Measurement error in a multi-level analysis of air pollution and health: a simulation study.

BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models

Hospitalization for heart disease, stroke, and diabetes mellitus among Indian-born persons: a small area analysis

BACKGROUND: We set out to describe the risk of hospitalization from heart disease, stroke, and diabetes among persons born in India, all foreign-born persons, and U.S.-born persons residing in New York City. METHODS: We examined billing records of 1,083,817 persons hospitalized in New York City during the year 2000. The zip code of each patient's residence was linked to corresponding data from the 2000 U.S. Census to obtain covariates not present in the billing records. Using logistic models, we evaluated the risk of hospitalization for heart disease, stroke and diabetes by country of origin. RESULTS: After controlling for covariates, Indian-born persons are at similar risk of hospitalization for heart disease (RR = 1.02, 95% confidence interval 1.02, 1.03), stroke (RR = 1.00, 95% confidence interval, 0.99, 1.01), and diabetes mellitus (RR = 0.96 95% confidence interval 0.94, 0.97) as native-born persons. However, Indian-born persons are more likely to be hospitalized for these diseases than other foreign-born persons. For instance, the risk of hospitalization for heart disease among foreign-born persons is 0.70 (95% confidence interval 0.67, 0.72) and the risk of hospitalization for diabetes is 0.39 (95% confidence interval 0.37, 0.42) relative to native-born persons. CONCLUSIONS: South Asians have considerably lower rates of hospitalization in New York than reported in countries with national health systems. Access may play a role. Clinicians working in immigrant settings should nonetheless maintain a higher vigilance for these conditions among Indian-born persons than among other foreign-born populations

Electrically-driven phase transition in magnetite nanostructures

Magnetite (Fe$_{3}$O$_{4}$), an archetypal transition metal oxide, has been used for thousands of years, from lodestones in primitive compasses[1] to a candidate material for magnetoelectronic devices.[2] In 1939 Verwey[3] found that bulk magnetite undergoes a transition at T$_{V}$ $\approx$ 120 K from a high temperature "bad metal" conducting phase to a low-temperature insulating phase. He suggested[4] that high temperature conduction is via the fluctuating and correlated valences of the octahedral iron atoms, and that the transition is the onset of charge ordering upon cooling. The Verwey transition mechanism and the question of charge ordering remain highly controversial.[5-11] Here we show that magnetite nanocrystals and single-crystal thin films exhibit an electrically driven phase transition below the Verwey temperature. The signature of this transition is the onset of sharp conductance switching in high electric fields, hysteretic in voltage. We demonstrate that this transition is not due to local heating, but instead is due to the breakdown of the correlated insulating state when driven out of equilibrium by electrical bias. We anticipate that further studies of this newly observed transition and its low-temperature conducting phase will shed light on how charge ordering and vibrational degrees of freedom determine the ground state of this important compound.Comment: 17 pages, 4 figure

Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair

Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of PDHA1 (NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency

Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.

Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of PDHA1 (NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency

Acquiring a pet dog significantly reduces stress of primary carers for children with autism spectrum disorder: a prospective case control study

This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3–10 weeks after acquisition) and follow-up (25–40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD

The use of complementary and alternative medicines among patients with locally advanced breast cancer – a descriptive study

BACKGROUND: Complementary and alternative medicine (CAM) use is common among cancer patients. This paper reviews the use of CAM in a series of patients with locally advanced breast cancer (LABC). METHODS: Women with LABC attending a specialist clinic at a single Canadian cancer centre were identified and approached. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer and of dying of breast cancer. Responses were scored and compared between CAM users and non-users. RESULTS: Thirty-six patients were approached, 32 completed the questionnaire (response rate 89%). Forty-seven percent of LABC patients were identified as CAM users. CAM users were more likely to be younger, married, in a higher socioeconomic class and of Asian ethnicity than non-users. CAM users were likely to use multiple modalities simultaneously (median 4) with vitamins being the most popular (60%). Motivation for CAM therapy was described as, "assisting their body to heal" (75%), to 'boost the immune system' (56%) and to "give a feeling of control with respect to their treatment" (56%). CAM therapy was used concurrently with conventional treatment in 88% of cases, however, 12% of patients felt that CAM could replace their conventional therapy. Psychological evaluation suggests CAM users perceived their risk of dying of breast cancer was similar to that of the non-Cam group (33% vs. 35%), however the CAM group had less severe anxiety and depression. CONCLUSION: The motivation, objectives and benefits of CAM therapy in a selected population of women with LABC are similar to those reported for women diagnosed with early stage breast cancer. CAM users display less anxiety and depression and are less likely to believe they will die of their breast cancer. However the actual benefit to overall and disease free survival has yet to be demonstrated, as well as the possible interactions with conventional therapy. Consequently more research is needed in this ever-growing field

Nepal's War on Human Rights: A summit higher than Everest

Nepal has witnessed serious human rights violations including arbitrary arrests, detentions, "disappearances", extra judicial executions, abductions and torture carried out by both the Royal Nepalese Army and the Maoist rebels in the 10 years of the "peoples war". Women and children have borne the brunt of the conflict. Massive displacement has led to adverse social and psychological consequences. While the reasons for the conflict are mainly indigenous and rooted in the social and economic in-equities, remedies for health inequities must come not only from the health sector but also from broad social policies and adopting a participatory and conflict-sensitive approach to development. Meanwhile the international community needs to use its leverage to urge both sides to accept a human rights accord and honor international human rights and humanitarian laws, while investigating allegations of abuse and prosecute those responsible

Lifestyle factors and primary glioma and meningioma tumours in the Million Women Study cohort

Previous studies have reported inconsistent results on the effect of anthropometric and lifestyle factors on the risk of developing glioma or meningioma tumours. A prospective cohort of 1.3 million middle-aged women was used to examine these relationships. During 7.7 million women-years of follow-up, a total of 1563 women were diagnosed with a primary incident central nervous system tumour: 646 tumours were classified as glioma and 390 as meningioma. Our results show that height is related to the incidence of all central nervous system tumours with a risk of about 20% per 10 cm increase in height (relative risk=1.19, 95% CI=1.10–1.30 per 10 cm increase in height, P<0.001): the risks did not differ significantly between specified glioma and meningioma. Body mass index (BMI) was also related to central nervous system tumour incidence, with a risk of about 20% per 10 kg m−2 increase in BMI (relative risk=1.17, 95% CI=1.03–1.34 per 10 kg m−2 increase in BMI, P=0.02). Smoking status, alcohol intake, socioeconomic level, parity, age at first birth, and oral contraceptive use were not associated with the risk of glioma or meningioma tumours. In conclusion, for women in the United Kingdom, the incidence of glioma or meningioma tumours increases with increasing height and increasing BMI