Deriving phytoplankton size classes from satellite data: Validation along a trophic gradient in the eastern Atlantic Ocean

In recent years, the global distribution of phytoplankton functional types (PFT) and phytoplankton size classes (PSC) has been determined by remote sensing. Many of these methods rely on interpretation of phytoplankton size or type from pigment data, but independent validation has been difficult due to lack of appropriate in situ data on cell size. This work uses in situ data (photosynthetic pigments concentration and cell abundances) from the north-east Atlantic, along a trophic gradient, sampled from 2005 to 2010, as well as Atlantic Meridional Transect (AMT) data for the same region, to test a previously developed conceptual model, which calculates the fractional contributions of pico-, nano- and micro-plankton to total phytoplankton chlorophyll biomass (Brewin et al., 2010). The application of the model proved to be successful, as shown by low mean absolute error between data and model fit. However, regional values obtained for the model parameters had some effect on the relative distribution of size classes as a function of chlorophyll-a, compared with the results according to the original model. The regional parameterisation yielded a dominance of micro-plankton contribution for chlorophyll-a concentrations greater than 0.5 mg m− 3, rather than from 1.3 mg m− 3 in the original model. Intracellular chlorophyll-a (Chla) per cell, for each size class, was computed from the cell enumeration results (microscope counts and flow cytometry) and the chlorophyll-a concentration for that size class given by the model. The median intracellular chlorophyll-a values computed were 0.004, 0.224 and 26.78 pg Chla cell− 1 for pico-, nano-, and micro-plankton respectively. This is generally consistent with the literature, thereby providing an indirect validation of the method based on pigments to assign size classes. Using a satellite-derived composite image of chlorophyll-a for the study area, a map of cell abundance was generated based on the computed intracellular chlorophyll-a for each size-class, thus extending the remote-sensing method for mapping size classes of phytoplankton from chlorophyll-a concentration to mapping cell numbers in each class. The map reveals the ubiquitous presence of pico-plankton, and shows that all size classes are more abundant in more productive areas

We know DAAs work, so now what?:Simplifying models of care to enhance the hepatitis C cascade

Globally, some 71 million people are chronically infected with hepatitis C virus (HCV). Marginalised populations, particularly people who inject drugs (PWID), have low testing, linkage-to-care and treatment rates for HCV. Several models of care (MoCs) and service delivery interventions have the potential to improve outcomes across the HCV cascade of care, but much of the relevant research was carried out when interferon-based treatment was the standard of care. Often it was not practical to scale up these earlier models and interventions because the clinical care needs of patients taking interferon-based regimens imposed too much of a financial and human resource burden on health systems. Despite the adoption of highly effective, all-oral direct-acting antiviral (DAA) therapies in recent years, approaches to HCV testing and treatment have evolved slowly and often remain rooted in earlier paradigms. The effectiveness of DAAs allows for simpler approaches and has encouraged countries where the drugs are widely available to set their sights on the ambitious World Health Organization (WHO) HCV elimination targets. Since a large proportion of chronically HCV-infected people are not currently accessing treatment, there is an urgent need to identify and implement existing simplified MoCs that speak to specific populations' needs. This article aims to: 1) review the evidence on MoCs for HCV; and 2) distil the findings into recommendations for how stakeholders can simplify the path taken by chronically HCV-infected individuals from testing to cure and subsequent care and monitoring

Early Steps of HIV-1 Fusion Define the Sensitivity to Inhibitory Peptides That Block 6-Helix Bundle Formation

The HIV envelope (Env) glycoprotein mediates membrane fusion through sequential interactions with CD4 and coreceptors, followed by the refolding of the transmembrane gp41 subunit into the stable 6-helix bundle (6HB) conformation. Synthetic peptides derived from the gp41 C-terminal heptad repeat domain (C-peptides) potently inhibit fusion by binding to the gp41 pre-bundle intermediates and blocking their conversion into the 6HB. Our recent work revealed that HIV-1 enters cells by fusing with endosomes, but not with the plasma membrane. These studies also showed that, for the large part, gp41 pre-bundles progress toward 6HBs in endosomal compartments and are thus protected from external fusion inhibitors. Here, we examined the consequences of endocytic entry on the gp41 pre-bundle exposure and on the virus' sensitivity to C-peptides. The rates of CD4 and coreceptor binding, as well as the rate of productive receptor-mediated endocytosis, were measured by adding specific inhibitors of these steps at varied times of virus-cell incubation. Following the CD4 binding, CCR5-tropic viruses recruited a requisite number of coreceptors much faster than CXCR4-tropic viruses. The rate of subsequent uptake of ternary Env-CD4-coreceptor complexes did not correlate with the kinetics of coreceptor engagement. These measurements combined with kinetic analyses enabled the determination of the lifetime of pre-bundle intermediates on the cell surface. Overall, these lifetimes correlated with the inhibitory potency of C-peptides. On the other hand, the basal sensitivity to peptides varied considerably among diverse HIV-1 isolates and ranked similarly with their susceptibility to inactivation by soluble CD4. We conclude that both the longevity of gp41 intermediates and the extent of irreversible conformational changes in Env upon CD4 binding determine the antiviral potency of C-peptides

Incidence of stillbirth and perinatal mortality and their associated factors among women delivering at Harare Maternity Hospital, Zimbabwe: a cross-sectional retrospective analysis

BACKGROUND: Death of an infant in utero or at birth has always been a devastating experience for the mother and of concern in clinical practice. Infant mortality remains a challenge in the care of pregnant women worldwide, but particularly for developing countries and the need to understand contributory factors is crucial for addressing appropriate perinatal health. METHODS: Using information available in obstetric records for all deliveries (17,072 births) at Harare Maternity Hospital, Zimbabwe, we conducted a cross-sectional retrospective analysis of a one-year data, (1997–1998) to assess demographic and obstetric risk factors for stillbirth and early neonatal death. We estimated risk of stillbirth and early neonatal death for each potential risk factor. RESULTS: The annual frequency of stillbirth was 56 per 1,000 total births. Women delivering stillbirths and early neonatal deaths were less likely to receive prenatal care (adjusted relative risk [RR] = 2.54; 95% confidence intervals [CI] 2.19–2.94 and RR = 2.52; 95% CI 1.63–3.91), which for combined stillbirths and early neonatal deaths increased with increasing gestational age (Hazard Ratio [HR] = 3.98, HR = 7.49 at 28 and 40 weeks of gestation, respectively). Rural residence was associated with risk of infant dying in utero, (RR = 1.33; 95% CI 1.12–1.59), and the risk of death increased with increasing gestational age (HR = 1.04, HR = 1.69, at 28 and 40 weeks of gestation, respectively). Older maternal age was associated with risk of death (HR = 1.50; 95% CI 1.21–1.84). Stillbirths were less likely to be delivered by Cesarean section (RR = 0.64; 95% CI 0.51–0.79), but more likely to be delivered as breech (RR = 4.65; 95% CI 3.88–5.57, as were early neonatal deaths (RR = 3.38; 95% CI 1.64–6.96). CONCLUSION: The frequency of stillbirth, especially macerated, is high, 27 per 1000 total births. Early prenatal care could help reduce perinatal death linking the woman to the health care system, increasing the probability that she would seek timely emergency care that would reduce the likelihood of death of her infant in utero. Improved quality of obstetric care during labor and delivery may help reduce the number of fresh stillbirths and early neonatal deaths

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Social and Structural Factors Associated with HIV Infection among Female Sex Workers Who Inject Drugs in the Mexico-US Border Region

BACKGROUND: FSWs who inject drugs (FSW-IDUs) can acquire HIV through high risk sexual and injection behaviors. We studied correlates of HIV infection among FSW-IDUs in northern Mexico, where sex work is quasi-legal and syringes can be legally obtained without a prescription. METHODS: FSW-IDUs>18 years old who reported injecting drugs and recent unprotected sex with clients in Tijuana and Ciudad Juarez underwent surveys and HIV/STI testing. Logistic regression identified correlates of HIV infection. RESULTS: Of 620 FSW-IDUs, prevalence of HIV, gonorrhea, Chlamydia, trichomonas, syphilis titers ≥1:8, or any of these infections was 5.3%, 4%, 13%, 35%, 10% and 72%, respectively. Compared to other FSW-IDUs, HIV-positive women were more likely to: have syphilis titers ≥1:8 (36% vs. 9%, p<0.001), often/always inject drugs with clients (55% vs. 32%, p = 0.01), and experience confiscation of syringes by police (49% vs. 28%, p = 0.02). Factors independently associated with HIV infection were syphilis titers ≥1:8, often/always injecting with clients and police confiscation of syringes. Women who obtained syringes from NEPs (needle exchange programs) within the last month had lower odds of HIV infection associated with active syphilis, but among non-NEP attenders, the odds of HIV infection associated with active syphilis was significantly elevated. CONCLUSIONS: Factors operating in both the micro-social environment (i.e., injecting drugs with clients) and policy environment (i.e., having syringes confiscated by police, attending NEPs) predominated as factors associated with risk of HIV infection, rather than individual-level risk behaviors. Interventions should target unjustified policing practices, clients' risk behaviors and HIV/STI prevention through NEPs

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders