Comparison of two methods based on cross-sectional data for correcting corpus uterine cancer incidence and probabilities

BACKGROUND: Two methods are presented for obtaining hysterectomy prevalence corrected estimates of invasive cancer incidence rates and probabilities of the corpus uterine. METHODS: The first method involves cross-sectional hysterectomy data from the Utah Hospital Discharge Data Base and mortality data applied to life-table methods. The second involves hysterectomy prevalence estimates obtained directly from the Utah Behavior Risk Factor Surveillance System (BRFSS) survey. RESULTS: Hysterectomy prevalence estimates based on the first method are lower than those obtained from the second method through age 74, but higher in the remaining ages. Correction for hysterectomy prevalence is greatest among women ages 75–79. In this age group, the uncorrected rate is 125 (per 100,000) and the corrected rate based on the life-table method is 223 using 1995–97 data, 243 using 1992–94 data, and 228 from the survey method. The uncorrected lifetime probability of developing corpus uterine cancer is 2.6%; the corrected probability from the life-table method using 1995–97 data is 4.2%, using 1992–94 data is 4.5%; and based on prevalence data from the survey method is 4.6%. CONCLUSIONS: Both methods provide reasonable hysterectomy prevalence estimates for correcting corpus uterine cancer rates and probabilities. Because of declining trends in hysterectomy in recent decades, corrected estimates from the life-table method are less pronounced than those based on the survey method. These methods may be useful for obtaining corrected uterine cancer rates and probabilities in areas of the world that do not have sufficient years of hysterectomy data to directly compute prevalence

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

<p>Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.</p> <p>Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.</p> <p>Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.</p> <p>Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.</p&gt

Biopsychosocial predictors of perceived life expectancy in a national sample of older men and women.

Perceived life expectancy (PLE) is predictive of mortality risk in older adults, but the factors that may contribute to mental conceptions of PLE are unknown. We aimed to describe the sociodemographic, biomedical, behavioral, and psychological predictors of self-reported PLE estimates among older English adults. Data were from 6662 adults aged 50-79 years in the population-based English Longitudinal Study of Ageing (cross-sectional sample from 2012/13). PLE was assessed in the face-to-face study interview ("What are the chances you will live to be age x or more?" where x = current age plus 10-15 years). Responses were categorized as 'low' (0-49%), 'medium' (50-74%), and 'high' (75-100%). Adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for low vs. high PLE were estimated using population-weighted modified Poisson regression with robust error variance. Overall, 1208/6662 (18%) participants reported a low PLE, 2806/6662 (42%) reported a medium PLE, and 2648/6662 (40%) reported a high PLE. The predictors of reporting a low PLE included older age (PR = 1.64; 95% CI: 1.50-1.76 per 10 years), male sex (PR = 1.14; 95% CI: 1.02-1.26), being a smoker (PR = 1.39; 95% CI: 1.22-1.59 vs. never/former smoker), and having a diagnosis of cancer or diabetes. A low sense of control over life was associated with low PLE, as was low satisfaction with life and worse self-rated health. Those with a higher perceived social standing were less likely to report a low PLE (PR = 0.90; 95% CI: 0.87-0.93 per 10-point increase, out of 100). This study provides novel insight into potential influences on older adults' expectations of their longevity, including aspects of psychological well-being. These results should be corroborated to better determine their implications for health-related decision-making, planning, and behavior among older adults

Linking marine phytoplankton emissions, meteorological processes, and downwind particle properties with FLEXPART

Marine biogenic particle contributions to atmospheric aerosol concentrations are not well understood though they are important for determining cloud optical and cloud-nucleating properties. Here we examine the relationship between marine aerosol measurements (with satellites and model fields of ocean biology) and meteorological variables during the North Atlantic Aerosols and Marine Ecosystems Study (NAAMES). NAAMES consisted of four field campaigns between November 2015 and April 2018 that aligned with the four major phases of the annual phytoplankton bloom cycle. The FLEXible PARTicle (FLEX-PART) Lagrangian particle dispersion model is used to spatiotemporally connect these variables to ship-based aerosol and dimethyl sulfide (DMS) observations. We find that correlations between some aerosol measurements with satellite-measured and modeled variables increase with increasing trajectory length, indicating that biological and meteorological processes over the air mass history are influential for measured particle properties and that using only spatially coincident data would miss correlative connections that are lagged in time. In particular, the marine non-refractory organic aerosol mass correlates with modeled marine net primary production when weighted by 5 d air mass trajectory residence time (r = 0.62). This result indicates that non-refractory organic aerosol mass is influenced by biogenic volatile organic compound (VOC) emissions that are typically produced through bacterial degradation of dissolved organic matter, zooplankton grazing on marine phytoplankton, and as a by-product of photosynthesis by phytoplankton stocks during advection into the region. This is further supported by the correlation of non-refractory organic mass with 2 d residence-time-weighted chlorophyll a (r = 0.39), a proxy for phytoplankton abundance, and 5 d residence-time-weighted downward shortwave forcing (r = 0.58), a requirement for photosynthesis. In contrast, DMS (formed through biological processes in the seawater) and primary marine aerosol (PMA) concentrations showed better correlations with explanatory biological and meteorological variables weighted with shorter air mass residence times, which reflects their localized origin as primary emissions. Aerosol submicron number and mass negatively correlate with sea surface wind speed. The negative correlation is attributed to enhanced PMA concentrations under higher wind speed conditions. We hypothesized that the elevated total particle surface area associated with high PMA concentrations leads to enhanced rates of condensation of VOC oxidation products onto PMA. Given the high deposition velocity of PMA relative to submicron aerosol, PMA can limit the accumulation of secondary aerosol mass. This study provides observational evidence for connections between marine aerosols and underlying ocean biology through complex secondary formation processes, emphasizing the need to consider air mass history in future analyses

Men’s oppressive beliefs predict their breast size preferences in women

Previous studies of men’s breast size preferences have yielded equivocal findings, with studies variously indicating a preference for small, medium, or large breasts. Here, we examined the impact of men’s oppressive beliefs in shaping their female breast size ideals. British White men from the community in London, England (N = 361) viewed figures of women that rotated in 360° and varied in breast size along five levels. They then rated the figure that they found most physically attractive and also completed measures assessing their sexist attitudes and tendency to objectify women. Results showed that medium breasts were rated most frequent as attractive (32.7 %), followed by large (24.4 %) and very large (19.1 %) breasts. Further analyses showed that men’s preferences for larger female breasts were significantly associated with a greater tendency to be benevolently sexist, to objectify women, and to be hostile towards women. These results were discussed in relation to feminist theories, which postulate that beauty ideals and practices in contemporary societies serve to maintain the domination of one sex over the other

Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines

yesWe describe a novel protocol to quantitatively and simultaneously compare the chemotactic responses of cells towards different chemokines. In this protocol, droplets of agarose gel containing different chemokines are applied onto the surface of a Petri dish, and then immersed under culture medium in which cells are suspended. As chemokine molecules diffuse away from the spot, a transient chemoattractant gradient is established across the spots. Cells expressing the corresponding cognate chemokine receptors migrate against this gradient by crawling under the agarose spots towards their centre. We show that this migration is chemokine-specific; meaning that only cells that express the cognate chemokine cell surface receptor, migrate under the spot containing its corresponding chemokine ligand. Furthermore, we show that migration under the agarose spot can be modulated by selective small molecule antagonists present in the cell culture medium

Towards standardized measurement of adverse events in spine surgery: conceptual model and pilot evaluation

BACKGROUND: Independent of efficacy, information on safety of surgical procedures is essential for informed choices. We seek to develop standardized methodology for describing the safety of spinal operations and apply these methods to study lumbar surgery. We present a conceptual model for evaluating the safety of spine surgery and describe development of tools to measure principal components of this model: (1) specifying outcome by explicit criteria for adverse event definition, mode of ascertainment, cause, severity, or preventability, and (2) quantitatively measuring predictors such as patient factors, comorbidity, severity of degenerative spine disease, and invasiveness of spine surgery. METHODS: We created operational definitions for 176 adverse occurrences and established multiple mechanisms for reporting them. We developed new methods to quantify the severity of adverse occurrences, degeneration of lumbar spine, and invasiveness of spinal procedures. Using kappa statistics and intra-class correlation coefficients, we assessed agreement for the following: four reviewers independently coding etiology, preventability, and severity for 141 adverse occurrences, two observers coding lumbar spine degenerative changes in 10 selected cases, and two researchers coding invasiveness of surgery for 50 initial cases. RESULTS: During the first six months of prospective surveillance, rigorous daily medical record reviews identified 92.6% of the adverse occurrences we recorded, and voluntary reports by providers identified 38.5% (surgeons reported 18.3%, inpatient rounding team reported 23.1%, and conferences discussed 6.1%). Trained observers had fair agreement in classifying etiology of 141 adverse occurrences into 18 categories (kappa = 0.35), but agreement was substantial (kappa ≥ 0.61) for 4 specific categories: technical error, failure in communication, systems failure, and no error. Preventability assessment had moderate agreement (mean weighted kappa = 0.44). Adverse occurrence severity rating had fair agreement (mean weighted kappa = 0.33) when using a scale based on the JCAHO Sentinel Event Policy, but agreement was substantial for severity ratings on a new 11-point numerical severity scale (ICC = 0.74). There was excellent inter-rater agreement for a lumbar degenerative disease severity score (ICC = 0.98) and an index of surgery invasiveness (ICC = 0.99). CONCLUSION: Composite measures of disease severity and surgery invasiveness may allow development of risk-adjusted predictive models for adverse events in spine surgery. Standard measures of adverse events and risk adjustment may also facilitate post-marketing surveillance of spinal devices, effectiveness research, and quality improvement

Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction

Pyrosequencing-Based Comparative Genome Analysis of Vibrio vulnificus Environmental Isolates

Between 1996 and 2006, the US Centers for Disease Control reported that the only category of food-borne infections increasing in frequency were those caused by members of the genus Vibrio. The Gram-negative bacterium Vibrio vulnificus is a ubiquitous inhabitant of estuarine waters, and is the number one cause of seafood-related deaths in the US. Many V. vulnificus isolates have been studied, and it has been shown that two genetically distinct subtypes, distinguished by 16S rDNA and other gene polymorphisms, are associated predominantly with either environmental or clinical isolation. While local genetic differences between the subtypes have been probed, only the genomes of clinical isolates have so far been completely sequenced. In order to better understand V. vulnificus as an agent of disease and to identify the molecular components of its virulence mechanisms, we have completed whole genome shotgun sequencing of three diverse environmental genotypes using a pyrosequencing approach. V. vulnificus strain JY1305 was sequenced to a depth of 33×, and strains E64MW and JY1701 were sequenced to lesser depth, covering approximately 99.9% of each genome. We have performed a comparative analysis of these sequences against the previously published sequences of three V. vulnificus clinical isolates. We find that the genome of V. vulnificus is dynamic, with 1.27% of genes in the C-genotype genomes not found in the E- genotype genomes. We identified key genes that differentiate between the genomes of the clinical and environmental genotypes. 167 genes were found to be specifically associated with environmental genotypes and 278 genes with clinical genotypes. Genes specific to the clinical strains include components of sialic acid catabolism, mannitol fermentation, and a component of a Type IV secretory pathway VirB4, as well as several other genes with potential significance for human virulence. Genes specific to environmental strains included several that may have implications for the balance between self-preservation under stress and nutritional competence

Personalized medicine: new genomics, old lessons

Personalized medicine uses traditional, as well as emerging concepts of the genetic and environmental basis of disease to individualize prevention, diagnosis and treatment. Personalized genomics plays a vital, but not exclusive role in this evolving model of personalized medicine. The distinctions between genetic and genomic medicine are more quantitative than qualitative. Personalized genomics builds on principles established by the integration of genetics into medical practice. Principles shared by genetic and genomic aspects of medicine, include the use of variants as markers for diagnosis, prognosis, prevention, as well as targets for treatment, the use of clinically validated variants that may not be functionally characterized, the segregation of these variants in non-Mendelian as well as Mendelian patterns, the role of gene–environment interactions, the dependence on evidence for clinical utility, the critical translational role of behavioral science, and common ethical considerations. During the current period of transition from investigation to practice, consumers should be protected from harms of premature translation of research findings, while encouraging the innovative and cost-effective application of those genomic discoveries that improve personalized medical care