High Resolution Determination of Nanomolar Concentrations of Dissolved Reactive Phosphate in Ocean Surface Waters Using Long Path Liquid Waveguide Capillary Cells (LWCC) and Spectrometric Detection

In the last decade, long path length, low volume, liquid waveguide capillary cells (LWCC) in conjunction with conventional nutrient auto-analyzers have been applied to determinations of nanomolar levels of phosphate, nitrate, and nitrite in oligotrophic waters. This article reports a high resolution, real-time, continuous method for nanomolar dissolved reactive phosphate measurements in ocean surface waters with data logging every 30 seconds for up to 16 consecutive hours. Surface seawater is pumped continuously from a shipboard underway tow-fish unit to a helium gas-segmented, continuous-flow, nutrient auto-analyzer modified with a 250 cm LWCC. To circumvent baseline instability due to reagents, a parallel channel with deionized water (DI) and reagents is run and later subtracted from the sample absorbances. The detection limit is 0.8 nmol/L. The precision (as relative standard deviation) at 5 nmol/L phosphate is 6.1% (n = 5) and 0.8% (n = 5) at 50 nmol/L. We also report an optimized method for discrete samples using a 200 cm LWCC. To minimize any background phosphate concentration in low nutrient seawater used as wash water solution, we use DI water, but increase sample and wash times to achieve plateau-shaped peaks after the transient wash/sample mixing period. The detection limit is 0.5 nmol/L. The precision at 10 nmol/L phosphate is 1.8% (n = 8) and 0.9% (n = 9) at 60 nmol/L. The two systems have successfully been deployed on the U.S. GEOTRACES 2010 cruise, transecting the upwelling area northwest of Africa and the highly stratified, oligotrophic, subtropical North Atlantic gyre

Arsenic and Phosphorus Biogeochemistry in the Ocean: Arsenic Species as Proxies for P-Limitation

Arsenic and phosphorus are biochemically very similar, and hence arsenate (As5+) is toxic by interfering with the energy metabolism, in particular during P limitation. However, many phytoplankton detoxify As by reducing arsenate to arsenite (As3+), and/or methylating it to mono and dimethyl As. Such As detoxification becomes operative in oligotrophic waters when phosphate concentrations are below those for As; therefore, we evaluated the potential use of these detoxification products as indicators of P-limitation by measuring As speciation during the US GEOTRACES North Atlantic transect. The distribution of As3+ concentrations in surface waters is similar to that of N : P ratios and alkaline phosphatase activity (APA), two conventional proxies for P-limitation. As3+ concentrations have a very similar relationship to phosphate as APA to phosphate, and therefore indicate the potential of As3+ as proxy for P-limitation. From the relationship to phosphate we derived threshold values of As3+ concentration to indicate moderate and extreme P-limitation. We then applied these threshold values to assess P-limitation with high horizontal resolution in the North Atlantic, improving on the contradictory assessments using the conventional proxies. Our new evaluation is consistent with the general concept that the North Atlantic is moderately to extremely limited in phosphate

The association between socioeconomic status and disability after stroke: Findings from the Adherence eValuation After Ischemic stroke Longitudinal (AVAIL) registry

Background Stroke is the leading cause of disability among adults in the United States. The association of patients’ pre-event socioeconomic status (SES) with post-stroke disability is not well understood. We examined the association of three indicators of SES—educational attainment, working status, and perceived adequacy of household income—with disability 3-months following an acute ischemic stroke. Methods We conducted retrospective analyses of a prospective cohort of 1965 ischemic stroke patients who survived to 3 months in the Adherence eValuation After Ischemic stroke – Longitudinal (AVAIL) study. Multivariable logistic regression was used to examine the relationship of level of education, pre-stroke work status, and perceived adequacy of household income with disability (defined as a modified Rankin Scale of 3–5 indicating activities of daily living limitations or constant care required). Results Overall, 58% of AVAIL stroke patients had a high school or less education, 61% were not working, and 27% perceived their household income as inadequate prior to their stroke. Thirty five percent of patients were disabled at 3-months. After adjusting for demographic and clinical factors, stroke survivors who were unemployed or homemakers, disabled and not-working, retired, less educated, or reported to have inadequate income prior to their stroke had a significantly higher odds of post-stroke disability. Conclusions In this cohort of stroke survivors, socioeconomic status was associated with disability following acute ischemic stroke. The results may have implications for public health and health service interventions targeting stroke survivors at risk of poor outcomes

An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa

BackgroundDespite the severe impact of HIV in sub-Saharan Africa, the health of older people aged 50+ is often overlooked owing to the dearth of data on the direct and indirect effects of HIV on older people's health status and well-being. The aim of this study was to examine correlates of health and well-being of HIV-infected older people relative to HIV-affected people in rural South Africa, defined as participants with an HIV-infected or death of an adult child due to HIV-related cause. MethodsData were collected within the Africa Centre surveillance area using instruments adapted from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample of 422 people aged 50+ participated. We compared the health correlates of HIV-infected to HIV-affected participants using ordered logistic regressions. Health status was measured using three instruments: disability index, quality of life and composite health score. ResultsMedian age of the sample was 60 years (range 50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than men to be in good functional ability. Women's adjusted odds of being in good overall health state were similarly lower than men's; while income and household wealth status were stronger correlates of quality of life. HIV-infected participants reported better functional ability, quality of life and overall health state than HIV-affected participants. Discussion and Conclusions The enhanced healthcare received as part of anti-retroviral treatment as well as the considerable resources devoted to HIV care appear to benefit the overall well-being of HIV-infected older people; whereas similar resources have not been devoted to the general health needs of HIV uninfected older people. Given increasing numbers of older people, policy and programme interventions are urgently needed to holistically meet the health and well-being needs of older people beyond the HIV-related care system. <br/

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Development and Initial Testing of the Stroke Rapid-Treatment Readiness Tool

ABSTRACTNo instruments are currently available to help health systems identify target areas for reducing door-to-needle times for the administration of intravenous tissue plasminogen activator to eligible patients with ischemic stroke. A 67-item Likert-scale survey was administered by telephone to stroke personnel at 252 U.S. hospitals participating in the “Get With The Guidelines-Stroke” quality improvement program. Factor analysis was used to refine the instrument to a four-factor 29-item instrument that can be used by hospitals to assess their readiness to administer intravenous tissue plasminogen activator within 60 minutes of patient hospital arrival

Does Cataract Surgery Alleviate Poverty? Evidence from a Multi-Centre Intervention Study Conducted in Kenya, the Philippines and Bangladesh

BACKGROUND: Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases. METHODOLOGY/PRINCIPAL FINDINGS: A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh:$16 vs $24 p = 0.004, Philippines:$24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh:$23 vs $23 p = 0.20, Philippines:$45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline. CONCLUSIONS/SIGNIFICANCE: This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals

Viral Load, Clinical Disease Severity and Cellular Immune Responses in Primary Varicella Zoster Virus Infection in Sri Lanka

BACKGROUND: In Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. T cells are believed to be important in the control of VZV replication and in the prevention of reactivation. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied. METHODOLOGY: We used IFNgamma ELISpot assays and MHC class II tetramers based on VZV gE and IE63 epitopes, together with quantitative real time PCR assays to compare the frequency and phenotype of specific T cells with virological and clinical outcomes in 34 adult Sri Lankan individuals with primary VZV infection. PRINCIPAL FINDINGS: Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p&lt;0.001) and were significantly higher in those over 25 years of age (P&lt;0.01). A significant inverse correlation was seen between the viral loads and the ex vivo IFNgamma ELISpot responses of patients (P&lt;0.001, r = -0.85). VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation. CONCLUSIONS: Overall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead