Restricted Full Three-Body Problem: Application to Binary System 1999 KW4

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76569/1/AIAA-30937-245.pd

Healthcare-seeking Behaviour for Common Infectious Disease-related Illnesses in Rural Kenya: A Community-based House-to-house Survey

Community surveys of healthcare-use determine the proportion of illness episodes not captured by health facility-based surveillance, the methodology used most commonly to estimate the burden of disease in Africa. A cross-sectional survey of households with children aged less than five years was conducted in 35 of 686 census enumeration areas in rural Bondo district, western Kenya. Healthcare sought for acute episodes of diarrhoea or fever in the past two weeks or pneumonia in the past year was evaluated. Factors associa-ted with healthcare-seeking were analyzed by logistic regression accounting for sample design. In total, 6,223 residents of 981 households were interviewed. Of 1,679 children aged less than five years, 233 (14%) had diarrhoea, and 736 (44%) had fever during the past two weeks; care at health facilities was sought for one-third of these episodes. Pneumonia in the past year was reported for 64 (4%) children aged less than five years; 88% sought healthcare at any health facility and 48% at hospitals. Seeking healthcare at health facilities was more likely for children from households with higher socioeconomic status and with more symptoms of severe illness. Health facility and hospital-based surveillance would underestimate the burden of disease substantially in rural western Kenya. Seeking healthcare at health facilities and hospitals varied by syndrome, severity of illness, and characteristics of the patient

Putting surveillance data into context: The role of health care utilization surveys in understanding population burden of pneumonia in developing countries

AbstractBackgroundSurveillance is essential to estimating the global burden of pneumonia, yet differences in surveillance methodology and health care-seeking behaviors limit inter-country comparisons.MethodsResults were compared from community surveys measuring health care-seeking for pneumonia defined as: (1) cough and difficulty breathing for ⩾2days; or, (2) provider-diagnosed pneumonia. Surveys were conducted in six sites in Guatemala, Kenya and Thailand; these sites also conduct, active, hospital- and population-based disease surveillance for pneumonia.ResultsFrequency of self-reported pneumonia during the preceding year ranged from 1.1% (Thailand) to 6.3% (Guatemala) and was highest in children aged <5years and in urban sites. The proportion of persons with pneumonia who sought hospital-based medical services ranged from 12% (Guatemala, Kenya) to 80% (Thailand) and was highest in children <5years of age. Hospitals and private provider offices were the most common places where persons with pneumonia sought health care. The most commonly cited reasons for not seeking health care were: (a) mild illness; (b) already recovering; and (3) cost of treatment.ConclusionsHealth care-seeking patterns varied widely across countries. Using results from standardized health care utilization surveys to adjust facility-based surveillance estimates of pneumonia allows for more accurate and comparable estimates

Healthcare-seeking Behaviour for Common Infectious Disease-related Illnesses in Rural Kenya: A Community-based House-to-house Survey

Community surveys of healthcare-use determine the proportion of illness episodes not captured by health facility-based surveillance, the methodology used most commonly to estimate the burden of disease in Africa. A cross-sectional survey of households with children aged less than five years was conducted in 35 of 686 census enumeration areas in rural Bondo district, western Kenya. Healthcare sought for acute episodes of diarrhoea or fever in the past two weeks or pneumonia in the past year was evaluated. Factors associated with healthcare-seeking were analyzed by logistic regression accounting for sample design. In total, 6,223 residents of 981 households were interviewed. Of 1,679 children aged less than five years, 233 (14%) had diarrhoea, and 736 (44%) had fever during the past two weeks; care at health facilities was sought for one-third of these episodes. Pneumonia in the past year was reported for 64 (4%) children aged less than five years; 88% sought healthcare at any health facility and 48% at hospitals. Seeking healthcare at health facilities was more likely for children from households with higher socioeconomic status and with more symptoms of severe illness. Health facility and hospital-based surveillance would underestimate the burden of disease substantially in rural western Kenya. Seeking healthcare at health facilities and hospitals varied by syndrome, severity of illness, and characteristics of the patient

Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study).

OBJECTIVES: Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making. DESIGN: A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020. SETTING: Regional neurosurgical units outside London (as the pandemic was more advanced at time of study). PARTICIPANTS: Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK. RESULTS: 18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed-the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%-28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected. CONCLUSION: COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments-most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures. STUDY REGISTRATION: This study was registered with the Royal College of Surgeons of England's COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/)

Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations

Objective: To investigate mitophagy in 5 patients with severe dominantly inherited optic atrophy (DOA), caused by depletion of OPA1 (a protein that is essential for mitochondrial fusion), compared with healthy controls. Methods: Patients with severe DOA (DOA plus) had peripheral neuropathy, cognitive regression, and epilepsy in addition to loss of vision. We quantified mitophagy in dermal fibroblasts, using 2 high throughput imaging systems, by visualizing colocalization of mitochondrial fragments with engulfing autophagosomes. Results: Fibroblasts from 3 biallelic OPA1(2/2) patients with severe DOA had increased mitochondrial fragmentation and mitochondrial DNA (mtDNA)–depleted cells due to decreased levels of OPA1 protein. Similarly, in siRNA-treated control fibroblasts, profound OPA1 knockdown caused mitochondrial fragmentation, loss of mtDNA, impaired mitochondrial function, and mitochondrial mislocalization. Compared to controls, basal mitophagy (abundance of autophagosomes colocalizing with mitochondria) was increased in (1) biallelic patients, (2) monoallelic patients with DOA plus, and (3) OPA1 siRNA–treated control cultures. Mitophagic flux was also increased. Genetic knockdown of the mitophagy protein ATG7 confirmed this by eliminating differences between patient and control fibroblasts. Conclusions: We demonstrated increased mitophagy and excessive mitochondrial fragmentation in primary human cultures associated with DOA plus due to biallelic OPA1 mutations. We previously found that increased mitophagy (mitochondrial recycling) was associated with visual loss in another mitochondrial optic neuropathy, Leber hereditary optic neuropathy (LHON). Combined with our LHON findings, this implicates excessive mitochondrial fragmentation, dysregulated mitophagy, and impaired response to energetic stress in the pathogenesis of mitochondrial optic neuropathies, potentially linked with mitochondrial mislocalization and mtDNA depletion

Sedimentology, chemostratigraphy, and stromatolites of lower Paleoproterozoic carbonates, Turee Creek Group, Western Australia

The ca. 2.45–2.22 Ga Turee Creek Group, Western Australia, contains carbonate- rich horizons that postdate earliest Proterozoic iron formations, bracket both Paleoproterozoic glaciogenic beds and the onset of the Great Oxidation Event (GOE), and predate ca. 2.2–2.05 Ga Lomagundi-Jatuli C-isotopic excursion(s). As such, Turee Creek carbonate strata provide an opportunity to characterize early Paleoproterozoic carbonate sedimentation and carbon cycle dynamics in the context of significant global change. Here, we report on the stratigraphy, sedimentology, petrology, carbon isotope chemostratigraphy, and stromatolite development for carbonate-rich successions within the pre-glacial part of the Kungarra Formation and the postglacial Kazput Formation. Kungarra carbonate units largely occur as laterally discontinuous beds within a thick, predominantly siliciclastic shelf deposit. While this succession contains thin microbialite horizons, most carbonates consist of patchy calcite overgrowths within a siliciclastic matrix. C-isotopic values show marked variation along a single horizon and even within hand samples, reflecting spatially and temporally variable mixing between dissolved inorganic carbon in seawater and isotopically light inorganic carbon generated via syn- and post-depositional remineralization of organic matter. In contrast, the Kazput carbonates consist of subtidal stromatolites, grainstones, and micrites deposited on a mixed carbonate-siliciclastic shelf. These carbonates exhibit moderate δ13 C values of -2‰ to +1.5‰ and likely preserve a C-isotopic signature of seawater. Kazput carbonates, thus, provide some of the best available evidence that an interval of unexceptional C-isotopic values separates the Lomagundi-Jatuli C-isotopic excursion(s) from the initiation of the GOE as inferred from multiple sulfur isotopes (loss 4 of mass independent fractionation). The Kazput Formation also contains unusual, m-scale stromatolitic buildups, which are composed of sub-mm laminae and discontinuous, convex upward lenticular precipitates up to a few mm in maximum thickness. Laminae, interpreted as microbial mat layers, contain quartz and clay minerals as well as calcite, whereas precipitate lenses consist of interlocking calcite anhedra, sometimes showing faint mm-scale banding. These cements formed either as infillings of primary voids formed by gas emission within penecontemporaneously lithified mats, or as local seafloor precipitates that formed on, or within, surface mats. It is possible that both mechanisms interacted to form the unique Kazput stromatolites. These microbialites speak to a distinctive interaction between life and environment early in the Paleoproterozoic Era.Earth and Planetary Science

Multimodal characterization of the late effects of traumatic brain injury: a methodological overview of the Late Effects of Traumatic Brain Injury Project

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer’s and Parkinson’s disease (AD and PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional MRI, and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study