean age of HCM diagnosis was 38 years (95% CI [36, 40]). Penetrance varied from ~32% for myosin light chain (MYL3) to ~55% for myosin binding protein C (MYBPC3), ~60% troponin T (TNNT2) and troponin I (TNNI3), and ~65% for myosin heavy chain (MYH7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population, but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower; approximatively 11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ~8 years of follow up, starting from a mean age of ~16 years. However, short-term gene-specific phenotypic conversion varied between ~12% for MYBPC3 to ~23% for MYH7. CONCLUSIONS: The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve understanding of true lifetime penetrance in families and in the community, and to identify drivers of the transition from subclinical to overt HCM

The predictable instability of psychological distress in college students: A comment on Flett, Vredenburg, and Krames

Flett, Vredenburg, and Krames (1995) claim that their data support the view that the apparent instability in distress among college students is artifactual. However, they have merely demonstrated that distress among college students is an unstable phenomena. Their argument that changes in distress scores have statistical rather than substantive explanations erroneously assumes that instability in distress scores is equivalent to error of measurement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44791/1/10862_2005_Article_BF02229116.pd

Evaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patients

Background&nbsp; In order to grow the potential therapeutic armamentarium in the cachexia domain of supportive oncology, there is a pressing need to develop suitable biomarkers and potential drug targets. This pilot study evaluated several potential candidate biomarkers in skeletal muscle biopsies from a cohort of upper gastrointestinal cancer (UGIC) patients.&nbsp; Methods&nbsp; One hundred seven patients (15 weight-stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight-loss of UGIC patients was 8.1 (9.3\%). Cachexia was defined as weight-loss &ge;5\%. Rectus&thinsp;abdominis muscle was obtained at surgery and was analysed by western blotting or quantitative real-time&ndash;polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt, n&thinsp;=&thinsp;52), forkhead box O transcription factors (n&thinsp;=&thinsp;59), ubiquitin E3 ligases (n&thinsp;=&thinsp;59, control of muscle anabolism/catabolism), BNIP3 and GABARAPL1 (n&thinsp;=&thinsp;59, as markers of autophagy), myosin heavy-chain (MyHC, n&thinsp;=&thinsp;54), dystrophin (n&thinsp;=&thinsp;39), &beta;-dystroglycan (n&thinsp;=&thinsp;52), and &beta;-sarcoglycan (n&thinsp;=&thinsp;52, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255&thinsp;days (range 581&ndash;1955&thinsp;days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non-cachectic cancer patients; and (iii) cancer patients surviving &le;1 vs. {\textgreater}1&thinsp;year post operatively.&nbsp; Results&nbsp; Cancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17), P&thinsp;=&thinsp;0.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P&thinsp;=&thinsp;0.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57), P&thinsp;=&thinsp;0.024]. &beta;-Dystroglycan levels were higher in cachectic compared with non-cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20), P&thinsp;=&thinsp;0.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326&thinsp;days, P&thinsp;=&thinsp;0.023) and dystrophin levels (median 341 vs. 660&thinsp;days, P&thinsp;=&thinsp;0.008).&nbsp; Conclusions&nbsp; The present study has identified intramuscular protein level of &beta;-dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers

Girls\u27 perception of physical environmental factors and transportation: reliability and association with physical activity and active transport to school

Background Preliminary evidence suggests that the physical environment and transportation are associated with youth physical activity levels. Only a few studies have examined the association of physical environmental factors on walking and bicycling to school. Therefore, the purpose of this study was (1) to examine the test-retest reliability of a survey designed for youth to assess perceptions of physical environmental factors (e.g. safety, aesthetics, facilities near the home) and transportation, and (2) to describe the associations of these perceptions with both physical activity and active transport to school. Methods Test and retest surveys, administered a median of 12 days later, were conducted with 480 sixth- and eighth-grade girls in or near six U.S. communities. The instrument consisted of 24 questions on safety and aesthetics of the perceived environment and transportation and related facilities. Additionally, girls were asked if they were aware of 14 different recreational facilities offering structured and unstructured activities, and if so, whether they would visit these facilities and the ease with which they could access them. Test-retest reliability was determined using kappa coefficients, overall and separately by grade. Associations with physical activity and active transport to school were examined using mixed model logistic regression (n = 610), adjusting for grade, race/ethnicity, and site. Results Item-specific reliabilities for questions assessing perceived safety and aesthetics of the neighborhood ranged from 0.31 to 0.52. Reliabilities of items assessing awareness of and interest in going to the 14 recreational facilities ranged from 0.47 to 0.64. Reliabilities of items assessing transportation ranged from 0.34 to 0.58. Some items on girls\u27 perceptions of perceived safety, aesthetics of the environment, facilities, and transportation were important correlates of physical activity and, in some cases, active transport to school. Conclusion This study provides some psychometric support for the use of the questionnaire on physical environmental factors and transportation for studying physical activity and active transport to school among adolescent girls. Further work can continue to improve reliability of these self-report items and examine their association of these factors with objectively measured physical activity

‘Tackling’ rugby safety through a collective approach

Commitment to seeking an evidence-informed approachWhen it comes to player welfare, Rugby Union governing bodies have committed to seeking and funding an evidence-informed approach. This involves using research to make informed decisions about policy, laws and injury prevention programmes. Over the last decade, a growing body of research has informed player safety, for example, modifications to scrum laws to reduce catastrophic head and neck injuries.1 However, major gaps remain, including tackle research focusing on the women’s game.2A socioecological perspectiveIt is well understood that player welfare, specifically injury prevention, is a complex issue. To effectively address these complexities and make a long-term impact requires a dynamic socioecological approach.3 ,4 An athlete operates within a socioecological structure (individual, interpersonal, organisational, community) that is influenced by a web of inter-related factors and actors, both of which change over time and/or when a factor/actor is modified (figure 1). Typically, injury prevention research will identify player level factors that influence injury risk (risk factors), and aim to modify these factors through behaviour change interventions. However, the socioecological view emphasises understanding contextual factors influencing implementation of such modifications. For example, if the behaviour intervention is a training programme, how much time is available to implement the training programme? Or, is the training programme appropriate for all sexes