Investigation of river eutrophication as part of a low dissolved oxygen TMDL implementation

In the United States, environmentally impaired rivers are subject to regulation under total maximum daily load (TMDL) regulations that specify watershed wide water quality standards. In California, the setting of TMDL standards is accompanied by the development of scientific and management plans directed at achieving specific water quality objectives. The San Joaquin River (SJR) in the Central Valley of California now has a TMDL for dissolved oxygen (DO). Low DO conditions in the SJR are caused in part by excessive phytoplankton growth (eutrophication) in the shallow, upstream portion of the river that create oxygen demand in the deeper estuary. This paper reports on scientific studies that were conducted to develop a mass balance on nutrients and phytoplankton in the SJR. A mass balance model was developed using WARMF, a model specifically designed for use in TMDL management applications. It was demonstrated that phytoplankton biomass accumulates rapidly in a 88 km reach where plankton from small, slow moving tributaries are diluted and combined with fresh nutrient inputs in faster moving water. The SJR-WARMF model was demonstrated to accurately predict phytoplankton growth in the SJR. Model results suggest that modest reductions in nutrients alone will not limit algal biomass accumulation, but that combined strategies of nutrient reduction and algal control in tributaries may have benefit. The SJR-WARMF model provides stakeholders a practical, scientific tool for setting remediation priorities on a watershed scale

Quality Assurance and its impact on ovarian visualisation rates in the multicentre United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

OBJECTIVE: To describe the quality assurance (QA) processes and their impact on visualisation of postmenopausal ovaries in the ultrasound arm of a multicentre ovarian cancer screening trial. METHODS: In UKCTOCS, 50,640 women aged 50-74 at recruitment were randomised to the ultrasound arm and underwent annual transvaginal scans. QA processes were developed during the course of the trial and included regular monitoring of Visualisation Rate (VR) of right ovary. Non-subjective factors previously identified as impacting on VR of right ovary were included in a generalised estimating equation(GEE) model for binary outcomes to enable comparison of observed versus adjusted VR between individual sonographers who had undertaken >1000scans on trial /centres. Analysis of annual VR of sonographers / centres was undertaken. RESULTS: Between June 2001 and December 2010, across 13 centres, 48230 (of 50639) women attended for 270035 annual transvaginal scans. One or both ovaries were seen in 84.5% (228145/270035) of scans. The observed VR of the right ovary was 72.7% (196426/270035). For the 78 sonographers included in the model, the median difference between observed and adjusted VR was 2% (range 0-8%) and median change in rank was 3 (range 0-18). For the 13 centres, the median difference between observed versus adjusted VR was 0% (range 0-2%) with no change in ranking. The median adjusted VR for sonographers was 73% (IQR 65-82%) and for centres was 74.7% (IQR 67.1-79.0%). Despite increasing age of the cohort, there was a steady decrease in the number of sonographers with VR80% (14.3% in 2002 to 40.8 % in 2010). Median centre VR increased from 65.5% (range 55.7-81.0%) in 2001 to 80.3% (range74.5%-90.9%) in 2010. CONCLUSIONS: A robust QA programme can improve visualisation of postmenopausal ovaries and is an essential component of ultrasound-based ovarian cancer screening trials. While VR should be adjusted for non-subjective factors that impact on ovarian visualisation, subjective factors are likely to be the largest contributors to VR differences

Does Forced Voting Result in Political Polarization?

This paper estimates the effects of the compulsory voting laws on individuals´ political orientations though a regression discontinuity framework. The identification comes from Brazil´s dual voting system – voluntary and compulsory – whose exposure is determined based on citizens’ dates of birth. Using self-collected data, we find that compulsory voting has sizable effects on individuals´ political preferences, making them more likely to identify with a political party and to become oriented towards ideological extremes

Narcissism and prosocial behavior

There are many motivations for prosocial behavior, some more altruistic and some more egoistic. We posit that more narcissistic people may perform prosocial acts strategically, for example, to improve their reputations or to receive something in return

Outcome of risk-reducing salpingo-oophorectomy in BRCA carriers and women of unknown mutation status

ObjectiveTo compare surgical outcomes and occult cancer rates at risk-reducing salpingo-oophorectomy in BRCA carriers and high-risk women who had not undergone genetic testing.DesignProspective cohort study.SettingTertiary high-risk familial gynaecological cancer clinic.PopulationWomen undergoing risk-reducing salpingo-oophorectomy between January 2005 and November 2009.MethodsWomen at high-risk of ovarian/tubal cancer were identified on the basis of the inclusion criteria for the UK Familial Ovarian Cancer Screening Study. Risk management options discussed with 1456 high-risk women included risk-reducing salpingo-oophorectomy. A strict histopathological protocol with serial slicing was used to assess tubes and ovaries.ResultsIn total, 308 high-risk women (191 with unknown mutation status; 117 known BRCA1/BRCA2 carriers) chose risk-reducing surgery; 94.5% of procedures were performed laparoscopically. The surgical complication rate was 3.9% (95% CI 2.0-6.7). Four ovarian and ten tubal occult invasive/in situ cancers were found. The overall occult invasive cancer rate was 5.1% (95% CI 1.9-10.83) in BRCA1/BRCA2 carriers and 1.05% (95% CI 0.13-3.73) in untested women. When tubal in situ cancers were included, the overall rate was 4.55% (95% CI 2.5-7.5). Two untested women with tubal carcinoma in situ were subsequently found to be BRCA carriers. The median ages of BRCA carriers (58 years; IQR 13.4 years) and untested women (49.5 years; IQR 20.6 years) with occult invasive/in situ cancer were not significantly different (P = 0.454).ConclusionsBoth high-risk women of unknown mutation status and BRCA carriers have a significant (although higher in the latter group) rate of occult invasive/in situ tubal/ovarian cancer, with a similar age distribution at detection. The data has important implications for counselling high-risk women on the likelihood of occult malignancy and perioperative complications at risk-reducing salpingo-oophorectomy. Women with occult disease should be offered genetic testing

Metabolism and Toxicity of Thioacetamide and Thioacetamide SOxide in Rat Hepatocytes

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3002719The hepatotoxicity of thioacetamide (TA) has been known since 1948. In rats, single doses cause centrilobular necrosis accompanied by increases in plasma transaminases and bilirubin. To elicit these effects TA requires oxidative bioactivation leading first to its S-oxide (TASO) and then to its chemically reactive S,S-dioxide (TASO2) which ultimately modifies amine-lipids and proteins. To generate a suite of liver proteins adducted by TA metabolites for proteomic analysis, and to reduce the need for both animals and labeled compounds, we treated isolated hepatocytes directly with TA. Surprisingly, TA was not toxic at concentrations up to 50 mM for 40 hr. On the other hand, TASO was highly toxic to isolated hepatocytes as indicated by LDH release, cellular morphology and vital staining with Hoechst 33342/propidium iodide. TASO toxicity was partially blocked by the CYP2E1 inhibitors diallyl sulfide and 4-methylpyrazole, and was strongly inhibited by TA. Significantly, we found that hepatocytes produce TA from TASO relatively efficiently by back-reduction. The covalent binding of [14C]-TASO is inhibited by unlabeled TA which acts as a “cold-trap” for [14C]-TA and prevents its re-oxidation to [14C]-TASO. This in turn increases the net consumption of [14C]-TASO despite the fact that its oxidation to TASO2 is inhibited. The potent inhibition of TASO oxidation by TA, coupled with the back-reduction of TASO and its futile redox cycling with TA may help explain phenomena previously interpreted as “saturation toxicokinetics” in the in vivo metabolism and toxicity of TA and TASO. The improved understanding of the metabolism and covalent binding of TA and TASO facilitates the use of hepatocytes to prepare protein adducts for target protein identification

Acyclovir for treating varicella in otherwise healthy children and adolescents: a systematic review of randomised controlled trials

BACKGROUND: Acyclovir has the potential to shorten the course of chickenpox which may result in reduced costs and morbidity. We conducted a systematic review of randomised controlled trials that evaluated acyclovir for the treatment of chickenpox in otherwise healthy children. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched. The reference lists of relevant articles were examined and primary authors and Glaxo Wellcome were contacted to identify additional trials. Two reviewers independently screened studies for inclusion, assessed study quality using the Jadad scale and allocation concealment, and extracted data. Continuous data were converted to a weighted mean difference (WMD). Overall estimates were not calculated due to differences in the age groups studied. RESULTS: Three studies were included. Methodological quality was 3 (n = 2) and 4 (n = 1) on the Jadad scale. Acyclovir was associated with a significant reduction in the number of days with fever, from -1.0 (95% CI -1.5,-0.5) to -1.3 (95% CI -2.0,-0.6). Results were inconsistent with respect to the number of days to no new lesions, the maximum number of lesions and relief of pruritis. There were no clinically important differences between acyclovir and placebo with respect to complications or adverse effects. CONCLUSION: Acyclovir appears to be effective in reducing the number of days with fever among otherwise healthy children with chickenpox. The results were inconsistent with respect to the number of days to no new lesions, the maximum number of lesions and the relief of itchiness. The clinical importance of acyclovir treatment in otherwise healthy children remains controversial

The incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage, 1998–2003

BACKGROUND: The authors sought to monitor the impact of widespread varicella vaccination on the epidemiology of varicella and herpes zoster. While varicella incidence would be expected to decrease, mathematical models predict an initial increase in herpes zoster incidence if re-exposure to varicella protects against reactivation of the varicella zoster virus. METHODS: In 1998–2003, as varicella vaccine uptake increased, incidence of varicella and herpes zoster in Massachusetts was monitored using the random-digit-dial Behavioral Risk Factor Surveillance System. RESULTS: Between 1998 and 2003, varicella incidence declined from 16.5/1,000 to 3.5/1,000 (79%) overall with ≥66% decreases for all age groups except adults (27% decrease). Age-standardized estimates of overall herpes zoster occurrence increased from 2.77/1,000 to 5.25/1,000 (90%) in the period 1999–2003, and the trend in both crude and adjusted rates was highly significant (p < 0.001). Annual age-specific rates were somewhat unstable, but all increased, and the trend was significant for the 25–44 year and 65+ year age groups. CONCLUSION: As varicella vaccine coverage in children increased, the incidence of varicella decreased and the occurrence of herpes zoster increased. If the observed increase in herpes zoster incidence is real, widespread vaccination of children is only one of several possible explanations. Further studies are needed to understand secular trends in herpes zoster before and after use of varicella vaccine in the United States and other countries