922 research outputs found

    P2X receptors: epithelial ion channels and regulators of salt and water transport.

    Get PDF
    When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

    Principles of Stakes Fairness in Sport

    Get PDF
    Fairness in sport is not just about assigning the top prizes to the worthiest competitors. It is also about the way the prize structure itself is organised. For many sporting competitions, although it may be acceptable for winners to receive more than losers, it can seem unfair for winners to take everything and for losers to get nothing. Yet this insight leaves unanswered some difficult questions about what stakes fairness requires and which principles of stakes fairness are appropriate for particular competitions. In this article I specify a range of different principles of stakes fairness (ten in total) that could regulate sporting competitions. I also put forward a theoretical method for pairing up appropriate principles of stakes fairness with given sporting competitions. Specifically, I argue that the underlying rationales for holding sporting competitions can provide useful guides for identifying appropriate principles of stakes fairness. I then seek to clarify and work through some of the implications of this method for a sample of real world controversies over sporting prize structures. I also attempt to refine the method in response to two possible objections from indeterminacy and relativism. Finally, I compare and contrast my conclusions with more general philosophical debates about justice

    Exposures among Pregnant Women near the World Trade Center Site on 11 September 2001

    Get PDF
    We have characterized environmental exposures among 187 women who were pregnant, were at or near the World Trade Center (WTC) on or soon after 11 September 2001, and are enrolled in a prospective cohort study of health effects. Exposures were assessed by estimating time spent in five zones around the WTC and by developing an exposure index (EI) based on plume reconstruction modeling. The daily reconstructed dust levels were correlated with levels of particulate matter ≤ 2.5 μm in aerodynamic diameter (PM(2.5); r = 0.68) or PM(10) (r = 0.73–0.93) reported from 26 September through 8 October 2001 at four of six sites near the WTC whose data we examined. Biomarkers were measured in a subset. Most (71%) of these women were located within eight blocks of the WTC at 0900 hr on 11 September, and 12 women were in one of the two WTC towers. Daily EIs were determined to be highest immediately after 11 September and became much lower but remained highly variable over the next 4 weeks. The weekly summary EI was associated strongly with women’s perception of air quality from week 2 to week 4 after the collapse (p < 0.0001). The highest levels of polycyclic aromatic hydrocarbon–deoxyribonucleic acid (PAH-DNA) adducts were seen among women whose blood was collected sooner after 11 September, but levels showed no significant associations with EI or other potential WTC exposure sources. Lead and cobalt in urine were weakly correlated with ∑EI, but not among samples collected closest to 11 September. Plasma OC levels were low. The median polychlorinated biphenyl level (sum of congeners 118, 138, 153, 180) was 84 ng/g lipid and had a nonsignificant positive association with ∑EI (p > 0.05). 1,2,3,4,6,7,8-Heptachlorodibenzodioxin levels (median, 30 pg/g lipid) were similar to levels reported in WTC-exposed firefighters but were not associated with EI. This report indicates intense bystander exposure after the WTC collapse and provides information about nonoccupational exposures among a vulnerable population of pregnant women

    Antarctic-wide array of high-resolution ice core records reveals pervasive leadpollution began in 1889 and persists today

    Get PDF
    Interior Antarctica is among the most remote places on Earth and was thought to be beyond the reach of human impacts when Amundsen and Scott raced to the South Pole in 1911. Here we show detailed measurements from an extensive array of 16 ice cores quantifying substantial toxic heavy metal lead pollution at South Pole and throughout Antarctica by 1889 – beating polar explorers by more than 22 years. Unlike the Arctic where lead pollution peaked in the 1970s, lead pollution in Antarctica was as high in the early 20th century as at any time since industrialization. The similar timing and magnitude of changes in lead deposition across Antarctica, as well as the characteristic isotopic signature of Broken Hill lead found throughout the continent, suggest that this single emission source in southern Australia was responsible for the introduction of lead pollution into Antarctica at the end of the 19th century and remains a significant source today. An estimated 660 t of industrial lead have been deposited over Antarctica during the past 130 years as a result of mid-latitude industrial emissions, with regional-to-global scale circulation likely modulating aerosol concentrations. Despite abatement efforts, significant lead pollution in Antarctica persists into the 21st century

    HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

    Get PDF
    Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group

    Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-<it>p</it>-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.</p> <p>Methods</p> <p>Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.</p> <p>Results</p> <p>The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the sum of PCBs decreased for six of eight women. During this nine year period, larger decreases in serum TEQs and PCBs were found in women with greater increases in body mass index.</p> <p>Conclusions</p> <p>This study provides suggestive evidence that average serum concentrations of dioxins, furans, and PCBs are decreasing over time among residents of this town.</p

    Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations

    Get PDF
    BACKGROUND: The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers. METHOD: In study populations of 3161 adults, comprising Greenlandic Inuits, Swedish fishermen and their wives, and inhabitants from Warsaw, Poland and Kharkiv, Ukraine, serum concentrations of CB-153 and p,p'-DDE, were analysed by gas chromatography-mass spectrometry. RESULTS: The median serum concentrations of CB-153 were for male and female Inuits 200 and 110, for Swedish fishermen 190 and their wives 84, for Kharkiv men and women 44 and 27, and for Warsaw men and women 17 and 11 ng/g lipids, respectively. The median serum concentrations of p,p'-DDE were for Kharkiv men and women 930 and 650, for male and female Inuits 560 and 300, for Warsaw men and women 530 and 380, and for Swedish fishermen 240 and their wives 140 ng/g lipids, respectively. The correlation coefficients between CB-153 and p,p'-DDE varied between 0.19 and 0.92, with the highest correlation among Inuits and the lowest among men from Warsaw. Men had averagely higher serum concentrations of CB-153 and p,p'-DDE, and there were positive associations between age and the POP-biomarkers, whereas the associations with BMI and smoking were inconsistent. Dietary seafood was of importance only in the Inuit and Swedish populations. CONCLUSION: CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations
    corecore