Does diet mediate associations of volume and bouts of sedentary time with cardiometabolic health indicators in adolescents?

Objective: Examine the mediating role of diet in the relationship between volume and duration of sedentary time with cardiometabolic health in adolescents. Methods: Adolescents (12-19 years) participating in the 2003/04 and 2005/06 U.S. National Health and Nutrition Examination Survey (NHANES) were examined. Cardiometabolic health indicators were body mass index z-scores (zBMI) (n 5 1,797) and metabolic syndrome (MetS) (n 5 812). An ActiGraph hip-worn accelerometer was used to derive total sedentary time and usual sedentary bout duration. Dietary intake was assessed using two 24-hour dietary recalls. Mediation analyses were conducted to examine five dietary mediators [total energy intake, discretionary foods, sugar-sweetened beverages (SSB), fruits and vegetables, and dietary quality] of the relationship between total sedentary time and usual sedentary bout duration with zBMI and MetS. Results: Total sedentary time was inversely associated with zBMI (b 5 21.33; 95% CI 22.53 to 20.13) but attenuated after adjusting for moderate-to-vigorous physical activity. No significant associations were observed between usual sedentary bout duration with zBMI or either sedentary measure with MetS. None of the five dietary variables mediated any of the relationships examined. Conclusions: Further studies are needed to explore associations of specific time periods (e.g., after school) and bout durations with both cardiometabolic health indicators and dietary behaviors

Vocabularies of self-determination in 1919: The co-constitution of race and gender in international law

Throughout the twentieth century, the principle of ’self-determination’ had many lives – as political catch-phrase, legal possibility and a justifying logic of world order. In the aftermath of the First World War, it was a principle that suffused the treaty discussions of the Paris peace conference, and loomed large in the framing of the plebiscites, as well as the League of Nations mandate system. This was not least because it animated the claims of numerous nationalist and anti-imperialist activists agitating for increased rights and freedoms in this moment. This chapter explores how the notion of self-determination, and related ideas around national belonging, race and gender, manifested in this 1919 moment in the promises of the Allied leaders, in the claims-making of non-state actors and in the discussions of legal professionals. In so doing it shows how we can understand particular visions of international law in this period as part of a much larger political and cultural conversation about the relationship between the state and national, racial and gendered belonging

Theorizing the history of women's international thinking at the 'end of international theory'

Throughout the 20th century, women were leading intellectuals on International Relations (IR). They thought, wrote, and taught on this subject in numerous political, professional, intimate, and intellectual contexts. They wrote some of the earliest and most powerful theoretical statements of what would later become core approaches to contemporary international theory. Yet, historical women, those working before the late 20th century, are almost completely missing in IR's intellectual and disciplinary histories, including histories of its main theoretical traditions. In this forum, leading historians and theorists of IR respond to the recent findings of the Leverhulme project on Women and the History of International Thought (WHIT), particularly its first two book-length publications on the centrality of women to early IR discourses and subsequent erasure from its history and conceptualization. The forum is introduced by members of the WHIT project. Collectively, the essays suggest the implications of the erasure and recovery of women's international thought are significant and wide-ranging

Evaluation of the 2012 family violence amendments: synthesis report

This report sets out the overall findings of the evaluation of the 2012 family violence amendments. The evaluation examined the effects of amendments to the Family Law Act 1975 (Cth)  that were intended to improve the family law system’s responses to matters involving family violence and safety concerns. Key messages Most separated parents don’t use family dispute resolution, lawyers or courts to resolve parenting matters after they separate Those parents who do use family law systems tend to be those affected by complex issues including family violence, mental ill-health, substance abuse and safety concerns for themselves and/or their children There has been an increased emphasis on identifying families with concerns about family violence and child abuse, however 29% of parents using family law system services reported never being asked about family violence or safety concerns Family law professionals indicated that better screening tools and approaches are required The reforms have supported sorting out parenting arrangements by agreement. This is likely to be due to a change in 2012 that means advisors tell parents that parenting arrangements should be in a child’s best interests Subtle changes in parenting arrangements are evident such as more parents with safety concerns reporting a shift away from overnight stays with fathers The proportion of children with court orders for shared care, where allegations of both family violence or child safety had been raised, fell after the reforms (from 19% to 11%) The proportion of court orders for shared care where neither family violence nor child safety was raised remained stable (22%): no significant change showed where only one issue was raised (17% pre-reform, 15% post-reform). Overall the main findings of the evaluation indicate that the 2012 family violence amendments are a step in the right direction in a reform agenda intended to improve the system’s response to family violence and child abuse concerns in post-separation parenting arrangements. See related content for seperate reports.   &nbsp

Mediating effects of dietary intake on associations of TV viewing, body mass index and metabolic syndrome in adolescents

Objective Evidence suggests that TV viewing is associated with body mass index (BMI) and metabolic syndrome (MetS) in adolescents. However, it is unclear whether dietary intake mediates these relationships. Methods A cross‐sectional analysis was conducted in adolescents (12–19 years) participating in the 2003–2006 United States National Health and Nutrition Examination Survey. BMI z scores (zBMI) (n  = 3,161) and MetS (n  = 1,379) were calculated using age‐ and sex‐specific criteria for adolescents. TV viewing (h/day) was measured via a self‐reported questionnaire, and dietary intake was assessed using two 24‐h recalls. Using the MacKinnon method, a series of mediation analyses were conducted examining five dietary mediators (total energy intake, fruit and vegetable intake, discretionary snacks, sugar‐sweetened beverages and diet quality) of the relationships between TV viewing and zBMI and MetS. Results Small positive relationships were observed between TV viewing and zBMI (β = 0.99, p  < 0.001) and TV viewing and MetS (OR = 1.18, p  = 0.046). No dietary element appeared to mediate the relationship between TV viewing and zBMI. However, sugar‐sweetened beverage consumption and fruit and vegetable intake partially mediated the relationship between TV viewing and MetS, explaining 8.7% and 4.1% of the relationship, respectively. Conclusions These findings highlight the complexity of the relationships between TV viewing, dietary intake and cardiometabolic health outcomes, and that TV viewing should remain a target for interventions

Empirical ways to identify novel Bedaquiline resistance mutations in AtpE.

Clinical resistance against Bedaquiline, the first new anti-tuberculosis compound with a novel mechanism of action in over 40 years, has already been detected in Mycobacterium tuberculosis. As a new drug, however, there is currently insufficient clinical data to facilitate reliable and timely identification of genomic determinants of resistance. Here we investigate the structural basis for M. tuberculosis associated bedaquiline resistance in the drug target, AtpE. Together with the 9 previously identified resistance-associated variants in AtpE, 54 non-resistance-associated mutations were identified through comparisons of bedaquiline susceptibility across 23 different mycobacterial species. Computational analysis of the structural and functional consequences of these variants revealed that resistance associated variants were mainly localized at the drug binding site, disrupting key interactions with bedaquiline leading to reduced binding affinity. This was used to train a supervised predictive algorithm, which accurately identified likely resistance mutations (93.3% accuracy). Application of this model to circulating variants present in the Asia-Pacific region suggests that current circulating variants are likely to be susceptible to bedaquiline. We have made this model freely available through a user-friendly web interface called SUSPECT-BDQ, StrUctural Susceptibility PrEdiCTion for bedaquiline (http://biosig.unimelb.edu.au/suspect_bdq/). This tool could be useful for the rapid characterization of novel clinical variants, to help guide the effective use of bedaquiline, and to minimize the spread of clinical resistance.M.K was funded by the Melbourne Research Scholarship. D.B.A was funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (MR/M026302/1), the Jack Brockhoff Foundation (JBF 4186, 2016), and a C. J. Martin Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1072476). The Vietnam genomic dataset was funded by a NHMRC Australia grant (APP1056689) to SJD and KEH. Supported in part by the Victorian Government's OIS Program

Engineering enzymes with non-canonical active site functionality

The combination of computational enzyme design and laboratory evolution provides an attractive platform for the creation of protein catalysts with new function. To date, designed mechanisms have relied upon Nature’s alphabet of 20 genetically encoded amino acids, which greatly restricts the range of functionality which can be installed into enzyme active sites. Here, we have exploited engineered components of the cellular translation machinery to create a protein catalyst which operates via a non-canonical catalytic nucleophile. We have subsequently shown that powerful laboratory evolution protocols can be readily adapted to allow optimization of enzymes containing non-canonical active site functionality. Crystal structures obtained along the evolutionary trajectory highlight the origins of improved activity. Thus our approach merges beneficial features of organo- and biocatalysis, by combining the intrinsic reactivities and greater versatility of small molecule catalysts with the rate enhancements, reaction selectivities and evolvability of proteins. Please click Additional Files below to see the full abstract

Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population

<p>Abstract</p> <p>Background</p> <p>In Vietnam the blackwater fever syndrome (BWF) has been associated with malaria infection, quinine ingestion and G6PD deficiency. The G6PD variants within the Vietnamese Kinh contributing to the disease risk in this population, and more generally to haemoglobinuria, are currently unknown.</p> <p>Method</p> <p>Eighty-two haemoglobinuria patients and 524 healthy controls were screened for G6PD deficiency using either the methylene blue reduction test, the G-6-PDH kit or the micro-methaemoglobin reduction test. The G6PD gene variants were screened using SSCP combined with DNA sequencing in 82 patients with haemoglobinuria, and in 59 healthy controls found to be G6PD deficient.</p> <p>Results</p> <p>This study confirmed that G6PD deficiency is strongly associated with haemoglobinuria (OR = 15, 95% CI [7.7 to 28.9], P < 0.0001). Six <it>G6PD </it>variants were identified in the Vietnamese population, of which two are novel (Vietnam1 [Glu³Lys] and Vietnam2 [Phe⁶⁶Cys]). G6PD Viangchan [Val²⁹¹Met], common throughout south-east Asia, accounted for 77% of the variants detected and was significantly associated with haemoglobinuria within G6PD-deficient ethnic Kinh Vietnamese (OR = 5.8 95% CI [114-55.4], P = 0.022).</p> <p>Conclusion</p> <p>The primary frequency of several <it>G6PD </it>mutations, including novel mutations, in the Vietnamese Kinh population are reported and the contribution of <it>G6PD </it>mutations to the development of haemoglobinuria are investigated.</p