Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies

Aims/hypothesis The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible.

Methods A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.

Results In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors’ adjustments for potential confounding made a substantial difference to the pooled ORs.

Conclusions/interpretation This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.

Does childhood bullying lead to the development of psychotic symptoms? A meta-analysis and review of prospective studies

Purpose: Researchers have demonstrated associations between trauma and psychosis. Childhood trauma, in particular, appears to be an important determinant. Recently, bullying has become considered a traumatic experience in its own right. This review aims to analyse research with prospective designs, which will enable conclusions about whether or not bullying causes psychosis.

Methods: A systematic review of the literature was carried out independently by two reviewers. Eligibility and quality assessment criteria were applied. A meta-analysis and narrative synthesis were then completed.

Results: Ten studies met inclusion criteria. Four used data from the same large database, and were combined as one. The majority provided confirmation that bullying appears to cause later development of psychosis. A meta-analysis yielded an unadjusted odds ratio (OR) of 2.148 [95% confidence interval (CI) 1.140–4.044].

Conclusions: The studies reviewed here suggest that bullying does predict the later development of psychotic symptoms. What is lacking from the literature is adequate investigation into other potential mediating factors. The current review highlights the significant role of bullying within this complex interaction. Potential mediating variables are explored, including a dose–response effect for the severity and frequency of victimization. Suggestions for targeting intervention are also suggested alongside clinical implications and recommendations for future research.

The effectiveness of disaster risk communication: a systematic review of intervention studies

INTRODUCTION: A disaster is a serious disruption to the functioning of a community that exceeds its capacity to cope within its own resources. Risk communication in disasters aims to prevent and mitigate harm from disasters, prepare the population before a disaster, disseminate information during disasters and aid subsequent recovery. The aim of this systematic review is to identify, appraise and synthesise the findings of studies of the effects of risk communication interventions during four stages of the disaster cycle.

METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PsycInfo, Sociological Abstracts, Web of Science and grey literature sources for randomised trials, cluster randomised trials, controlled and uncontrolled before and after studies, interrupted time series studies and qualitative studies of any method of disaster risk communication to at-risk populations. Outcome criteria were disaster-related knowledge and behaviour, and health outcomes.

RESULTS: Searches yielded 5,224 unique articles, of which 100 were judged to be potentially relevant. Twenty-five studies met the inclusion criteria, and two additional studies were identified from other searching. The studies evaluated interventions in all four stages of the disaster cycle, included a variety of man-made, natural and infectious disease disasters, and were conducted in many disparate settings. Only one randomised trial and one cluster randomised trial were identified, with less robust designs used in the other studies. Several studies reported improvements in disaster-related knowledge and behaviour.

DISCUSSION: We identified and appraised intervention studies of disaster risk communication and present an overview of the contemporary literature. Most studies used non-randomised designs that make interpretation challenging. We do not make specific recommendations for practice but highlight the need for high-quality randomised trials and appropriately-analysed cluster randomised trials in the field of disaster risk communication where these can be conducted within an appropriate research ethics framework.

Aflatoxin Exposure and Associated Human Health Effects, a Review of Epidemiological Studies

flatoxins are fungal toxins that possess acute life threatening toxicity, carcinogenic properties and other potential chronic adverse effects. Dietary exposure to aflatoxins is considered a major public health concern, especially for subsistence farming communities in sub-Saharan Africa and South Asia, where dietary staple food crops such as groundnuts and maize are often highly contaminated with aflatoxin due to hot and humid climates and poor storage, together with low awareness of risk and lack of enforcement of regulatory limits. Biomarkers have been developed and applied in many epidemiological studies assessing aflatoxin exposure and the associated health effects in these high-risk population groups. This review discusses the recent epidemiological evidence for aflatoxin exposure, co-exposure with other mycotoxins and associated health effects in order to provide evidence on risk assessment, and highlight areas where further research is necessary. Aflatoxin exposure can occur at any stage of life and is a major risk factor for hepatocellular carcinoma, especially when hepatitis B infection is present. Recent evidence suggests that aflatoxin may be an underlying determinant of stunted child growth, and may lower cell-mediated immunity, thereby increasing disease susceptibility. However, a causal relationship between aflatoxin exposure and these latter adverse health outcomes has not been established, and the biological mechanisms for these have not been elucidated, prompting further research. Furthermore, there is a dearth of information regarding the health effects of co-exposure to aflatoxin with other mycotoxins. Recent developments of biomarkers provide opportunities for important future research in this area.

Routledge International Handbook of Rural Studies.:Understanding the association between rural ethnicity and inequalities

Rural areas are facing demographic transformation. Some localities have experienced significant levels of (internal and international) immigration in recent decades. In other rural places, a shifting minority: majority ratio (arising mainly from increased minority fertility and decreases in the majority population) is altering the rural landscape. It is this context of increasingly diverse rural societies that frames this chapter. It begins by examining inequalities arising from ethnicity in a rural context. The review proceeds by identifying how different factors, including recent patterns of international migration and historical legacies of ethnic diversity, intertwine to produce multi-cultural rural areas. First of all an overview of the significance of the ‘ethnic’ label is presented, recognizing its limitations and also its usefulness. Having established this context the chapter proceeds by highlighting the way in which rural ethnic inequalities are measured and also the particular challenges of measuring rural poverty. The processes that produce inequalities among ethnic groups are examined, with particular attention on migration and space and place, but mindful of historical legacies along with economic transformations and associated recent migration patterns. Finally, the conclusion of the chapter highlights gaps and identifies areas for future research agendas.

Microbeam studies of the bystander response.

Microbeams have undergone a renaissance since their introduction and early use in the mid 60s. Recent advances in imaging, software and beam delivery have allowed rapid technological developments in microbeams for use in a range of experimental studies. The resurgence in the use of microbeams since the mid 90s has coincided with major changes in our understanding of how radiation interacts with cells. In particular, the evidence that bystander responses occur, where cells not directly irradiated can respond to irradiated neighbours, has brought about the evolution of new models of radiation response. Although these processes have been studied using a range of experimental approaches, microbeams offer a unique route by which bystander responses can be elucidated. Without exception, all of the microbeams currently active internationally have studied bystander responses in a range of cell and tissue models. Together these studies have considerably advanced our knowledge of bystander responses and the underpinning mechanisms. Much of this has come from charged particle microbeam studies, but increasingly, X-ray and electron microbeams are starting to contribute quantitative and mechanistic information on bystander effects. A recent development has been the move from studies with 2-D cell culture models to more complex 3-D systems where the possibilities of utilizing the unique characteristics of microbeams in terms of their spatial and temporal delivery will make a major impact.

Ex vivo diagnosis of lung cancer using a Raman miniprobe.

Lung cancer is the most common cause of cancer death. The conventional method of confirming the diagnosis is bronchoscopy, inspecting the airways of the patient with a fiber optic endoscope. A number of studies have shown that Raman spectroscopy can diagnose lung cancer in vitro. In this study, Raman spectra were obtained from ex vivo normal and malignant lung tissue using a minifiber optic Raman probe suitable for insertion into the working channel of a bronchoscope. Shifted subtracted Raman spectroscopy was used to reduce the fluorescence from the lung tissue. Using principal component analysis with a leave-one-out analysis, the tissues were classified accurately. This novel technique has the potential to obtain Raman spectra from tumors from patients with lung cancer in vivo.

From stress to distress: Conceptualizing the British family farming patriarchal way of life

‘Rural stress’ and ‘farming stress’ are terms that have become commonly appropriated by British health-based academic disciplines, the medical profession and social support networks, especially since the agricultural ‘crises’ of B.S.E. and Foot and Mouth Disease. Looking beyond the media headlines, it is apparent that the terms in fact are colloquial catch-alls for visible psychological and physiological outcomes shown by individuals. Seldom have the underlying causes and origins of presentable medical outcomes been probed, particularly within the context of the patriarchal and traditionally patrilineal way of life which family forms of farming business activity in Britain encapsulate. Thus, this paper argues that insufficient attention has been paid to the conceptualization of the terms. They have become both over-used and ill-defined in their application to British family farm individuals and their life situations. A conceptual framework is outlined that attempts to shift the stress research agenda into the unilluminated spaces of the family farming ‘way of life’ and focus instead on ‘distress’. Drawing upon theorization from agricultural and feminist geography together with cultural approaches from rural geography, four distinct clusters of distress originate from the thoughts of individuals and the social practices now required to enact patriarchal family farming gender identities. These are explored using case study evidence from ethnographic repeated life history interviews with members of seven farming families in Powys, Mid Wales, an area dominated by family forms of farming business. Future research agendas need to be based firmly on the distressing reality of patriarchal family farming and also be inclusive of those who, having rejected the associated way of life, now lie beyond the farm gate.

Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies

OBJECTIVE - The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders.
RESEARCH DESIGN AND METHODS - Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies.
RESULTS - Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I 2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS - There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.

Early Childhood Development of Late-Preterm Infants: A Systematic Review

CONTEXT: Late-preterm infants (LPIs) born at 34 to 36 weeks' gestation are increasingly regarded as being at risk for adverse developmental outcomes. To date, the early childhood development of LPIs has not been systematically considered.

OBJECTIVE: To undertake a broad examination of literature relating to early childhood development at the ages of 1 to 7 years of LPIs born at 34 to 36 weeks' gestation.

METHODS: We conducted a systematic review of early childhood outcomes in LPIs by using 9 electronic databases (January 1980 to March 2010). Bibliographies were reviewed. After examination of abstracts, ineligible studies were excluded. A specifically designed data-extraction form was used. The methodologic quality of included studies was assessed by using well-documented quality-appraisal guidelines.

RESULTS: Of 4581 studies, 10 (3 prospective and 7 retrospective cohort) were included. Studies were heterogeneous, and poorer outcomes were reported among LPIs in relation to neurodevelopmental disabilities, educational ability, early-intervention requirements, medical disabilities, and physical growth in comparison to term-born children. No identified study used healthy nonadmitted LPIs as a comparison group for admitted LPIs.

CONCLUSIONS: Evidence suggests that LPIs are at increased risk of adverse developmental outcomes and academic difficulties up to 7 years of age in comparison to term infants. An infant control group matched for gestational age has not been used; thus, for LPIs, the effect of neonatal admission on longer-term outcomes has not been fully explored. Systematic measurement of early childhood outcomes is lacking, and focused long-term follow-up studies are needed to investigate early childhood development after late-preterm birth. Pediatrics 2011;127:1111-1124

Meta-analysis of 32 genome-wide linkage studies of schizophrenia

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P-SR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. Molecular Psychiatry (2009) 14, 774-785; doi:10.1038/mp.2008.135; published online 30 December 2008

On the function of the internal cavity of histone deacetylase protein 8: R37 is a crucial residue for catalysis

Biochemical studies reveal that a conserved arginine residue (R37) at the centre of the 14 angstrom internal cavity of histone deacetylase (HDAC) 8 is important for catalysis and acetate affinity. Computational studies indicate that R37 forms multiple hydrogen bonding interactions with the backbone carbonyl oxygen atoms of two conserved glycine residues, G303 and G305, resulting in a 'closed' form of the channel. One possible rationale for these data is that water or product (acetate) transit through the catalytically crucial internal channel of HDAC8 is regulated by a gating interaction between G139 and G303 tethered in position by the conserved R37. (C) 2011 Elsevier Ltd. All rights reserved.

Birth order and childhood type 1 diabetes risk: A pooled analysis of 31 observational studies

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results: Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second-or later born children became apparent [fully adjusted OR=0.90 95% confidence interval (CI) 0.83-0.98; P=0.02] but this association varied markedly between studies (I 2=67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children <5years of age (n=25 studies, maternal age adjusted OR=0.84 95% CI 0.75, 0.93; I 2=23%). Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged <5 years. This finding could reflect increased exposure to infections in early life in later born children. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.