The Frasnian-Famennian mass killing event(s), methods of identification and evaluation

The absence of an abnormally high number of earlier Devonian taxa from Famennian sediments was repeatedly documented and can hardly be questioned. Primary recognition of the event(s) was based on paleontological data, especially common macrofossils. Most paleontologists place the disappearance of these common forms at the gigas/triangularis contact and this boundary was recently proposed as the Frasnian-Famennian (F-F) boundary. Not unexpectedly, alternate F-F positions were suggested caused by temporary Frasnian survivors or sudden post-event radiations of new forms. Secondary supporting evidence for mass killing event(s) is supplied by trace element and stable isotope geochemistry but not with the same success as for the K/T boundary, probably due to additional 300 ma of tectonic and diagenetic overprinting. Another tool is microfacies analysis which is surprisingly rarely used even though it can explain geochemical anomalies or paleontological overlap not detectable by conventional macrofacies analysis. The combination of microfacies analysis and geochemistry was applied at two F-F sections in western Canada and showed how interdependent the two methods are. Additional F-F sections from western Canada, western United States, France, Germany and Australia were sampled or re-sampled and await geochemical/microfacies evaluation

A late Devonian impact event and its association with a possible extinction event on Eastern Gondwana

Evidence from South China and Western Australia for a 365-Ma impact event in the Lower crepida conodont zone of the Famennian stage of the Late Devonian (about 1.5 Ma after the Frasnian/Famennian extinction event) includes microtektitelike glassy microspherules, geochemical anomalies (including a weak Ir), a probable impact crater (greater than 70 k) at Taihu in South China, and an Ir anomaly in Western Australia. A brachiopod faunal turnover in South China, and the 'strangelove ocean'-like c-delta 13 excursions in both Chinese and Australian sections indicate that at least a regional-scale extinction might have occurred at the time of the impact. A paleoreconstruction shows that South China was very close to and facing Western Australia in the Late Devonian. The carbon isotopic excursions, which occur at the same stratigraphic level in both South China and Western Australia cannot be explained as being coincidental. The c-delta 13 excursions and the brachiopod faunal turnover in South China indicate that there might have been at least a regional (possibly global) extinction in the Lower crepida zone. The impact-derived microspherules and geochemical anomalies (especially the Ir) indicate a Lower crepida zone impact event on eastern Gondwana. The location, type of target rocks, and possibly age of the Taihu Lake crater qualify as the probable site of this Late Devonian impact

Increasing Coverage of Antiretroviral Therapy and Male Medical Circumcision in HIV Hyperendemic Countries: A Cost-Benefit Analysis

HIV continues to cause the largest number of disability-adjusted life years of any disease in HIV hyperendemic countries (i.e., countries with an adult HIV prevalence >15%). We compare the benefits and costs of two proven biological interventions to reduce the health losses due to the HIV epidemic in hyperendemic countries from 2015 through 2030: 1) increasing ART coverage to 90% among HIV-infected adults with a CD4-cell count <350 cells/microliter, before expanding the HIV treatment scale-up to people with higher CD4-cell counts; and 2) increasing male medical circumcision coverage to at least 90% among HIV-uninfected adult men. We developed a mathematical model to determine the benefits and costs of increasing the coverage of both ART under different CD4-cell count thresholds and of circumcision in HIV-hyperendemic countries. The results show that scaling up ART and circumcision are both cost-beneficial. However, the benefit-to-cost ratio (BCR) for circumcision is significantly higher than for ART: 7.4 vs. 3.0 (at US$1,000 per life year and a 5$5,000 per life year and a 3% discount rate). The additional cost of scaling up circumcision is approximately $US500 million while the additional cost of increasing ART coverage lies between$US17 and $US19 billion. We conclude that increasing the coverage of ART among HIV-infected adults with a CD4-cell count <350 cells/microliter and, in particular, scaling up male medical circumcision among HIV-negative men are both highly cost-beneficial interventions to reduce the health burdens resulting from the HIV epidemic in hyperendemic countries over the next 15 years

Naturally occurring autoantibodies against beta-amyloid: investigating their role in transgenic animal and in vitro models of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against β-amyloid (Aβ) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aβ (NAbs-Aβ) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-Aβ recognized the mid-/C-terminal end of Aβ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-Aβ were able to interfere with Aβ peptide toxicity, but NAbs-Aβ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-Aβ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-Aβ to dispose of proteins or peptides that are prone to forming toxic aggregates

Costs of Parkinson's Disease and Antiparkinsonian Pharmacotherapy: An Italian Cohort Study

Objective: Antiparkinsonian pharmacotherapy is costly and the determinants of drug costs in Parkinson's disease (PD) have been poorly investigated. The objective of this study was to investigate the costs of PD and antiparkinsonian drugs in an Italian cohort of patients and identify cost-driving factors of drug therapy. Methods: Seventy outpatients with idiopathic PD were recruited in the Department of Neurology, Napoli University, Italy. Data on resource utilization were collected for 6 months using a bottom-up approach. Clinical status was evaluated using the Unified Parkinson's Disease Rating Scale. Direct and indirect costs were calculated from the societal perspective (figures of year 2009). Independent determinants of total costs and costs of antiparkinsonian drugs were identified using multivariate regression analysis. Results: The total costs of PD were EUR 8,640 (95% CI: EUR 6,700-11,240) per patient over a 6-month period. Direct costs accounted for 70% of the total costs. Antiparkinsonian drugs (EUR 1,450; 95% CI: EUR 1,220-1,760) were the primary component of costs paid by the health insurance (39.6%) and one of the most expensive components of the direct costs (24.0%). The highest copayments made by patients were for antiparkinsonian drugs and medical equipment (58%). Independent determinants of the increased costs of antiparkinsonian pharmacotherapy were younger age and occurrence of motor fluctuations. Conclusions: Antiparkinsonian pharmacotherapy is one of the major cost components of PD-related costs for health insurance. It imposes a considerable economic burden on patients and their families as well. Copyright (C) 2010 S. Karger AG, Base

The role of sea-level change and marine anoxia in the Frasnian-Famennian (Late Devonian) mass extinction

Johnson et al. (Johnson, J.G., Klapper, G., Sandberg, C.A., 1985. Devonian eustatic fluctuations in Euramerica. Geological Society of America Bulletin 96, 567–587) proposed one of the first explicit links between marine anoxia, transgression and mass extinction for the Frasnian–Famennian (F–F, Late Devonian) mass extinction. This cause-and-effect nexus has been accepted by many but others prefer sea-level fall and cooling as an extinction mechanism. New facies analysis of sections in the USA and Europe (France, Germany, Poland), and comparison with sections known from the literature in Canada, Australia and China reveal several high-frequency relative sea-level changes in the late Frasnian to earliest Famennian extinction interval. A clear signal of major transgression is seen within the Early rhenana Zone (e.g. drowning of the carbonate platform in the western United States). This is the base of transgressive–regressive Cycle IId of the Johnson et al. (Johnson, J.G., Klapper, G., Sandberg, C.A., 1985. Devonian eustatic fluctuations in Euramerica. Geological Society of America Bulletin 96, 567–587) eustatic curve. This was curtailed by regression and sequence boundary generation within the early linguiformis Zone, recorded by hardground and karstification surfaces in sections from Canada to Australia. This major eustatic fall probably terminated platform carbonate deposition over wide areas, especially in western North America. The subsequent transgression in the later linguiformis Zone, recorded by the widespread development of organic-rich shale facies, is also significant because it is associated with the expansion of anoxic deposition, known as the Upper Kellwasser Event. Johnson et al.'s (Johnson, J.G., Klapper, G., Sandberg, C.A., 1985. Devonian eustatic fluctuations in Euramerica. Geological Society of America Bulletin 96, 567–587) original transgression-anoxia–extinction link is thus supported, although some extinction losses of platform carbonate biota during the preceeding regression cannot be ruled out. Conodont faunas suffered major losses during the Upper Kellwasser Event, with deep-water taxa notably affected. This renders unreliable any eustatic analyses utilising changes in conodont biofacies. Claims for a latest Frasnian regression are not supported, and probably reflect poor biostratigraphic dating of the early linguiformis Zone sequence boundary

Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson’s disease

Background: Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates. Methods: Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models. Results: The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models. Conclusion: The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use

Evaluation of a community health worker intervention and the World Health Organization’s Option B versus Option A to improve antenatal care and PMTCT outcomes in Dar es Salaam, Tanzania: study protocol for a cluster-randomized controlled health systems implementation trial

Background: Mother-to-child transmission of HIV remains an important public health problem in sub-Saharan Africa. As HIV testing and linkage to PMTCT occurs in antenatal care (ANC), major challenges for any PMTCT option in developing countries, including Tanzania, are delays in the first ANC visit and a low overall number of visits. Community health workers (CHWs) have been effective in various settings in increasing the uptake of clinical services and improving treatment retention and adherence. At the beginning of this trial in January 2013, the World Health Organization recommended either of two medication regimens, Option A or B, for prevention of mother-to-child transmission of HIV (PMTCT). It is still largely unclear which option is more effective when implemented in a public healthcare system. This study aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of: (1) a community health worker (CWH) intervention and (2) PMTCT Option B in improving ANC and PMTCT outcomes. Methods/Design This study is a cluster-randomized controlled health systems implementation trial with a two-by-two factorial design. All 60 administrative wards in the Kinondoni and Ilala districts in Dar es Salaam were first randomly allocated to either receiving the CHW intervention or not, and then to receiving either Option B or A. Under the standard of care, facility-based health workers follow up on patients who have missed scheduled appointments for PMTCT, first through a telephone call and then with a home visit. In the wards receiving the CHW intervention, the CHWs: (1) identify pregnant women through home visits and refer them to antenatal care; (2) provide education to pregnant women on antenatal care, PMTCT, birth, and postnatal care; (3) routinely follow up on all pregnant women to ascertain whether they have attended ANC; and (4) follow up on women who have missed ANC or PMTCT appointments. Trial registration ClinicalTrials.gov: EJF22802. Registration date: 14 May 2013. Electronic supplementary material The online version of this article (doi:10.1186/1745-6215-15-359) contains supplementary material, which is available to authorized users

The ART Advantage: Health Care Utilization for Diabetes and Hypertension in Rural South Africa

The prevalence of diabetes and hypertension has increased in HIV-positive populations, but there is limited understanding of the role that antiretroviral therapy (ART) programs play in the delivery of services for these conditions. The aim of this study is to assess the relationship between ART use and utilization of health care services for diabetes and hypertension.Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa is a cohort of 5059 adults. The baseline study collects biomarker-based data on HIV, ART, diabetes, and hypertension and self-reported data on health care utilization. We calculated differences in care utilization for diabetes and hypertension by HIV and ART status and used multivariable logistic regressions to estimate the relationship between ART use and utilization of services for these conditions, controlling for age, sex, body mass index, education, and household wealth quintile.Mean age, body mass index, hypertension, and diabetes prevalence were lower in the HIV-positive population (all P < 0.001). Multivariable logistic regression showed that ART use was significantly associated with greater odds of blood pressure measurement [adjusted odds ratio (aOR) 1.27, 95% confidence interval (CI): 1.04 to 1.55] and blood sugar measurement (aOR 1.26, 95% CI: 1.05 to 1.51), counseling regarding exercise (aOR 1.57, 95% CI: 1.11 to 2.22), awareness of hypertension diagnosis (aOR 1.52, 95% CI: 1.12 to 2.05), and treatment for hypertension (aOR 1.63, 95% CI: 1.21 to 2.19).HIV-positive patients who use ART are more likely to have received health care services for diabetes and hypertension. This apparent ART advantage suggests that ART programs may be a vehicle for strengthening health systems for chronic care

Community Health Workers to Improve Antenatal Care and PMTCT Uptake in Dar es Salaam, Tanzania: A Quantitative Performance Evaluation

Background: Home visits by community health workers (CHW) could be effective in identifying pregnant women in the community before they have presented to the health system. CHW could thus improve the uptake of antenatal care (ANC), HIV testing, and prevention of mother-to-child transmission (PMTCT) services. Methods: Over a 16-month period, we carried out a quantitative evaluation of the performance of CHW in reaching women early in pregnancy and before they have attended ANC in Dar es Salaam, Tanzania. Results: As part of the intervention, 213 CHW conducted more than 45,000 home visits to about 43,000 pregnant women. More than 75% of the pregnant women identified through home visits had not yet attended ANC at the time of the first contact with a CHW and about 40% of those who had not yet attended ANC were in the first trimester of pregnancy. Over time, the number of pregnant women the CHW identified each month increased, as did the proportion of women who had not yet attended ANC. The median gestational age of pregnant women contacted for the first time by a CHW decreased steadily and significantly over time (from 21/22 to 16 weeks, P-value for test of trend <0.0001). Conclusions: A large-scale CHW intervention was effective in identifying pregnant women in their homes early in pregnancy and before they had attended ANC. The intervention thus fulfills some of the conditions that are necessary for CHW to improve timely ANC uptake and early HIV testing and PMTCT enrollment in pregnancy