Challenges in Collating Spirometry Reference Data for South-Asian Children: An Observational Study.

METHODS Spirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n = 110). RESULTS Following exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5-17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4-19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The 'GLI-Other' equation fitted data from North India reasonably well while 'GLI-Black' equations provided a better approximation for South-Asian data than the 'GLI-White' equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment. CONCLUSION Until improved and more robust prediction equations can be derived, we recommend the use of 'GLI-Black' equations for interpreting most South-Asian data, although 'GLI-Other' may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required.

An assessment of the nutritional status of orphaned adolescents living in Nyanza Province, Kenya

Increasing numbers of children and adolescents are becoming vulnerable or orphaned due to the HIV/AIDS epidemic in Nyanza Province, Kenya. Research indicates food security remains a top concern for those caring for these children or adolescents. This study was a examined thinness, stunting, and perceptions about food availability in adolescents ages 10-17 years in Nyanza Province. No evidence was found suggesting orphaned adolescents experience greater amounts of stunting or thinness over non-orphaned adolescents in the province. Orphans did not perceive less available food in their households. Instead, predictors of thinness, stunting, or low perceptions of food availability included age, household facilities, perceptions of equal or unequal treatment in the household, and perceptions about the household's ability to provide them with basic needs. Findings suggest interventions aimed at decreasing malnutrition focus less on orphaned versus non-orphaned adolescents, but they should focus on adolescents made vulnerable due to lower socioeconomic status. ^

Immune and genetic risk factors in glioma

Despite extensive research, the etiology of adult glioma remains largely unknown. We sought to further explore the role of immune and genetic factors in glioma etiology using data from the Harris County Brain Tumor Study and the first U.S. genome-wide association study of glioma. First, using a case-control study design, we examined the association between adult glioma risk and surrogates of the timing and frequency of common early childhood infections, birth order and sibship size, respectively. We found that each one-unit increase in birth order was associated with a 12% decreased risk of glioma development in adulthood (OR=0.88, 95% CI=0.81-0.96); however, sibship size was not associated with adult glioma risk (OR=0.96, 95% CI=0.91-1.02). Second, we used a multi-strategic approach to explore the relationships between glioma risk, history of asthma/allergies, and 23 functional SNPs in 11 inflammation genes. We found three inflammation gene SNPs to be significantly associated with glioma risk (COX2/PTGS2 rs20417 [OR=1.41]; IL10 rs1800896 [OR=1.57]; and IL13 rs20541 [OR=0.39]). Joint effects analysis of the risk-conferring alleles of these three SNPs revealed a trend of increasing risk with increasing number of adverse alleles among those without asthma/allergies (p<0.0001). Finally, we conducted a case-only study to explore pairwise SNP-SNP interactions in immune-related pathways among a population of 1304 non-Hispanic white glioma cases. After correction for multiple comparisons, we found 279 significant SNP-SNP interactions among polymorphisms of immune-related genes, many of which have not been previously examined. Our results, cumulatively, suggest an important role for immune and genetic factors in glioma etiology and provide several new hypotheses for future studies.^

Logistic regression with incompletely observed binary

Logistic regression is one of the most important tools in the analysis of epidemiological and clinical data. Such data often contain missing values for one or more variables. Common practice is to eliminate all individuals for whom any information is missing. This deletion approach does not make efficient use of available information and often introduces bias.^ Two methods were developed to estimate logistic regression coefficients for mixed dichotomous and continuous covariates including partially observed binary covariates. The data were assumed missing at random (MAR). One method (PD) used predictive distribution as weight to calculate the average of the logistic regressions performing on all possible values of missing observations, and the second method (RS) used a variant of resampling technique. Additional seven methods were compared with these two approaches in a simulation study. They are: (1) Analysis based on only the complete cases, (2) Substituting the mean of the observed values for the missing value, (3) An imputation technique based on the proportions of observed data, (4) Regressing the partially observed covariates on the remaining continuous covariates, (5) Regressing the partially observed covariates on the remaining continuous covariates conditional on response variable, (6) Regressing the partially observed covariates on the remaining continuous covariates and response variable, and (7) EM algorithm. Both proposed methods showed smaller standard errors (s.e.) for the coefficient involving the partially observed covariate and for the other coefficients as well. However, both methods, especially PD, are computationally demanding; thus for analysis of large data sets with partially observed covariates, further refinement of these approaches is needed. ^

Genetic Predictors of Clinical Outcomes in Non-Small Cell Lung Cancer Patients

Lung cancer is the leading cause of cancer-related mortality in the US. Emerging evidence has shown that host genetic factors can interact with environmental exposures to influence patient susceptibility to the diseases as well as clinical outcomes, such as survival and recurrence. We aimed to identify genetic prognostic markers for non-small cell lung cancer (NSCLC), a major (85%) subtype of lung cancer, and also in other subgroups. With the fast evolution of genotyping technology, genetic association studies have went through candidate gene approach, to pathway-based approach, to the genome wide association study (GWAS). Even in the era of GWAS, pathway-based approach has its own advantages on studying cancer clinical outcomes: it is cost-effective, requiring a smaller sample size than GWAS easier to identify a validation population and explore gene-gene interactions. In the current study, we adopted pathway-based approach focusing on two critical pathways - miRNA and inflammation pathways. MicroRNAs (miRNA) post-transcriptionally regulate around 30% of human genes. Polymorphisms within miRNA processing pathways and binding sites may influence patients’ prognosis through altered gene regulation. Inflammation plays an important role in cancer initiation and progression, and also has shown to impact patients’ clinical outcomes. We first evaluated 240 single nucleotide polymorphisms (SNPs) in miRNA biogenesis genes and predicted binding sites in NSCLC patients to determine associations with clinical outcomes in early-stage (stage I and II) and late-stage (stage III and IV) lung cancer patients, respectively. First, in 535 early-stage patients, after correcting multiple comparisons, FZD4:rs713065 (hazard ratio [HR]:0.46, 95% confidence interval [CI]:0.32-0.65) showed a significant inverse association with survival in early stage surgery-only patients. SP1:rs17695156 (HR:2.22, 95% CI:1.44-3.41) and DROSHA:rs6886834 (HR:6.38, 95% CI:2.49-16.31) conferred increased risk of progression in the all patients and surgery-only populations, respectively. FAS:rs2234978 was significantly associated with improved survival in all patients (HR:0.59, 95% CI:0.44-0.77) and in the surgery plus chemotherapy populations (HR:0.19, 95% CI:0.07-0.46).. Functional genomics analysis demonstrated that this variant creates a miR-651 binding site resulting in altered miRNA regulation of FAS, providing biological plausibility for the observed association. We then analyzed these associations in 598 late-stage patients. After multiple comparison corrections, no SNPs remained significant in the late stage group, while the top SNP NAT1:rs15561 (HR=1.98, 96%CI=1.32-2.94) conferred a significantly increased risk of death in the chemotherapy subgroup. To test the hypothesis that genetic variants in the inflammation-related pathways may be associated with survival in NSCLC patients, we first conducted a three-stage study. In the discovery phase, we investigated a comprehensive panel of 11,930 inflammation-related SNPs in three independent lung cancer populations. A missense SNP (rs2071554) in HLA-DOB was significantly associated with poor survival in the discovery population (HR: 1.46, 95% CI: 1.02-2.09), internal validation population (HR: 1.51, 95% CI: 1.02-2.25), and external validation (HR: 1.52, 95% CI: 1.01-2.29) population. Rs2900420 in KLRK1 was significantly associated with a reduced risk for death in the discovery (HR: 0.76, 95% CI: 0.60-0.96) and internal validation (HR: 0.77, 95% CI: 0.61-0.99) populations, and the association reached borderline significance in the external validation population (HR: 0.80, 95% CI: 0.63-1.02). We also evaluated these inflammation-related SNPs in NSCLC patients in never smokers. Lung cancer in never smokers has been increasingly recognized as distinct disease from that in ever-smokers. A two-stage study was performed using a discovery population from MD Anderson (411 patients) and a validation population from Mayo Clinic (311 patients). Three SNPs (IL17RA:rs879576, BMP8A:rs698141, and STK:rs290229) that were significantly associated with survival were validated (pCD74:rs1056400 and CD38:rs10805347) were borderline significant (p=0.08) in the Mayo Clinic population. In the combined analysis, IL17RA:rs879576 resulted in a 40% reduction in the risk for death (p=4.1 × 10-5 [p=0.61, heterogeneity test]). We also validated a survival tree created in MD Anderson population in the Mayo Clinic population. In conclusion, our results provided strong evidence that genetic variations in specific pathways that examined (miRNA and inflammation pathways) influenced clinical outcomes in NSCLC patients, and with further functional studies, the novel loci have potential to be translated into clinical use.

Observations from the Balcony: Directions for Pediatric Health Disparities Research and Policy

In 2002, the Institute of Medicine released Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare, a landmark monograph documenting health disparities in the U.S. health care system. Since the publication of Unequal Treatment, the field of pediatric health disparities research has advanced significantly with a proliferation of studies examining a wide array of topics concerning inequities in child health. Advances in health care policy and legislation have also added to a heightened discourse on pediatric health disparities. While there has been substantial activity in efforts to address pediatric health disparities, questions remain regarding whether these efforts have changed the trajectory of health equity among children. The aim of this paper is to examine the practical challenges of addressing pediatric health disparities in the dynamic context of global changes in health care research, policy, and legislation relevant to children. Using the Adaptive Leadership framework, this paper outlines a conceptual model for assessing the scope of progress made in addressing pediatric health disparities, diagnoses the continued adaptive challenges of pediatric health disparities, and provides an agenda for further work and future investment.

Geochemical and isotopic composition of sediments and pore waters from ODP Leg 164 sites

Authigenic carbonates were recovered from several horizons between 0 and 52 mbsf in sediments that overlay the Blake Ridge Diapir on the Carolina Rise (Ocean Drilling Program [ODP] Site 996). Active chemosynthetic communities at this site are apparently fed by fluid conduits extending beneath a bottom-simulating reflector (BSR). Gas hydrates occur at several depth intervals in these near-surface sediments. The carbonate nodules are composed of rounded to subangular intraclasts and carbonate cemented mussel shell fragments. Electron microprobe and X-ray diffraction (XRD) investigations show that aragonite is the dominant authigenic carbonate. Authigenic aragonite occurs both as microcrystalline, interstitial cement, and as cavity-filling radial fibrous crystals. The d13C values of the authigenic aragonite vary between -48.4 per mil and -30.5 per mil (Peedee belemnite [PDB]), indicating that carbon derived from 13C-depleted methane is incorporated into these carbonates. The d13C of pore water sum CO2 values are most negative in the upper 10 mbsf, near the sediment/water interface (-38 per mil ± 5 per mil), but noticeably more positive below 25 mbsf (+5 per mil ± 6 per mil). Because carbonates derive their carbon from HCO3-, dissimilarities between the d13C values of carbonate precipitates recovered from greater than 10 mbsf and d13C values of the associated pore fluids suggests that these carbonates formed near the seafloor. Differences of about 1 per mil in the oxygen isotopic composition of carbonate precipitates from different depths are possibly related to changes in bottom-water conditions during glacial and interglacial time periods. Measurements of the strontium isotopic composition on 13 carbonate samples show 87Sr/86Sr values between 0.709125 and 0.709206 with a mean of 0.709165, consistent with the approximate age of their host sediment. Furthermore, the 87Sr/86Sr values of six pore-water samples from Site 996 vary between 0.709130 and 0.709204. The similarity of these values to seawater (87Sr/86Sr = 0.709175), and to 87Sr/86Sr values of pore water from similar sample depths elsewhere on the Blake Ridge (Sites 994, 995, and 997), indicates a shallow Sr source. The 87Sr/86Sr values of the authigenic carbonates at Site 996 are not consistent with the Sr isotopic values predicted for carbonates precipitated from fluids transported upward along fault conduits extending through the base of the gas hydrate-stability zone. Based on our data, we see no evidence of continuing carbonate diagenesis with depth. Therefore, with the exception of their seafloor expression as carbonate crusts, fossil vent sites will not be preserved. Because these authigenic features apparently form only at the seafloor, their vertical distribution and sediment age imply that seepage has been going on in this area for at least 600,000 yr.

Mercado de trabajo y condicionamiento por color de piel en grandes centros urbanos de la Argentina

La discriminación por aspecto físico, y más en particular, el trato diferenciado hacia personas cuyos rasgos remiten a un origen entendido como indígena o no-europeo, constituye un problema escasamente tratado en los estudios de la desigualdad en la Argentina. Esta carencia, sumada a la falta de una articulación en las explicaciones de estos mecanismos relacionados con las desigualdades derivadas de las condiciones de clase, con frecuencia opacan el estudio del fenómeno profundizando sus efectos de invisibilidad. En este sentido, se mantienen ocultas las dificultades que afrontan quienes poseen estos rasgos para sobreponerse a prejuicios que reeditan cotidianamente principios racistas que asocian los rasgos nativos con la delincuencia, la falta de capacidades y saberes y, en términos generales, con la inferioridad socialmente entendida. En este artículo se investiga la incidencia del trato desigual basado en el aspecto físico -en particular, en el color de piel- sobre los logros laborales en una muestra de 2.500 personas de grandes centros urbanos de la Argentina en el año 2007. La discriminación por rasgos físicos, como efecto de la persistencia de principios operativos basados en la racialización de las interacciones sociales, pone de manifiesto la continuidad de principios jerárquicos, simbólicos y materiales que obstruyen la posibilidad de una mayor igualdad en el desarrollo cotidiano de las condiciones de vida de las personas

Mercado de trabajo y condicionamiento por color de piel en grandes centros urbanos de la Argentina

La discriminación por aspecto físico, y más en particular, el trato diferenciado hacia personas cuyos rasgos remiten a un origen entendido como indígena o no-europeo, constituye un problema escasamente tratado en los estudios de la desigualdad en la Argentina. Esta carencia, sumada a la falta de una articulación en las explicaciones de estos mecanismos relacionados con las desigualdades derivadas de las condiciones de clase, con frecuencia opacan el estudio del fenómeno profundizando sus efectos de invisibilidad. En este sentido, se mantienen ocultas las dificultades que afrontan quienes poseen estos rasgos para sobreponerse a prejuicios que reeditan cotidianamente principios racistas que asocian los rasgos nativos con la delincuencia, la falta de capacidades y saberes y, en términos generales, con la inferioridad socialmente entendida. En este artículo se investiga la incidencia del trato desigual basado en el aspecto físico -en particular, en el color de piel- sobre los logros laborales en una muestra de 2.500 personas de grandes centros urbanos de la Argentina en el año 2007. La discriminación por rasgos físicos, como efecto de la persistencia de principios operativos basados en la racialización de las interacciones sociales, pone de manifiesto la continuidad de principios jerárquicos, simbólicos y materiales que obstruyen la posibilidad de una mayor igualdad en el desarrollo cotidiano de las condiciones de vida de las personas

Geochemistry of ODP Site 125-786 volcanic rocks

Eocene-Oligocene volcanic rocks drilled at Site 786 in the Izu-Bonin forearc cover a wide range of compositions from primitive boninites to highly evolved rhyolites. K-Ar dating reveals at least two distinct episodes of magmatism; one at 41 Ma and a later one at 35 Ma. The early episode produced low-Ca boninites and bronzite andesites that form an oceanic basement of pillow lavas and composite intrusive sheets, overlain by flows and intrusive sheets of intermediate-Ca boninites and bronzite-andesites and a fractionated series of andesites, dacites, and rhyolites. The later episode produced high-Ca boninites and intermediate-Ca boninites, exclusively as intrusive sheets.

Mercado de trabajo y condicionamiento por color de piel en grandes centros urbanos de la Argentina

La discriminación por aspecto físico, y más en particular, el trato diferenciado hacia personas cuyos rasgos remiten a un origen entendido como indígena o no-europeo, constituye un problema escasamente tratado en los estudios de la desigualdad en la Argentina. Esta carencia, sumada a la falta de una articulación en las explicaciones de estos mecanismos relacionados con las desigualdades derivadas de las condiciones de clase, con frecuencia opacan el estudio del fenómeno profundizando sus efectos de invisibilidad. En este sentido, se mantienen ocultas las dificultades que afrontan quienes poseen estos rasgos para sobreponerse a prejuicios que reeditan cotidianamente principios racistas que asocian los rasgos nativos con la delincuencia, la falta de capacidades y saberes y, en términos generales, con la inferioridad socialmente entendida. En este artículo se investiga la incidencia del trato desigual basado en el aspecto físico -en particular, en el color de piel- sobre los logros laborales en una muestra de 2.500 personas de grandes centros urbanos de la Argentina en el año 2007. La discriminación por rasgos físicos, como efecto de la persistencia de principios operativos basados en la racialización de las interacciones sociales, pone de manifiesto la continuidad de principios jerárquicos, simbólicos y materiales que obstruyen la posibilidad de una mayor igualdad en el desarrollo cotidiano de las condiciones de vida de las personas

Acoustic multi-frequency indicator of four major groups on a spatial grid in the Bay of Biscay

The first data set contains the mean and cofficient of variation (standard deviation divided by mean) of a multi-frequency indicator I derived from ER60 acoustic information collected at five frequencies (18, 38, 70, 120, and 200 kHz) in the Bay of Biscay in May of the years 2006, 2008, 2009 and 2010 (Pelgas surveys). The multi-frequency indicator was first calculated per voxel (20 m long × 5 m deep sampling unit) and then averaged on a spatial grid (approx. 20 nm × 20 nm) for five 5-m depth layers in the surface waters (10-15m, 15-20m, 20-25m, 25-30m below sea surface); there are missing values in particular in the shallowest layer. The second data set provides for each grid cell and depth layer the proportion of voxels for which the multi-frequency indicator I was indicative of a certain group of organisms. For this the following interpretation was used: I < 0.39 swim bladder fish or large gas bubbles, I = 0.39-0.58 small resonant bubbles present in gas bearing organisms such as larval fish and phytoplankton, I = 0.7-0.8 fluidlike zooplankton such as copepods and euphausiids, and I > 0.8 mackerel. These proportions can be interpreted as a relative abundance index for each of the four organism groups.

(Table 3) Oxygen isotope ratios of benthic foraminifera from DSDP Hole 80-548

Presently, the intermediate depths of the North Atlantic Ocean are occupied by a great lens of warm, saline water whose source is the Mediterranean Sea. This water flows both westward and northward, finally entering the Norwegian Sea where it may contribute to the formation of North Atlantic Deep Water. The Late Neogene history of Mediterranean Outflow in the Atlantic can be monitored at DSDP-IPOD Site 548 on the continental slope Southwest of Ireland using benthic Foraminifera oxygen isotope values. Isotopic data from 154 samples indicate that Mediterranean water was absent from the mid-depth North Atlantic from 3.4 to 3.2 Ma ago. However, at about 2.9 Ma ago the isotopic values at Site 548 diverge from those recorded from the deep North Atlantic and they can be interpreted to indicate the appearance of a new water mass, possibly Mediterranean water, in the North Atlantic water column. This appearance may be related to climatic changes that occurred around the Mediterranean Basin at about 2.9 Ma ago. The analysis of 189 samples for grain-size distributions shows that a significant increase in the silt-size fraction occurs at the same level that isotopic analysis indicates a change in bottom waters at Site 548. The grainsize data support the hypothesis that mid-depth water-mass changes occurred at about 2.9 Ma ago.

Late Miocene carbon isotope and paleoproductivity record

We examine whether or not a relationship exists between the late Miocene carbon isotope shift (~7.6-6.6 Ma) and marine productivity at four sites from the Indian and Pacific Oceans (Ocean Drilling Program Sites 721, 1146, 1172, and 846). We use a multiproxy approach based on benthic foraminiferal accumulation rates, elemental ratios, and dissolution indices, and we compare these data to benthic foraminiferal d13C values measured on the same samples. Although some of these sites have been targeted previously in studies of either the late Miocene/early Pliocene "biogenic bloom" (Sites 721 and 846) or the late Miocene carbon isotope shift (Site 1172), our records are the first to establish paired proxy records of carbon isotopes and paleoproductivity allowing a direct assessment of a potential link. Our results indicate that at all sites, productivity increased sometime during the d13C shift; at three sites (721, 1146, and 846), productivity increased at the beginning of the shift. The correlation coefficients derived from linear regression between micropaleontologically derived productivity and foraminiferal d13C values are relatively high during the time interval containing the late Miocene d13C shift (and statistically significant at three of the sites). Carbon flux and isotope mass balance considerations illustrate that transfer of organic matter between the terrestrial and marine reservoirs together with enhanced oceanic upwelling best approximates observed changes in carbon isotope records and paleoproductivity. We note that long-term trend in the Site 846 paleoproductivity record can be correlated to the long-term trend in the Site 848 eolian flux reconstructions of Hovan (1995, doi:10.2973/odp.proc.sr.138.132.1995) hinting at a link between strengthened wind regime and productivity during the late Miocene.

Mg/Ca variability in Globigerinoides ruber tests

Laser ablation inductively coupled plasma-mass spectrometry microanalysis of fossil and live Globigerinoides ruber from the eastern Indian Ocean reveals large variations of Mg/Ca composition both within and between individual tests from core top or plankton pump samples. Although the extent of intertest and intratest compositional variability exceeds that attributable to calcification temperature, the pooled mean Mg/Ca molar values obtained for core top samples between the equator and >30°S form a strong exponential correlation with mean annual sea surface temperature (Mg/Ca mmol/mol = 0.52 exp**0.076SST°C, r**2 = 0.99). The intertest Mg/Ca variability within these deep-sea core top samples is a source of significant uncertainty in Mg/Ca seawater temperature estimates and is notable for being site specific. Our results indicate that widely assumed uncertainties in Mg/Ca thermometry may be underestimated. We show that statistical power analysis can be used to evaluate the number of tests needed to achieve a target level of uncertainty on a sample by sample case. A varying bias also arises from the presence and varying mix of two morphotypes (G. ruber ruber and G. ruber pyramidalis), which have different mean Mg/Ca values. Estimated calcification temperature differences between these morphotypes range up to 5°C and are notable for correlating with the seasonal range in seawater temperature at different sites.