Early cancer detection among rural and urban californians

BACKGROUND: Since the stage of cancer detection generally predicts future mortality rates, a key cancer control strategy is to increase the proportion of cancers found in the early stage. This study compared stage of detection for members of rural and urban communities to determine whether disparities were present. METHODS: The California Cancer Registry (CCR), a total population based cancer registry, was used to examine the proportion of early stage presentation for patients with breast, melanoma, and colon cancer from 1988 to 2003. Cancer stage at time of detection for these cancers was compared for rural and urban areas. RESULTS: In patients with breast cancer, there were significantly more patients presenting at early stage in 2003 compared to 1988, but no difference in the percentage of patients presenting with early stage disease between rural and urban dwellers. There were no differences in incidence in early stage cancer incidence between these groups for melanoma patients, as well. In colorectal cancer in 1988, significantly more patients presented with early stage disease in the urban areas (42% vs 34%, p < 0.02). However, over time the rural patients were diagnosed with early stage disease with the same frequency in 2003 as 1988. CONCLUSION: This analysis demonstrates that people in rural and urban areas have their breast, melanoma or colorectal cancers diagnosed at similar stages. Health care administrators may take this information into account in future strategic planning

ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.

Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP p = 2.831 × 10-9). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic β-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 β-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in β-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations

Fashioning Entitlements: A Comparative Law and Economic Analysis of the Judicial Role in Environmental Centralization in the U.S. and Europe

This paper identifies and evaluates, from an economic point of view, the role of the judiciary the steady shift of environmental regulatory authority to higher, more centralized levels of government in both the U.S. and Europe. We supply both a positive analysis of how the decisions made by judges have affected the incentives of both private and public actors to pollute the natural environment, and normative answers to the question of whether judges have acted so as to create incentives that move levels of pollution in an efficient direction, toward their optimal, cost-minimizing (or net-benefit-maximizing) levels. Highlights of the analysis include the following points: 1) Industrial-era local (state or national) legislation awarding entitlements to pollute was almost certainly inefficient due to a fundamental economic obstacle faced by those who suffer harm from the over-pollution of publicly owned natural resources: the inability to monetize and credibly commit to repay the future economic value of reducing pollution. 2) When industrial era pollution spilled across state lines in the US, the federal courts, in particular the Supreme Court, fashioned a federal common law of interstate nuisance that set up essentially the same sort of blurry, uncertain entitlements to pollute or be free of pollution that had been created by the state courts in resolving local pollution disputes. We argue that for the typical pollution problem, a legal regime of blurry interstate entitlements - with neither jurisdiction having a clear right either to pollute or be free of pollution from the other - is likely to generate efficient incentives for interjursidictional bargaining, even despite the public choice problems besetting majority-rule government. Interestingly, a very similar system of de facto entitlements arose and often stimulated interjursidictional bargaining in Europe as well as in the U.S. 3) The US federal courts have generally interpreted the federal environmental statutes in ways that give clear primacy to federal regulators. Through such judicial interpretation, state and local regulators face a continuing risk of having their decisions overridden by federal regulators. This reduces the incentives for regulatory innovation at the state and local level. Judicial authorization of federal overrides has thus weakened the economic rationale for cooperative federalism suggested by economic models of principal-agent relationships. As a result of the principle of attribution, there is less risk in Europe that (like in the US) courts would enlarge the federal purview and thereby limit the powers of the Member States. Despite this principle, the power of the European bureaucracy (that is, the European Commission) has steadily increased and led to a steady shift of environmental regulatory competencies to the European level. This shift is only sometimes normatively desirable, and yet there is little that the ECJ can or will do to slow it

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes

Purpose Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy. Methods Results A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts. Five hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 x 10(-9). Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values = 7.41 x 10(-8) and 1.23 x 10(-8), respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p = 0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p = 0.429). Conclusion This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.Peer reviewe

A genome‐wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes

PurposeDiabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy.MethodsA genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme&nbsp;or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts.ResultsFive hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05&nbsp;×&nbsp;10-9 . Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values&nbsp;=&nbsp;7.41&nbsp;×&nbsp;10-8 and 1.23&nbsp;×&nbsp;10-8 , respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p&nbsp;=&nbsp;0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p&nbsp;=&nbsp;0.429).ConclusionThis genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene