Mobility gradients yield rubbery surfaces on top of polymer glasses.

Many emerging materials, such as ultrastable glasses1,2 of interest for phone displays and OLED television screens, owe their properties to a gradient of enhanced mobility at the surface of glass-forming liquids. The discovery of this surface mobility enhancement3-5 has reshaped our understanding of the behaviour of glass formers and of how to fashion them into improved materials. In polymeric glasses, these interfacial modifications are complicated by the existence of a second length scale-the size of the polymer chain-as well as the length scale of the interfacial mobility gradient6-9. Here we present simulations, theory and time-resolved surface nano-creep experiments to reveal that this two-scale nature of glassy polymer surfaces drives the emergence of a transient rubbery, entangled-like surface behaviour even in polymers comprised of short, subentangled chains. We find that this effect emerges from superposed gradients in segmental dynamics and chain conformational statistics. The lifetime of this rubbery behaviour, which will have broad implications in constraining surface relaxations central to applications including tribology, adhesion, and surface healing of polymeric glasses, extends as the material is cooled. The surface layers suffer a general breakdown in time-temperature superposition (TTS), a fundamental tenet of polymer physics and rheology. This finding may require a reevaluation of strategies for the prediction of long-time properties in polymeric glasses with high interfacial areas. We expect that this interfacial transient elastomer effect and TTS breakdown should normally occur in macromolecular systems ranging from nanocomposites to thin films, where interfaces dominate material properties5,10.

Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy.

BACKGROUND: Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS: We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS: A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, -0.04 kg; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS: Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.).

Call to action for a life course approach.

Gestational diabetes remains the most common medical disorder in pregnancy, with short-term and long-term consequences for mothers and offspring. New insights into pathophysiology and management suggest that the current gestational diabetes treatment approach should expand from a focus on late gestational diabetes to a personalised, integrated life course approach from preconception to postpartum and beyond. Early pregnancy lifestyle intervention could prevent late gestational diabetes. Early gestational diabetes diagnosis and treatment has been shown to be beneficial, especially when identified before 14 weeks of gestation. Early gestational diabetes screening now requires strategies for integration into routine antenatal care, alongside efforts to reduce variation in gestational diabetes care, across settings that differ between, and within, countries. Following gestational diabetes, an oral glucose tolerance test should be performed 6-12 weeks postpartum to assess the glycaemic state. Subsequent regular screening for both dysglycaemia and cardiometabolic disease is recommended, which can be incorporated alongside other family health activities. Diabetes prevention programmes for women with previous gestational diabetes might be enhanced using shared decision making and precision medicine. At all stages in this life course approach, across both high-resource and low-resource settings, a more systematic process for identifying and overcoming barriers to preventative care and treatment is needed to reduce the current global burden of gestational diabetes.

Pathophysiology from preconception, during pregnancy, and beyond.

Gestational diabetes is the most common medical complication in pregnancy. Historically, gestational diabetes was considered a pregnancy complication involving treatment of rising glycaemia late in the second trimester. However, recent evidence challenges this view. Pre-pregnancy and pregnancy-specific factors influence gestational glycaemia, with open questions regarding roles of non-glycaemic factors in the aetiology and consequences of gestational diabetes. Varying patterns of insulin secretion and resistance in early and late pregnancy underlie a heterogeneity of gestational diabetes in the timing and pathophysiological subtypes with clinical implications: early gestational diabetes and insulin resistant gestational diabetes subtypes are associated with a higher risk of pregnancy complications. Metabolic perturbations of early gestational diabetes can affect early placental development, affecting maternal metabolism and fetal development. Fetal hyperinsulinaemia can affect the development of multiple fetal tissues, with short-term and long-term consequences. Pregnancy complications are prevented by managing glycaemia in early and late pregnancy in some, but not all women with gestational diabetes. A better understanding of the pathophysiology and heterogeneity of gestational diabetes will help to develop novel management approaches with focus on improved prevention of maternal and offspring short-term and long-term complications, from pre-conception, throughout pregnancy, and beyond.

Epidemiology and management of gestational diabetes.

Gestational diabetes is defined as hyperglycaemia first detected during pregnancy at glucose concentrations that are less than those of overt diabetes. Around 14% of pregnancies globally are affected by gestational diabetes; its prevalence varies with differences in risk factors and approaches to screening and diagnosis; and it is increasing in parallel with obesity and type 2 diabetes. Gestational diabetes direct costs are US$1·6 billion in the USA alone, largely due to complications including hypertensive disorders, preterm delivery, and neonatal metabolic and respiratory consequences. Between 30% and 70% of gestational diabetes is diagnosed in early pregnancy (ie, early gestational diabetes defined by hyperglycaemia before 20 weeks of gestation). Early gestational diabetes is associated with worse pregnancy outcomes compared with women diagnosed with late gestational diabetes (hyperglycaemia from 24 weeks to 28 weeks of gestation). Randomised controlled trials show benefits of treating gestational diabetes from 24 weeks to 28 weeks of gestation. The WHO 2013 recommendations for diagnosing gestational diabetes (one-step 75 gm 2-h oral glucose tolerance test at 24-28 weeks of gestation) are largely based on the Hyperglycemia and Adverse Pregnancy Outcomes Study, which confirmed the linear association between pregnancy complications and late-pregnancy maternal glycaemia: a phenomenon that has now also been shown in early pregnancy. Recently, the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) trial showed benefit in diagnosis and treatment of early gestational diabetes for women with risk factors. Given the diabesity epidemic, evidence for gestational diabetes heterogeneity by timing and subtype, and advances in technology, a life course precision medicine approach is urgently needed, using evidence-based prevention, diagnostic, and treatment strategies.

Author Correction: The mid-developmental transition and the evolution of animal body plans.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Phagocytosis of aggrecan-positive perineuronal nets surrounding motor neurons by reactive microglia expressing MMP-9 in TDP-43Q331K ALS model mice.

Perineuronal nets (PNNs) are extracellular matrix structures that surround excitable neurons and their proximal dendrites. PNNs play an important role in neuroprotection against oxidative stress. Oxidative stress within motor neurons can act as a trigger for neuronal death, and this has been implicated in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We therefore characterised PNNs around alpha motor neurons and the possible contributing cellular factors in the mutant TDP-43Q331K transgenic mouse, a slow onset ALS mouse model. PNNs around alpha motor neurons showed significant loss at mid-stage disease in TDP-43Q331K mice compared to wild type strain control mice. PNN loss coincided with an increased expression of matrix metallopeptidase-9 (MMP-9), an endopeptidase known to cleave PNNs, within the ventral horn. During mid-stage disease, increased numbers of microglia and astrocytes expressing MMP-9 were present in the ventral horn of TDP-43Q331K mice. In addition, TDP-43Q331K mice showed increased levels of aggrecan, a PNN component, in the ventral horn by microglia and astrocytes during this period. Elevated aggrecan levels within glia were accompanied by an increase in fractalkine expression, a chemotaxic protein responsible for the recruitment of microglia, in alpha motor neurons of onset and mid-stage TDP-43Q331K mice. Following PNN loss, alpha motor neurons in mid-stage TDP-43Q331K mice showed increased 3-nitrotyrosine expression, an indicator of protein oxidation. Together, our observations along with previous PNN research provide suggests a possible model whereby microglia and astrocytes expressing MMP-9 degrade PNNs surrounding alpha motor neurons in the TDP-43Q331K mouse. This loss of nets may expose alpha-motor neurons to oxidative damage leading to degeneration of the alpha motor neurons in the TDP-43Q331K ALS mouse model.

Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: A stepped wedge cluster randomised trial.

BACKGROUND: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. METHODS AND FINDINGS: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. CONCLUSIONS: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term. TRIAL REGISTRATION: The trial is registered with ISRCTN (41918550).

Perineuronal nets are phagocytosed by MMP-9 expressing microglia and astrocytes in the SOD1G93A ALS mouse model.

AIMS: Perineuronal nets (PNNs) are an extracellular matrix structure that encases excitable neurons. PNNs play a role in neuroprotection against oxidative stress. Oxidative stress within motor neurons can trigger neuronal death, which has been implicated in amyotrophic lateral sclerosis (ALS). We investigated the spatio-temporal timeline of PNN breakdown and the contributing cellular factors in the SOD1G93A strain, a fast-onset ALS mouse model. METHODS: This was conducted at the presymptomatic (P30), onset (P70), mid-stage (P130), and end-stage disease (P150) using immunofluorescent microscopy, as this characterisation has not been conducted in the SOD1G93A strain. RESULTS: We observed a significant breakdown of PNNs around α-motor neurons in the ventral horn of onset and mid-stage disease SOD1G93A mice compared with wild-type controls. This was observed with increased numbers of microglia expressing matrix metallopeptidase-9 (MMP-9), an endopeptidase that degrades PNNs. Microglia also engulfed PNN components in the SOD1G93A mouse. Further increases in microglia and astrocyte number, MMP-9 expression, and engulfment of PNN components by glia were observed in mid-stage SOD1G93A mice. This was observed with increased expression of fractalkine, a signal for microglia engulfment, within α-motor neurons of SOD1G93A mice. Following PNN breakdown, α-motor neurons of onset and mid-stage SOD1G93A mice showed increased expression of 3-nitrotyrosine, a marker for protein oxidation, which could render them vulnerable to death. CONCLUSIONS: Our observations suggest that increased numbers of MMP-9 expressing glia and their subsequent engulfment of PNNs around α-motor neurons render these neurons sensitive to oxidative damage and eventual death in the SOD1G93A ALS model mouse.

Cancer risk following onset of type 2 diabetes in New Zealanders with impaired glucose tolerance over 25 years: a matched prospective cohort study.

BACKGROUND: In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994-2019, assessing 5- and 10-year cancer risks. METHODS: Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1-5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks. RESULTS: The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09-1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk. CONCLUSIONS: T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential.

A qualitative study of the perceptions and experiences of participants and healthcare professionals in the DiRECT-Australia type 2 diabetes remission service.

BACKGROUND: The UK Diabetes Remission Clinical Trial (DiRECT) study was replicated in an Australian primary care setting. This qualitative study aimed to explore and understand the perceptions and experiences of both participants and healthcare professionals (HCPs) involved in the DiRECT-Australia Type 2 Diabetes Remission Service. METHODS: All participants and HCPs delivering the service were invited to participate in semi-structured interviews via online videoconferencing. The interview guides explored perceptions and experiences in DiRECT-Australia, covering aspects such as barriers and facilitators to recruitment and participation, motivations and challenges across service phases, adequacy of support provided and the overall acceptability of the service. All interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Eight DiRECT-Australia participants and six HCPs (three general practitioners, two practice nurses and one dietitian) participated. Four overarching themes were identified: (1) Enablers and barriers to recruitment and continuous participation in DiRECT-Australia; (2) Motivators and overcoming barriers across the total diet replacement, food reintroduction and weight maintenance phases; (3) Importance of participant-HCP interactions and continuous support; (4) Acceptance and long-term need for DiRECT-Australia. Adherence to total diet replacement was less challenging than anticipated by participants. Transitioning to the food reintroduction phase was difficult but overcome through HCP support. DiRECT-Australia was well accepted by both participants and HCPs, and participants expressed willingness to continue with the service, if provided on a long-term basis. CONCLUSIONS: Both participants and HCPs were highly interested in the new diabetes remission service set up in an Australian primary care setting. The acceptability of DiRECT-Australia was underscored by participants emphasising the effectiveness of the service in achieving significant weight loss and diabetes remission. There is a need for long-term and wider implementation of the service to ensure that anyone with recent onset type 2 diabetes is offered the best possible chance to achieve remission.

All-cause, premature, and cardiovascular death attributable to socioeconomic and ethnic disparities among New Zealanders with type 1 diabetes 1994-2019: a multi-linked population-based cohort study.

BACKGROUND: New Zealand (NZ) research into type 1 diabetes mellitus (T1DM) mortality can inform policy and future research. In this study we aimed to quantify the magnitude to which ethnicity and socioeconomic disparities influenced mortality at the population level among people with Type 1 diabetes (T1DM) in Auckland, New Zealand (NZ). METHODS: The cohort data were derived from the primary care diabetes audit program the Diabetes Care Support Service (DCSS), and linked with national primary care, pharmaceutical claims, hospitalisation, and death registration databases. People with T1DM enrolled in DCSS between 1994-2018 were included. All-cause, premature, and cardiovascular mortalities were estimated by Poisson regression models with adjustment for population-level confounders. The mortality rates ratio (MRR) was standardized against the DCSS type 2 diabetes population. Mortality rates were compared by ethnic group (NZ European (NZE) and non-NZE) and socioeconomic deprivation quintile. The population attributable fraction (PAF) was estimated for ethnic and socioeconomic disparities by Cox regression adjusting for demographic, lifestyle, and clinical covariates. The adjusted slope index inequality (SII) and relative index of inequality (RII) were used to measure the socioeconomic disparity in mortalities. RESULTS: Overall, 2395 people with T1DM (median age 34.6 years; 45% female; 69% NZE) were enrolled, among whom the all-cause, premature and CVD mortalities were 6.69 (95% confidence interval: 5.93-7.53), 3.30 (2.77-3.90) and 1.77 (1.39-2.23) per 1,000 person-years over 25 years. The overall MRR was 0.39 (0.34-0.45), 0.65 (0.52-0.80), and 0.31 (0.24-0.41) for all-cause, premature and CVD mortality, respectively. PAF attributable to ethnicity disparity was not significantly different for mortality. The adjusted PAF indicated that 25.74 (0.84-44.39)% of all-cause mortality, 25.88 (0.69-44.69)% of premature mortality, 55.89 (1.20-80.31)% of CVD mortality could be attributed to socioeconomic inequality. The SII was 8.04 (6.30-9.78), 4.81 (3.60-6.02), 2.70 (1.82-3.59) per 1,000 person-years and RII was 2.20 (1.94-2.46), 2.46 (2.09-2.82), and 2.53 (2.03-3.03) for all-cause, premature and CVD mortality, respectively. CONCLUSIONS: Our results suggest that socioeconomic disparities were responsible for a substantial proportion of all-cause, premature and CVD mortality in people with T1DM in Auckland, NZ. Reducing socioeconomic barriers to management and self-management would likely improve clinical outcomes.

Nature of dynamic gradients, glass formation, and collective effects in ultrathin freestanding films.

Molecular, polymeric, colloidal, and other classes of liquids can exhibit very large, spatially heterogeneous alterations of their dynamics and glass transition temperature when confined to nanoscale domains. Considerable progress has been made in understanding the related problem of near-interface relaxation and diffusion in thick films. However, the origin of "nanoconfinement effects" on the glassy dynamics of thin films, where gradients from different interfaces interact and genuine collective finite size effects may emerge, remains a longstanding open question. Here, we combine molecular dynamics simulations, probing 5 decades of relaxation, and the Elastically Cooperative Nonlinear Langevin Equation (ECNLE) theory, addressing 14 decades in timescale, to establish a microscopic and mechanistic understanding of the key features of altered dynamics in freestanding films spanning the full range from ultrathin to thick films. Simulations and theory are in qualitative and near-quantitative agreement without use of any adjustable parameters. For films of intermediate thickness, the dynamical behavior is well predicted to leading order using a simple linear superposition of thick-film exponential barrier gradients, including a remarkable suppression and flattening of various dynamical gradients in thin films. However, in sufficiently thin films the superposition approximation breaks down due to the emergence of genuine finite size confinement effects. ECNLE theory extended to treat thin films captures the phenomenology found in simulation, without invocation of any critical-like phenomena, on the basis of interface-nucleated gradients of local caging constraints, combined with interfacial and finite size-induced alterations of the collective elastic component of the structural relaxation process.

Adequacy of health message tailoring for ethnic minorities: Pasifika communities in Sydney, Australia, during COVID-19.

Ethnic minorities, such as Pasifika, residing in high-income countries were at higher risk of COVID-19 infection during the pandemic. To understand the experiences of Pasifika, including message dissemination and barriers to tailored public health messaging during the pandemic, a qualitative study was undertaken, underpinned by Laswell's Model of Communication and Bandura's social cognitive theory with data collected using Pasifika methods. Pasifika adults (n = 65) were recruited across Sydney from July 2020 to March 2022. Health care professionals (HCP) (n = 17) employed by four local health districts (LHDs) and Pasifika community-based organizations delivering multicultural COVID-19-related work within the study catchment, were also recruited. Five themes were constructed from the data of: (i) prevailing fear and uncertainty over COVID-19 infection and losing employment; (ii) limited knowledge of government perpetuating distrust in Government as a benevolent source of information; (iii) faith and trust as priorities for health decision-making; (iv) 'Coconut wireless'-the role of family, friends and community in disseminating public health messages through word of mouth; and (v) limited health literacy affecting compliance with public health orders. Community members identified important messages and resources had not been sufficiently distributed. Most HCPs understood the necessity of grassroots-level engagement but reported existing approaches were inadequate to navigate challenges. These findings highlight the need for public health promotion and communication strategies that consider both the social and cultural determinants of health. We propose a 7-point checklist as a cultural appropriateness lens to assist the development and rating of existing or new health promotion messaging and resources.

The first International Association of Diabetes and Pregnancy Study Groups summit on the diagnosis of gestational diabetes in early pregnancy: TOBOGM Summit Report.

The first International Association of Diabetes and Pregnancy Study Groups Summit on the diagnosis of gestational diabetes in early pregnancy (Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) Summit) was held on the 17 November 2022 in Sydney, Australia. It sought to use the TOBOGM trial findings to scope the issues involved with early screening, to inform future discussions over possible approaches for diagnosing gestational diabetes mellitus (GDM) in early pregnancy. Most delegates supported testing for early GDM using a one-step 75 g oral glucose tolerance test approach with Canadian Diabetes Association criteria preferred, but highlighted the importance of considering resources, cost, consumer perspectives and equity in translating TOBOGM results into a clinical approach to screening for, and diagnosing, early GDM.

Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years.

INTRODUCTION: We aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years. METHODS: Tapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models. RESULTS: The onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures. DISCUSSION: Our findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds. HIGHLIGHTS: Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

Chronic pain and the use of complementary and alternative medicine in rural Victoria, Australia.

OBJECTIVE: The relationship between chronic pain and complementary and alternative medicine (CAM) use is poorly understood, and the situation in rural Australia is particularly unclear. The objective here was to determine the socio-demographic factors associated with the use of CAM for the treatment of chronic pain in a region of rural Australia. METHODS: This secondary analysis used data from a population health survey, Crossroads-II, to assess the relationships of various socio-demographic factors with the use of CAM by those suffering from chronic pain. DESIGN: Face-to-face surveys at households randomly selected from residential address lists. SETTING: A large regional centre and three nearby rural towns in northern Victoria, Australia. PARTICIPANTS: Sixteen years of age and older. MAIN OUTCOME MEASURES: Use of a CAM service to treat chronic pain. RESULTS: Being female (2.40 [1.47, 3.93], p < 0.001) and having a bachelor's degree (OR 2.24 [1.20, 4.20], p < 0.001) had a significant positive relationship with the use of CAM overall to redress chronic pain and those 50 years and older had greater odds of using manipulation therapies relative to those below 50 years (50-64: OR 0.52 [0.32, 0.86], p = 0.010; 65+: 0.37 [0.18, 0.75], p = 0.005). CONCLUSION: In the studied region, females and those with university education have the greatest odds of using CAM to treat chronic pain. This study needs to be complemented with more mechanistic investigations into the reasons people make the decisions they make about using CAM for the management of chronic pain.

Effect of onset of type 2 diabetes on risks of cardiovascular disease and heart failure among new Zealanders with impaired glucose tolerance over 25 years: tapered-matched landmark analysis.

BACKGROUND: This study aimed to examine the association between the incident onset of T2DM and 5- and 10-year risks of CVD and HF in people with IGT identified in primary care in South and West Auckland, New Zealand (NZ) between 1994 and 2019. METHODS: We compared CVD and HF risks in patients with IGT and with/without T2D newly diagnosed within the exposure window (1-5 years). Tapered matching and landmark analysis (to account for immortal bias) were used to control for potential effects of known confounders. RESULTS: Among 26,794 patients enrolled with IGT, 845 had T2D newly diagnosed within 5 years from enrolment (landmark date) and 15,452 did not have T2D diagnosed. Patients progressing to T2D (vs. those not progressing) had a similar 5-year risk for CVD (hazard ratio 1.19; 95% CI 0.61-2.32) but significantly higher 10-year risk of CVD (2.45(1.40-4.29)), 5-year risk of HF (1.94(1.20-3.12)) and 10-year risk of HF (2.84(1.83-4.39). The association between the onset of T2D and risk of 10-year risk of CVD, 5-year and 10-year risk of HF was more likely among men, the socioeconomically deprived, those currently smoking, patients with higher metabolic measures and/or those with lower renal function. Patients of NZ European ethnicity had a lower 10-year risk of CVD. CONCLUSIONS: The study suggests that the diagnosis of T2D mediates the risk of CVD and HF in people with IGT. The development of risk scores to identify and better manage individuals with IGT at high risk of T2D is warranted.

Glass formation and dynamics of model polymer films with one versus two active interfaces.

Polymers and other glass-forming liquids can exhibit profound alterations in dynamics in the nanoscale vicinity of interfaces, over a range appreciably exceeding that of typical interfacial thermodynamic gradients. The understanding of these dynamical gradients is particularly complicated in systems with internal or external nanoscale dimensions, where a gradient nucleated at one interface can impinge on a second, potentially distinct, interface. To better understand the interactions that govern system dynamics and glass formation in these cases, here we simulate the baseline case of a glass-forming polymer film, over a wide range of thickness, supported on a dynamically neutral substrate that has little effect on nearby dynamics. We compare these results to our prior simulations of freestanding films. Results indicate that dynamical gradients in our simulated systems, as measured based upon translational relaxation, are simply truncated when they impinge on a secondary surface that is locally dynamically neutral. Altered film behavior can be described almost entirely by gradient effects down to the thinnest films probed, with no evidence for finite-size effects sometimes posited to play a role in these systems. Finally, our simulations predict that linear gradient overlap effects in the presence of symmetric dynamically active interfaces yield a non-monotonic variation of the whole free standing film stretching exponent (relaxation time distribution breadth). The maximum relaxation time distribution breadth in simulation is found at a film thickness of 4-5 times the interfacial gradient range. Observation of this maximum in experiment would provide an important validation that the gradient behavior observed in simulation persists to experimental timescales. If validated, observation of this maximum would potentially also enable determination of the dynamic gradient range from experimental mean-film measurements of film dynamics.

Previous pre-eclampsia, gestational diabetes mellitus and the risk of cardiovascular disease: A nested case-control study in Sweden.

OBJECTIVE: Pre-eclampsia and gestational diabetes mellitus (GDM) are two common pregnancy complications that affect birth outcomes and are associated with a long-term risk of cardiovascular disease (CVD). The aims of this study were to investigate if the pre-eclampsia association with CVD is independent of GDM and modified by body mass index (BMI) or GDM. DESIGN: Case-control study. SETTING: Sweden. POPULATION: Cases were women with a first CVD event between 1991 and 2008 and a previous pregnancy who were matched with controls without CVD (1:5) by year of birth, age and region of birth. METHODS: Conditional logistic regression was used to evaluate the associations of GDM, pre-eclampsia and maternal BMI with CVD adjusted for potential confounders and effect modifications with interaction tests. MAIN OUTCOME MEASURES: CVD. RESULTS: There were 2639 cases and 13 310 controls with complete data. Pre-eclampsia and GDM were independent risk factors for CVD (adjusted odds ratio [aOR] 2.59, 95% CI 2.12-3.17 and aOR 1.47, 95% CI 1.04-2.09, respectively). After stratifying by maternal BMI, the adjusted association of pre-eclampsia with CVD did not differ notably between BMI groups: normal weight (aOR 2.65, 95% CI 1.90-3.69), overweight (aOR 2.67, 95% CI 1.52-4.68) and obesity (aOR 3.03, 95% CI 0.74-12.4). Similar findings were seen when stratifying on GDM/non-GDM. CONCLUSIONS: Pre-eclampsia and GDM are independent risk factors for later CVD and having both during pregnancy is a major risk factor for later CVD. The association between pre-eclampsia and CVD is not modified by BMI. Effective CVD preventive programs for high-risk women are urgently needed in order to improve women's long-term health.