Incidence and admission rates for severe malaria and their impact on mortality in Africa

Appropriate treatment of life-threatening Plasmodium falciparum malaria requires in-patient care. Although the proportion of severe cases accessing in-patient care in endemic settings strongly affects overall case fatality rates and thus disease burden, this proportion is generally unknown. At present, estimates of malaria mortality are driven by prevalence or overall clinical incidence data, ignoring differences in case fatality resulting from variations in access. Consequently, the overall impact of preventive interventions on disease burden have not been validly compared with those of improvements in access to case management or its quality.; Using a simulation-based approach, severe malaria admission rates and the subsequent severe malaria disease and mortality rates for 41 malaria endemic countries of sub-Saharan Africa were estimated. Country differences in transmission and health care settings were captured by use of high spatial resolution data on demographics and falciparum malaria prevalence, as well as national level estimates of effective coverage of treatment for uncomplicated malaria. Reported and modelled estimates of cases, admissions and malaria deaths from the World Malaria Report, along with predicted burden from simulations, were combined to provide revised estimates of access to in-patient care and case fatality rates.; There is substantial variation between countries' in-patient admission rates and estimated levels of case fatality rates. It was found that for many African countries, most patients admitted for in-patient treatment would not meet strict criteria for severe disease and that for some countries only a small proportion of the total severe cases are admitted. Estimates are highly sensitive to the assumed community case fatality rates. Re-estimation of national level malaria mortality rates suggests that there is substantial burden attributable to inefficient in-patient access and treatment of severe disease.; The model-based methods proposed here offer a standardized approach to estimate the numbers of severe malaria cases and deaths based on national level reporting, allowing for coverage of both curative and preventive interventions. This makes possible direct comparisons of the potential benefits of scaling-up either category of interventions. The profound uncertainties around these estimates highlight the need for better data

Kinematic classifications of local interacting galaxies: implications for the merger/disk classifications at high-z

The classification of galaxy mergers and isolated disks is key for understanding the relative importance of galaxy interactions and secular evolution during the assembly of galaxies. The kinematic properties of galaxies as traced by emission lines have been used to suggest the existence of a significant population of high-z star-forming galaxies consistent with isolated rotating disks. However, recent studies have cautioned that post-coalescence mergers may also display disk-like kinematics. To further investigate the robustness of merger/disk classifications based on kinematic properties, we carry out a systematic classification of 24 local (U)LIRGs spanning a range of galaxy morphologies: from isolated spiral galaxies, ongoing interacting systems, to fully merged remnants. We artificially redshift the WiFeS observations of these local (U)LIRGs to z=1.5 to make a realistic comparison with observations at high-z, and also to ensure that all galaxies have the same spatial sampling of ~900 pc. Using both kinemetry-based and visual classifications, we find that the reliability of kinematic classification shows a strong trend with the interaction stage of galaxies. Mergers with two nuclei and tidal tails have the most distinct kinematic properties compared to isolated disks, whereas a significant population of the interacting disks and merger remnants are indistinguishable from isolated disks. The high fraction of late-stage mergers showing disk-like kinematics reflects the complexity of the dynamics during galaxy interactions. However, the exact fractions of misidentified disks and mergers depend on the definition of kinematic asymmetries and the classification threshold when using kinemetry-based classifications. Our results suggest that additional indicators such as morphologies traced by stars or molecular gas are required to further constrain the merger/disk classifications at high-z.Comment: 16 pages, 5 figures, ApJ accepte

Carbon and Oxygen Abundances in the Hot Jupiter Exoplanet Host Star XO-2N and its Binary Companion

With the aim of connecting the compositions of stars and planets, we present the abundances of carbon and oxygen, as well as iron and nickel, for the transiting exoplanet host star XO-2N and its wide-separation binary companion XO-2S. Stellar parameters are derived from high-resolution, high-signal-to-noise spectra, and the two stars are found to be similar in their Teff, log g, iron ([Fe/H]), nickel ([Ni/H]) abundances. Their carbon ([C/H]) and oxygen ([O/H]) abundances also overlap within errors, although XO-2N may be slightly more C-rich and O-rich than XO-2S. The C/O ratios of both stars (~0.60+/-0.20) may also be somewhat larger than solar (C/O~0.50). The XO-2 system has a transiting hot Jupiter orbiting one binary component but not the other, allowing us to probe the potential effects planet formation might have on the host star composition. Additionally, with multiple observations of its atmosphere the transiting exoplanet XO-2b lends itself to compositional analysis, which can be compared to the natal chemical environment established by our binary star elemental abundances. This work sets the stage for determining how similar/different exoplanet and host star compositions are, and the implications for planet formation, by discussing the C/O ratio measurements in the unique environment of a visual binary system with one star hosting a transiting hot Jupiter.Comment: 19 pages, 2 figures, 2 tables; accepted for publication in Astrophysical Journal Letter

Soil Microbial Networks Shift Across a High-Elevation Successional Gradient.

While it is well established that microbial composition and diversity shift along environmental gradients, how interactions among microbes change is poorly understood. Here, we tested how community structure and species interactions among diverse groups of soil microbes (bacteria, fungi, non-fungal eukaryotes) change across a fundamental ecological gradient, succession. Our study system is a high-elevation alpine ecosystem that exhibits variability in successional stage due to topography and harsh environmental conditions. We used hierarchical Bayesian joint distribution modeling to remove the influence of environmental covariates on species distributions and generated interaction networks using the residual species-to-species variance-covariance matrix. We hypothesized that as ecological succession proceeds, diversity will increase, species composition will change, and soil microbial networks will become more complex. As expected, we found that diversity of most taxonomic groups increased over succession, and species composition changed considerably. Interestingly, and contrary to our hypothesis, interaction networks became less complex over succession (fewer interactions per taxon). Interactions between photosynthetic microbes and any other organism became less frequent over the gradient, whereas interactions between plants or soil microfauna and any other organism were more abundant in late succession. Results demonstrate that patterns in diversity and composition do not necessarily relate to patterns in network complexity and suggest that network analyses provide new insight into the ecology of highly diverse, microscopic communities

Pressor and Sympathetic Responses to Graded Skeletal Muscle Metaboreflex Activation in Females with Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a progressive disease characterized by demyelination in the central nervous system which disproportionately impacts females. Previous studies suggest MS-related exercise intolerance may be due to abnormal control of arterial blood pressure (BP) via the skeletal muscle metaboreflex. However, few studies have been performed and equivocal results reported. Discontinuity in prior data may be due to limited perturbation of metaboreflex activation using only low and moderate intensity exercise. PURPOSE: The purpose of this investigation was to test the hypothesis that females with MS have blunted BP and sympathetic responses to graded static handgrip (HG) exercise and isolated metaboreflex activation during postexercise ischemia (PEI) compared to healthy controls. METHODS: In 7 females with relapsing-remitting MS and 9 healthy female controls beat-to-beat BP (finometer) and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were recorded at rest and during two minutes of handgrip performed at 30% and 40% maximum voluntary contraction followed by two minutes of PEI to isolate the muscle metaboreflex. RESULTS: There were no differences in resting mean arterial pressure (MAP; P= 0.16) or MSNA burst frequency (P= 0.15) between MS and controls. MAP and MSNA increased during 30% HG (MS: Δ19.8 ± 9.1 mmHg vs. Con: Δ17.8 ± 5.4 mmHg; P= 0.30 and MS: Δ17 ± 12 bursts/min vs. Con: Δ18 ± 17 bursts/min; P= 0.46) and 40% HG (MS: Δ29.3 ± 8.0 mmHg vs. Con: Δ30.0 ± 6.9 mmHg; P= 0.43 and MS: Δ36 ± 16 bursts/min vs. Con: Δ40 ± 9 bursts/min; P= 0.30) with no differences between groups. Likewise, MAP and MSNA responses were also not different during PEI post 30% HG (MS: Δ15.8 ± 7.6 mmHg vs. Con: Δ15.8 ± 6.4 mmHg; P= 0.50 and MS: Δ15 ± 9 bursts/min vs. Con: Δ11 ± 7 bursts/min; P= 0.19) or PEI post 40% HG (MS: Δ25.8 ± 6.3 mmHg vs. Con: Δ22.6 ± 8.2 mmHg; P= 0.43 and MS: Δ23 ± 13 bursts/min vs. Con: Δ24 ± 7 bursts/min; P= 0.46) between MS and controls. CONCLUSION: These preliminary data suggest intact skeletal muscle metaboreflex control of arterial BP in females with MS

Patient Perspectives and Experiences of Preventive Treatments and Self-Injectable Devices for Migraine:A Focus Group Study

BACKGROUND: Although several self-injectable preventive treatments for migraine have become available, they are not yet widely used. Thus, understanding patients’ perceptions towards them is limited. OBJECTIVE: This study aimed to inform the design of a preference-elicitation instrument, which is being developed to quantify preventive treatment preferences of people with migraine. METHODS: We conducted a qualitative study involving nine in-person focus groups (three per country) in the United States, the United Kingdom, and Germany. Participants were adults (n = 47) with episodic or chronic migraine who were currently using or had used a prescription preventive treatment for migraine within the previous 5 years. During the focus groups, participants described their experiences of migraine and preventive treatments; handled and simulated self-injection using five different unbranded, fired demonstration auto-injectors and prefilled syringes; and ranked different aspects of preventive treatments by importance. Focus groups were analyzed with a focus on themes that would be feasible or meaningful to include in a subsequent preference-elicitation instrument. RESULTS: Reducing the frequency and severity of migraine attacks was consistently ranked as the most important aspect of preventive treatment. Participants expressed dissatisfaction with available daily oral preventive treatments for migraine they had previously used because they were ineffective or caused intolerable adverse events. Many participants were willing to self-inject a treatment that was effective and tolerable. When presented with devices for self-injecting a preventive treatment for migraine, participants generally preferred autoinjectors over prefilled syringes. Participants especially valued safety features such as the unlocking step and automated needle insertion, and audible and visual dose confirmation increased confidence in autoinjector use. Autoinjector needle protection mechanisms were also appreciated, especially by participants averse to needles, as the needles are not visible. CONCLUSIONS: This study highlights the fact that many people with migraine still lack access to a preventive treatment that is effective and tolerable. In addition to efficacy and safety considerations, treatment decisions may be guided by the mode of administration. In the case of self-injectable preventive treatments, key device characteristics affecting these decisions may be ease of use, comfort, and confidence in self-injection. Insights gained from this study were used to help develop a preliminary set of attributes and levels for a preference-elicitation instrument. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40271-021-00525-z