Pharmacologic management of Mycobacterium ulcerans infection

Introduction: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. Areas covered: We review BU drug treatment–in vitro, in vivo and clinical trials (PubMed: ‘(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).’ We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. Expert opinion: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer

Developing Priorities for the Great Northern Landscape Conservation Cooperative: State Wildlife Action Plans (SWAP) as One Piece of Information

Landscape Conservation Cooperatives (LCCs) are public-private partnerships that focus on natural resource challenges which transcend political and jurisdictional boundaries and require a more holistic, collaborative, and adaptive approach to conservation that is firmly grounded in science and strives to ensure the sustainability of land, water, wildlife and cultural resources. The Great Northern LCC, covering Western Montana and parts of several other states and provinces, is nearing completion of a process that synthesizes conservation priorities among the 25 organizations represented on the Steering Committee and their partners. This Strategic Conservation Framework identifies priority species, ecosystems, and ecosystem processes across the landscape represented by the Great Northern LCC based on synthetic summarizations of five state-based Wildlife Action Plans, 40 other regional conservation planning documents, and focused interviews with key personnel across the region. Here we report on the process by which we analyzed data from the State Wildlife Action Plans (SWAPs) of ID, MT, OR, WA, and WY and from Strategic Habitat Conservation as one piece of information for strategic planning. Thirty-five species of greatest conservation need (as defined in the SWAPs) were identified as having commonality across the five states. The ranges of these species were then overlain and a map of areas with the greatest number of species of conservation need can be visualized across the Great Northern LCC

Using the minimum spanning tree to trace mass segregation

We present a new method to detect and quantify mass segregation in star clusters. It compares the minimum spanning tree (MST) of massive stars with that of random stars. If mass segregation is present, the MST length of the most massive stars will be shorter than that of random stars. This difference can be quantified (with an associated significance) to measure the degree of mass segregation. We test the method on simulated clusters in both 2D and 3D and show that the method works as expected. We apply the method to the Orion Nebula Cluster (ONC) and show that the method is able to detect the mass segregation in the Trapezium with a `mass segregation ratio' \Lambda_{MSR}=8.0 \pm 3.5 (where \Lambda_{MSR}=1 is no mass segregation) down to 16 \Msun, and also that the ONC is mass segregated at a lower level (~2.0 \pm 0.5) down to 5 \Msun. Below 5 \Msun we find no evidence for any further mass segregation in the ONC.Comment: Accepted in MNRA

Correlation between Quantitative PCR and Culture-Based Methods for Measuring Enterococcus spp. over Various Temporal Scales at Three California Marine Beaches

ABSTRACT Several studies have examined how fecal indicator bacteria (FIB) measurements compare between quantitative PCR (qPCR) and the culture methods it is intended to replace. Here, we extend those studies by examining the stability of that relationship within a beach, as affected by time of day and seasonal variations in source. Enterococcus spp. were quantified at three southern California beaches in the morning and afternoon using two qPCR assays, membrane filtration, and defined-substrate testing. While qPCR and culture-based measurements were consistently and significantly correlated, strength of the correlation varied both among and within beaches. Correlations were higher in the morning (0.45 < ρ < 0.74 [ P < 0.002]) than in the afternoon (0.18 < ρ < 0.45 [ P < 0.021]) and higher when the fecal contamination was concentrated (0.38 < ρ < 0.83 [ P < 0.001]) than when it was diffuse (0.19 < ρ < 0.34 [ P < 0.003]). The ratios of culture-based and qPCR results (CFU or most probable number [MPN] per calibrator cell equivalents [CCE]) also varied spatially and temporally. Ratios ranged between 0.04 and 0.85 CFU or MPN per CCE and were lowest at the beach affected by diffuse pollution. Patterns in the ratios over the course of the day were dissimilar across beaches, increasing with time at one beach and decreasing at another. The spatial and temporal variability we observed indicate that the empirical relationship between culture-based and qPCR results is not universal, even within a beach

Defining Anuran Malformations in the Context of a Developmental Problem

This paper summarizes terminology and general concepts involved in animal development for the purpose of providing background for the study and understanding of frog malformations. The results of our radiographic investigation of rear limb malformations in Rana pipiens provide evidence that frog malformations are the product of early developmental errors. Although bacteria, parasites and viruses were identified in these metamorphosed frogs, the relevant window to look for the teratogenic affect of these agents is in the early tadpole stage during limb development. As a result, our microbiological findings must be regarded as inconclusive relative to determining their contribution to malformations because we conducted our examinations on metamorphosed frogs not tadpoles. Future studies need to look at teratogenic agents (chemical, microbial, physical or mechanical) that are present in the embryo, tadpole, and their environments at stages of development that are relevant for the malformation type. The impact of these teratogenic agents then needs to be assessed in appropriate animal models using studies that are designed to mimic field conditions. The results of these laboratory tests should then be analyzed in such a way that will allow comparison with the findings in the wild-caught tadpoles and frogs

Development of online use of theory of mind during adolescence: an eye-tracking study

We investigated the development of theory of mind use through eye-tracking in children (9–13 years old, n = 14), adolescents (14–17.9 years old, n = 28), and adults (19–29 years old, n = 23). Participants performed a computerized task in which a director instructed them to move objects placed on a set of shelves. Some of the objects were blocked off from the director’s point of view; therefore, participants needed to take into consideration the director’s ignorance of these objects when following the director’s instructions. In a control condition, participants performed the same task in the absence of the director and were told that the instructions would refer only to items in slots without a back panel, controlling for general cognitive demands of the task. Participants also performed two inhibitory control tasks. We replicated previous findings, namely that in the director-present condition, but not in the control condition, children and adolescents made more errors than adults, suggesting that theory of mind use improves between adolescence and adulthood. Inhibitory control partly accounted for errors on the director task, indicating that it is a factor of developmental change in perspective taking. Eye-tracking data revealed early eye gaze differences between trials where the director’s perspective was taken into account and those where it was not. Once differences in accuracy rates were considered, all age groups engaged in the same kind of online processing during perspective taking but differed in how often they engaged in perspective taking. When perspective is correctly taken, all age groups’ gaze data point to an early influence of perspective information

Reintroduction or natural colonisation? Using cost-distance analysis to inform decisions about Rodrigues Island Fody and Warbler reintroductions

When making decisions about reintroducing a species, practitioners need to consider whether the release site contains habitat suitable for those species, whether past extinction drivers have been remedied and whether reintroduction is the best option for the species to recolonise the release site. These concerns are captured within two paradigms; the habitat and metapopulation paradigms. We use cost-distance analysis to assess the need for reintroduction of two bird species, Rodrigues Fody and Rodrigues Warbler, to Anse Quitor reserve on Rodrigues Island, testing hypotheses based on these underlying paradigms. Given a lack of detailed field studies of dispersal across the landscape on either species we rely on expert judgement. Our results show that experts believe Rodrigues Fody will naturally colonise Anse Quitor but that Rodrigues Warbler may not, at least within a time frame of 10 years. This information and treatment of expert judgement allows greater justification in reintroduction planning. Our method shows one way to assist in reintroduction decision making in poorly studied systems

Importance of the Initial Conditions for Star Formation - III: Statistical Properties of Embedded Protostellar Clusters

We investigate the formation of protostellar clusters during the collapse of dense molecular cloud cores with a focus on the evolution of potential and kinetic energy, the degree of substructure, and the early phase of mass segregation. Our study is based on a series of hydrodynamic simulations of dense cores, where we vary the initial density profile and the initial turbulent velocity. In the three-dimensional adaptive mesh refinement simulations, we follow the dynamical formation of filaments and protostars until a star formation efficiency of 20%. Despite the different initial configurations, the global ensemble of all protostars in a setup shows a similar energy evolution and forms sub-virial clusters with an energy ratio $E_\mathrm{kin}/|E_\mathrm{pot}|\sim0.2$. Concentrating on the innermost central region, the clusters show a roughly virialised energy balance. However, the region of virial balance only covers the innermost $\sim10-30$ of all the protostars. In all simulations with multiple protostars, the total kinetic energy of the protostars is higher than the kinetic energy of the gas cloud, although the protostars only contain 20% of the total mass. The clusters vary significantly in size, mass, and number of protostars, and show different degrees of substructure and mass segregation. Flat density profiles and compressive turbulent modes produce more subclusters then centrally concentrated profiles and solenoidal turbulence. We find that dynamical relaxation and hence dynamical mass segregation is very efficient in all cases from the very beginning of the nascent cluster, i.e., during a phase when protostars are constantly forming and accreting.Comment: 19 pages, MNRAS accepte

Rapidly measured indicators of recreational water quality and swimming-associated illness at marine beaches: a prospective cohort study

<p>Abstract</p> <p>Introduction</p> <p>In the United States and elsewhere, recreational water quality is monitored for fecal indicator bacteria to help prevent swimming-associated illnesses. Standard methods to measure these bacteria take at least 24 hours to obtain results. Molecular approaches such as quantitative polymerase chain reaction (qPCR) can estimate these bacteria faster, in under 3 hours. Previously, we demonstrated that measurements of the fecal indicator bacteria <it>Enterococcus </it>using qPCR were associated with gastrointestinal (GI) illness among swimmers at freshwater beaches. In this paper, we report on results from three marine beach sites.</p> <p>Methods</p> <p>We interviewed beach-goers and collected water samples at marine beaches affected by treated sewage discharges in Mississippi in 2005, and Rhode Island and Alabama in 2007. Ten to twelve days later, we obtained information about gastrointestinal, respiratory, eye, ear and skin symptoms by telephone. We tested water samples for fecal indicator organisms using qPCR and other methods.</p> <p>Results</p> <p>We enrolled 6,350 beach-goers. The occurrence of GI illness among swimmers was associated with a log₁₀-increase in exposure to qPCR-determined estimates of fecal indicator organisms in the genus <it>Enterococcus </it>(AOR = 2.6, 95% CI 1.3-5.1) and order <it>Bacteroidales </it>(AOR = 1.9, 95% CI 1.3-2.9). Estimates of organisms related to <it>Clostridium perfringens </it>and a subgroup of organisms in the genus <it>Bacteroides </it>were also determined by qPCR in 2007, as was F+ coliphage, but relationships between these indicators and illness were not statistically significant.</p> <p>Conclusions</p> <p>This study provides the first evidence of a relationship between gastrointestinal illness and estimates of fecal indicator organisms determined by qPCR at marine beaches.</p