Cancer risk in childhood-onset systemic lupus

INTRODUCTION: The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). METHODS: We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. RESULTS: There were 1020 patients aged <18 at cohort entry. Most (82%) were female and Caucasian; mean age at cohort entry was 12.6 years (standard deviation (SD) = 3.6). Subjects were observed for a total of 7,986 (average 7.8) patient-years. Within this interval, only three invasive cancers were expected. However, 14 invasive cancers occurred with an SIR of 4.7, 95% confidence interval (CI) 2.6 to 7.8. Three hematologic cancers were found (two non-Hodgkin’s lymphoma, one leukemia), for an SIR of 5.2 (95% CI 1.1 to 15.2). The SIRs stratified by age group and sex, were similar across these strata. There was a trend for highest cancer occurrence 10 to 19 years after SLE diagnosis. CONCLUSIONS: These results suggest an increased cancer risk in pediatric onset SLE versus the general population. In absolute terms, this represents relatively few events. Of note, risk may be highest only after patients have transferred to adult care

What Factors Do Allied Health Take Into Account When Making Resource Allocation Decisions?

Abstract Background: Allied health comprises multiple professional groups including dietetics, medical radiation practitioners, occupational therapists, optometrists and psychologists. Different to medical and nursing, Allied health are often organized in discipline specific departments and allocate budgets within these to provide services to a range of clinical areas. Little is known of how managers of allied health go about allocating these resources, the factors they consider when making these decisions, and the sources of information they rely upon. The purpose of this study was to identify the key factors that allied health consider when making resource allocation decisions and the sources of information they are based upon. Methods: Four forums were conducted each consisting of case studies, a large group discussion and two hypothetical scenarios to elicit data. A thematic content analysis commenced during post-forum discussions of key factors by forum facilitators. These factors were then presented to an expert working party for further discussion and refinement. Transcripts were generated of all data recordings and a detailed thematic analysis was undertaken by one author to ensure coded data matched the initial thematic analysis. Results: Twelve factors affecting the decision-making of allied health managers and clinicians were identified. One of these factors was disendorsed by the expert working party. The 11 remaining factors can be considered to be key decision-making principles that should be consistently applied to resource allocation. These principles were clustered into three overarching themes of readiness, impact and appropriateness. Conclusion: Understanding these principles now means further research can be completed to more effectively integrate research evidence into health policy and service delivery, create partnerships among policy-makers, managers, service providers and researchers, and to provide support to answer difficult questions that policy-makers, managers and service providers face

Improving public health training and research capacity in Africa: a replicable model for linking training to health and socio-demographic surveillance data

Background: Research training for public health professionals is key to the future of public health and policy in Africa. A growing number of schools of public health are connected to health and socio-demographic surveillance system field sites in developing countries, in Africa and Asia in particular. Linking training programs with these sites provides important opportunities to improve training, build local research capacity, foreground local health priorities, and increase the relevance of research to local health policy. Objective: To increase research training capacity in public health programs by providing targeted training to students and increasing the accessibility of existing data. Design: This report is a case study of an approach to linking public health research and training at the University of the Witwatersrand. We discuss the development of a sample training database from the Agincourt Health and Socio-demographic Surveillance System in South Africa and outline a concordant transnational intensive short course on longitudinal data analysis offered by the University of the Witwatersrand and the University of Colorado-Boulder. This case study highlights ways common barriers to linking research and training can be overcome. Results and Conclusions: This collaborative effort demonstrates that linking training to ongoing data collection can improve student research, accelerate student training, and connect students to an international network of scholars. Importantly, the approach can be adapted to other partnerships between schools of public health and longitudinal research sites

2001 Wild Blueberry CSREES Project Reports

The 2001 edition of the Wild Blueberry CSREES Progress Reports was prepared for the Maine Wild Blueberry Commission and the University of Maine Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Effect of Wild Blueberry Products on Oxidation in Meat Based Food Systems 2. Factors Affecting the Microbial and Pesticide Residues Levels on Wild Blueberries 3. Determination of Pesticide Residue Levels in Fresh and Processed Wild Blueberries 4. Separation of Maggot-Infested Wild Blueberries in the IQF Processing Line 5. Water Use of Wild Blueberries and the Impact of Plant Water Stress on Yields 6. Survey of Stem Blight and Leaf Spot Diseases in Wild Blueberry Fields 7. IPM Strategies 8. Control Tactics for Wild Blueberry Pest Insects, 2001 9. Biology and Ecology of Blueberry Pest Insects 10. Diurnal Bee Activity and Measurement of Honeybee Field Strength 11. Effect of Foliar-applied Iron (Fe) Chelate Concentration on Leaf Iron Concentration, Wild Blueberry Growth and Yield 12. Effect of Boron Application Methods on Boron Uptake in Wild Blueberries 13. Effect of Foliar Iron and Copper Application on Growth and Yield of Wild Blueberries 14. Effect of Fertilizer Timing on Wild Blueberry Growth and Productivity 15. Effect of Foliar Copper Application on Growth and Yield of Wild Blueberries 16. Effect of Prune-year Applications of Nutri-Phitetm P or Nutri-Phitetm P+K on Growth and Yield of Wild Blueberry (Vaccinium angustifolium Ait.) 17. Effect of Soil pH on Nutrient Uptake 18. Assessment of Azafenidin for Weed Control in Wild Blueberries 19. Assessment of Rimsulfuron for Weed Control in Wild Blueberries 20. Assessment of Pendimethalin for Weed Control in Wild Blueberries 21. Evaluation and Demonstration of Techniques for Filling in Bare Spots in Wild Blueberry Fields 22. Assessment of Sprout-less Weeder for Hardwood Control in Wild Blueberries 23. Wild Blueberry Extension Education Program in 2001 24. Evaluation of Fungicide Efficacy in Wild Blueberry Fields 25. 2001 Pesticide Groundwater Survey 26. Cultural Weed Management Using Sulfur to Lower the pH 27. Wild Blueberry Web Sit

Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. RESULTS: Two SNPs at novel loci, rs112404845 (P = 3.8 × 10-8), upstream of COBL, and rs16961023 (P = 4.6 × 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. DISCUSSION: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS

Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

IMPORTANCE: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE: To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer's Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES: The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS: The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer's Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE: To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers

More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10-8) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10-8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10-2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10-2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10-3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies

Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish

BACKGROUND: Population heterogeneity may be a significant confounding factor hampering detection and verification of late onset Alzheimer's disease (LOAD) susceptibility genes. The Amish communities located in Indiana and Ohio are relatively isolated populations that may have increased power to detect disease susceptibility genes. METHODS: We recently performed a genome scan of dementia in this population that detected several potential loci. However, analyses of these data are complicated by the highly consanguineous nature of these Amish pedigrees. Therefore we applied the Combinatorial Mismatch Scanning (CMS) method that compares identity by state (IBS) (under the presumption of identity by descent (IBD)) sharing in distantly related individuals from such populations where standard linkage and association analyses are difficult to implement. CMS compares allele sharing between individuals in affected and unaffected groups from founder populations. Comparisons between cases and controls were done using two Fisher's exact tests, one testing for excess in IBS allele frequency and the other testing for excess in IBS genotype frequency for 407 microsatellite markers. RESULTS: In all, 13 dementia cases and 14 normal controls were identified who were not related at least through the grandparental generation. The examination of allele frequencies identified 24 markers (6%) nominally (p ≤ 0.05) associated with dementia; the most interesting (empiric p ≤ 0.005) markers were D3S1262, D5S211, and D19S1165. The examination of genotype frequencies identified 21 markers (5%) nominally (p ≤ 0.05) associated with dementia; the most significant markers were both located on chromosome 5 (D5S1480 and D5S211). Notably, one of these markers (D5S211) demonstrated differences (empiric p ≤ 0.005) under both tests. CONCLUSION: Our results provide the initial groundwork for identifying genes involved in late-onset Alzheimer's disease within the Amish community. Genes identified within this isolated population will likely play a role in a subset of late-onset AD cases across more general populations. Regions highlighted by markers demonstrating suggestive allelic and/or genotypic differences will be the focus of more detailed examination to characterize their involvement in dementia

Resolve and eco: the halo mass-dependent shape of galaxy stellar and baryonic mass functions

In this work, we present galaxy stellar and baryonic (stars plus cold gas) mass functions (SMF and BMF) and their halo mass dependence for two volume-limited data sets. The first, RESOLVE-B, coincides with the Stripe 82 footprint and is extremely complete down to baryonic mass Mbary ∼ 10^9.1 M⊙, probing the gas-rich dwarf regime below Mbary ∼ 10^10 M⊙. The second, ECO, covers a ~40× larger volume (containing RESOLVE-A) and is complete to Mbary ~10^9.4 M⊙. To construct the SMF and BMF we implement a new “cross-bin sampling” technique with Monte Carlo sampling from the full likelihood distributions of stellar or baryonic mass. Our SMFs exhibit the “plateau” feature starting below Mstar ~10^10 M⊙ that has been described in prior work. However, the BMF fills in this feature and rises as a straight power law below ~10^10 M⊙, as gas-dominated galaxies become the majority of the population. Nonetheless, the low-mass slope of the BMF is not as steep as that of the theoretical dark matter halo MF. Moreover, we assign group halo masses by abundance matching, finding that the SMF and BMF separated into four physically motivated halo mass regimes reveal complex structure underlying the simple shape of the overall MFs. In particular, the satellite MFs are depressed below the central galaxy MF “humps” in groups with mass < 10^13.5 M⊙ yet rise steeply in clusters. Our results suggest that satellite destruction and/or stripping are active from the point of nascent group formation. We show that the key role of groups in shaping MFs enables reconstruction of a given survey’s SMF or BMF based on its group halo mass distribution