Synthesis and alkyne-coupling chemistry of cyclomanganated 1- and 3-acetylindoles, 3-formylindole and analogues

The syntheses are reported of new cyclomanganated indole derivatives (1-acetyl-κO-indolyl-κC2)dicarbonylbis(trimethylphosphite)manganese (2), (1-methyl-3-acetyl-κO-indolyl-κC2)tetracarbonylmanganese (4), (3-formyl-κO-indolyl-κC2)tetracarbonylmanganese (5a) and (1-methyl-3-formyl-κO-indolyl-κC2)tetracarbonylmanganese (5b). The unusually complicated crystal structure of 5b has been determined, the first for a cyclomanganated aryl aldehyde. The preparations of a mitomycin-related pyrrolo-indole and related products by thermally promoted and oxidatively (Me3NO) initiated alkyne-coupling reactions of the previously known complex (1-acetyl-κO-indolyl-κC2)tetracarbonylmanganese (1) are reported for different alkynes and solvents. X-ray crystal structures are reported for the dimethyl acetylenedicarboxylate coupling product of 1 (dimethyl 1-methyl-l-hydroxypyrrolo[1,2a]-indole-2,3-dicarboxylate; 6a), and an unusually-cyclised triple insertion product 8 from the coupling of acetylene with 4, in which a cyclopentadiene moiety is η3-allyl-coordinated to Mn through only one double bond and an exocyclic carbon, but which rearranges on heating to an η5-cyclopentadienyl complex

Socioeconomic status, obesity and lifestyle in men : the Geelong Osteoporosis Study

Background : Although the association between lower socioeconomic status (SES) and obesity in women in developed countries is well-documented, current evidence regarding the relationship between obesity in men and area-based SES (equivalised for advantage and disadvantage) is inconsistent. Therefore, we aimed to examine obesity, lifestyle behaviours, physical activity in different domains and demographics in men using area-based SES.Methods : We performed a descriptive cross-sectional study of 1467 randomly selected white men (mean age 56 year (inter-quartile range (IQR) = 39&ndash;73 year)) recruited from the Barwon Statistical Division, South Western Victoria, Australia between 2001&ndash;06.Results : Age-adjusted BMI, waist circumference, % fat and lean mass and blood pressure were inversely associated with SES, with differences between low and upper SES (P for difference &lt;0.05), independent of country of birth. Age-adjusted lifestyle behaviours associated with obesity and/or adverse health (especially cardiovascular disease), were also associated with lower SES.Conclusions : Subjects from lower SES had greater measures of obesity despite being more physically active at work, but were less likely to be physically active in the domains of sports and/or leisure. These findings suggest the possible influence of lifestyle behaviours and occupation upon obesity in men and should be investigated further.<br /

A cultural models approach to osteoporosis prevention and treatment

This article identifies cultural models of osteoporosis, as shared by community-dwelling older women in southeastern Australia, and compares these with cultural knowledge conveyed through social marketing. Cultural models are mental constructs about specific domains in everyday life, such as health and illness, which are shared within a community. We applied domain analyses to data obtained from in-depth interviews and stakeholder-identified print materials. The response domains identified from our case studies made up the shared cultural model &ldquo;Osteoporosis has low salience,&rdquo; particularly when ranked against other threats to health. The cultural knowledge reflected in the print materials supported a cultural model of low salience. Cultural cues embedded in social marketing messages on osteoporosis may be internalized and motivating in unintended ways. Identifying and understanding cultural models of osteoporosis within a community may provide valuable insights to inform the development of targeted health messages.<br /

Tobacco smoking as a risk factor for major depressive disorder : a population-based study

Background : Smoking is disproportionately prevalent among people with psychiatric illness. Aims : To investigate smoking as a risk factor for major depressive disorder. Method : A population-based sample of women was studied using case&ndash;control and retrospective cohort study designs. Exposure to smoking was self-reported, and major depressive disorder diagnosed using the Structured Clinical Interview for DSM&ndash;IV&ndash;TR (SCID&ndash;I/NP). Results : Among 165 people with major depressive disorder and 806 controls, smoking was associated with increased odds for major depressive disorder (age-adjusted odds ratio (OR)=1.46, 95% CI 1.03&ndash;2.07). Compared with non-smokers, odds for major depressive disorder more than doubled for heavy smokers (&gt;20 cigarettes/day). Among 671 women with no history of major depressive disorder at baseline, 13 of 87 smokers and 38 of 584 non-smokers developed de novo major depressive disorder during a decade of follow-up. Smoking increased major depressive disorder risk by 93% (hazard ratio (HR)=1.93, 95% CI 1.02&ndash;3.69); this was not explained by physical activity or alcohol consumption. Conclusions : Evidence from cross-sectional and longitudinal data suggests that smoking increases the risk of major depressive disorder in women

Australian Indigenous model of mental healthcare based on transdiagnostic cognitive–behavioural therapy co-designed with the Indigenous community: protocol for a randomised controlled trial

Background A four- to seven-fold increase in the prevalence of current mood, anxiety, substance use and any mental disorders in Indigenous adults compared with non-Indigenous Australians has been reported. A lifetime prevalence of major depressive disorder was 23.9%. High rates of comorbid mental disorders indicated a transdiagnostic approach to treatment might be most appropri- ate. The effectiveness of psychological treatment for Indigenous Australians and adjunct Indigenous spiritual and cultural healing has not previously been evaluated in controlled clinical trials. Aims This project aims to develop, deliver and evaluate the effectiveness of an Indigenous model of mental healthcare (IMMHC). Trial registration: ANZCTR Registration Number: ACTRN12618001746224 and World Health Organization Universal Trial Number: U1111-1222-5849. Method The IMMHC will be based on transdiagnostic cognitive–behav- iour therapy co-designed with the Indigenous community to ensure it is socially and culturally appropriate for Indigenous Australians. The IMMHC will be evaluated in a randomised con- trolled trial with 110 Indigenous adults diagnosed with a current diagnosis of depression. The primary outcome will be the severity of depression symptoms as determined by changes in Beck Depression Inventory-II score at 6 months post-interven- tion. Secondary outcomes include anxiety, substance use disorder and quality of life. Outcomes will be assessed at base- line, 6 months post-intervention and 12 months post- intervention. Results The study design adheres to the Consolidated Standards of Reporting Trials (CONSORT) statement recommendations and CONSORT extensions for pilot trials. We followed the Standard Protocol Items for Randomised Trials statement recommenda- tions in writing the trial protocol. Conclusions This study will likely benefit participants, as well as collaborating Aboriginal Medical Services and health organisations. The transdiagnostic IMMHC has the potential to have a substantial impact on health services delivery in the Indigenous health sector

Common mental disorders among Indigenous people living in regional, remote and metropolitan Australia: a cross-sectional study

Objective: To determine, using face-to-face diagnostic interviews, the prevalence of common mental disorders (CMD) in a cohort of adult Indigenous Australians, the cultural acceptability of the interviews, the rates of comorbid CMD and concordance with psychiatrists’ diagnoses. Design: Cross-sectional study July 2014–November 2016. Psychologists conducted Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision Axis I Disorders (SCID-I) (n=544). Psychiatrists interviewed a subsample (n=78). Setting: Four Aboriginal Medical Services and the general community located in urban, regional and remote areas of Southern Queensland and two Aboriginal Reserves located in New South Wales. Participants: Indigenous Australian adults. Outcome measures: Cultural acceptability of SCID-I interviews, standardised rates of CMD, comorbid CMD and concordance with psychiatrist diagnoses. Results: Participants reported that the SCID-I interviews were generally culturally acceptable. Standardised rates (95% CI) of current mood, anxiety, substance use and any mental disorder were 16.2% (12.2% to 20.2%), 29.2% (24.2% to 34.1%), 12.4% (8.8% to 16.1%) and 42.2% (38.8% to 47.7%), respectively—6.7-fold, 3.8-fold, 6.9- fold and 4.2-fold higher, respectively, than those of the Australian population. Differences between this Indigenous cohort and the Australian population were less marked for 12-month (2.4-fold) and lifetime prevalence (1.3-fold). Comorbid mental disorder was threefold to fourfold higher. In subgroups living on traditional lands in Indigenous reserves and in remote areas, the rate was half that of those living in mainstream communities. Moderate-to- good concordance with psychiatrist diagnoses was found. Conclusions: The prevalence of current CMD in this Indigenous population is substantially higher than previous estimates. The lower relative rates of non-current disorders are consistent with underdiagnosis of previous events. The lower rates among Reserve and remote area residents point to the importance of Indigenous peoples’ connection to their traditional lands and culture, and a potentially important protective factor. A larger study with random sampling is required to determine the population prevalence of CMD in Indigenous Australians

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women

Background: Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population.Methods: In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders.Habitual physical activity,measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded.Results: Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32&ndash;0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association.Conclusion: This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.<br /

Efficacy and safety of oral methazolamide in patients with type 2 diabetes: A 24-week, placebo-controlled, double-blind study

OBJECTIVE To evaluate the safety and efficacy of methazolamide as a potential therapy for type 2 diabetes. RESEARCH DESIGN AND METHODS This double-blind, placebo-controlled study randomized 76 patients to oral methazolamide (40 mg b.i.d.) or placebo for 24 weeks. The primary efficacy end point for methazolamide treatment was a placebo-corrected reduction in HbA1c from baseline after 24 weeks (ΔHbA1c). RESULTS Mean ± SD baseline HbA1c was 7.1 ± 0.7% (54 ± 5 mmol/mol; n = 37) and 7.4 ± 0.6% (57 ± 5 mmol/mol; n = 39) in the methazolamide and placebo groups, respectively. Methazolamide treatment was associated with a ΔHbA1c of –0.39% (95% CI –0.82, 0.04; P < 0.05) (–4.3 mmol/mol [–9.0, 0.4]), an increase in the proportion of patients achieving HbA1c ≤6.5% (48 mmol/mol) from 8 to 33%, a rapid reduction in alanine aminotransferase (∼10 units/L), and weight loss (2%) in metformin-cotreated patients. CONCLUSIONS Methazolamide is the archetype for a new intervention in type 2 diabetes with clinical benefits beyond glucose control

Annual Feedback Is an Effective Tool for a Sustained Increase in Calcium Intake among Older Women

We aimed to optimize calcium intake among the 2,000+ older women taking part in the Vital D study. Calcium supplementation was not included in the study protocol. Our hypothesis was that annual feedback of calcium intake and informing women of strategies to improve calcium intake can lead to a sustained increase in the proportion of women who consume adequate levels of the mineral. Calcium intake was assessed on an annual basis using a validated short food frequency questionnaire (FFQ). Supplemental calcium intake was added to the dietary estimate. Participants and their nominated doctor were sent a letter that the participant’s estimated daily calcium intake was adequate or inadequate based on a cutoff threshold of 800 mg/day. General brief statements outlining the importance of an adequate calcium intake and bone health were included in all letters. At baseline, the median daily consumption of calcium was 980 mg/day and 67 percent of 1,951 participants had calcium intake of at least 800 mg per day. Of the 644 older women advised of an inadequate calcium intake at baseline (<800 mg/day), 386 (60%) had increased their intake by at least 100 mg/day when re-assessed twelve months later. This desirable change was sustained at 24 months after baseline with almost half of these women (303/644) consuming over 800 mg calcium per day. This study devised an efficient method to provide feedback on calcium intake to over 2,000 older women. The improvements were modest but significant and most apparent in those with a low intake at baseline. The decreased proportion of these women with an inadequate intake of calcium 12- and 24-months later, suggests this might be a practical, low cost strategy to maintain an adequate calcium intake among older women

Dynamic Time Warping Averaging of Time Series Allows Faster and More Accurate Classification

Recent years have seen significant progress in improving both the efficiency and effectiveness of time series classification. However, because the best solution is typically the Nearest Neighbor algorithm with the relatively expensive Dynamic Time Warping as the distance measure, successful deployments on resource constrained devices remain elusive. Moreover, the recent explosion of interest in wearable devices, which typically have limited computational resources, has created a growing need for very efficient classification algorithms. A commonly used technique to glean the benefits of the Nearest Neighbor algorithm, without inheriting its undesirable time complexity, is to use the Nearest Centroid algorithm. However, because of the unique properties of (most) time series data, the centroid typically does not resemble any of the instances, an unintuitive and underappreciated fact. In this work we show that we can exploit a recent result to allow meaningful averaging of 'warped' times series, and that this result allows us to create ultra-efficient Nearest 'Centroid' classifiers that are at least as accurate as their more lethargic Nearest Neighbor cousins