An application of linear covariance analysis to the design of responsive near-rendezvous missions

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2007.Cataloged from PDF version of thesis.Includes bibliographical references (p. 97).This thesis investigates a new class of launch vehicles capable of being released from an aircraft which ultimately have the goal of achieving near-rendezvous conditions at orbital altitudes up to 800 km. These launch vehicles would be capable of carrying small payloads, on the order of two to six kilograms, and would be much more responsive to a customer's needs than the current space launch infrastructure, in which it may take months of preparation for a launch. To fully describe the mission in this thesis, it is broken up into three phases: atmospheric launch, orbit raising, and near-rendezvous operations. An analysis method known as Linear Covariance analysis is introduced to provide a platform of estimating the navigation covariance and dispersion of the spacecraft during the second and third phases, while the first phase, up to main-engine-cutoff, is examined using a three degree-of-freedom simulation. The goal of this thesis is to demonstrate the utility of Linear Covariance analysis to responsive space mission planning. This is accomplished by first explaining the mathematics that underlie the method. Next the software used for the analysis, Lincov Tools, is explained in detail, the mission is examined more closely, and the hardware for both the payload and launch vehicle are briefly discussed. Finally, the combination of the three degree-of-freedom simulation and Lincov Tools are employed to the space mission and the results are presented.by Benjamin Lee Visser.S.M

The influence of pregnancy on the pharmacokinetic properties of artemisinin combination therapy (ACT): a systematic review

Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy (ACT). However, small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies. The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. A PROSPERO-registered systematic review to identify clinical trials that investigated the influence of pregnancy on the pharmacokinetic properties of different forms of ACT was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2015. The following components of ACT that are currently recommend by the World Health Organization as first-line treatment of malaria in pregnancy were reviewed: artemisinin, artesunate, dihydroartemisinin, lumefantrine, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, piperaquine, atovaquone and proguanil. The literature search identified 121 reports, 27 original studies were included. 829 pregnant women were included in the analysis. Comparison of the available studies showed lower maximum concentrations (Cmax) and exposure (AUC) of dihydroartemisinin, the active metabolite of all artemisinin derivatives, after oral administration of artemether, artesunate and dihydroartemisinin in pregnant women. Low day 7 concentrations were commonly seen in lumefantrine studies, indicating a low exposure and possibly reduced efficacy. The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinically relevant. Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy, while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence. For atovaquone, the available data showed a lower maximum concentration and exposure. Finally, the maximum concentration of cycloguanil, the active metabolite of proguanil, was significantly lower, possibly compromising the efficacy. These findings suggest that reassessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women. However, for most components of ACT, data were insufficient and extensive research with larger sample sizes will be necessary to identify the exact influences of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. In addition, different clinical studies used diverse study designs with various reported relevant outcomes. Future pharmacokinetic studies could benefit from more uniform designs, in order to increase quality, robustness and effectiveness. CRD42015023756 (PROSPERO

Comparison of three local frame definitions for the kinematic analysis of the fingers and the wrist

International audienceBecause the hand is a complex poly-articular limb, numerous methods have been proposed to investigate its kinematics therefore complicating the comparison between studies and the methodological choices. With the objective of overcoming such issues, the present study compared the effect of three local frame definitions on local axis orientations and joint angles of the fingers and the wrist. Three local frames were implemented for each segment. The “Reference” frames were aligned with global axes during a static neutral posture. The “Landmark” frames were computed using palpated bony landmarks. The “Functional” frames included a flexion–extension axis estimated during functional movements. These definitions were compared with regard to the deviations between obtained local segment axes and the evolution of joint (Cardan) angles during two test motions. Each definition resulted in specific local frame orientations with deviations of 15° in average for a given local axis. Interestingly, these deviations produced only slight differences (below 7°) regarding flexion–extension Cardan angles indicating that there is no preferred method when only interested in finger flexion–extension movements. In this case, the Reference method was the easiest to implement, but did not provide physiological results for the thumb. Using the Functional frames reduced the kinematic cross-talk on the secondary and tertiary Cardan angles by up to 20° indicating that the Functional definition is useful when investigating complex three-dimensional movements. Globally, the Landmark definition provides valuable results and, contrary to the other definitions, is applicable for finger deformities or compromised joint rotations

Anatomical parameters for musculoskeletal modeling of the hand and wrist

International audienceA musculoskeletal model of the hand and wrist can provide valuable biomechanical and neurophysiological insights, relevant for clinicians and ergonomists. Currently, no consistent data-set exists comprising the full anatomy of these upper extremity parts. The aim of this study was to collect a complete anatomical data-set of the hand and wrist, including the intrinsic and extrinsic muscles. One right lower arm, taken from a fresh frozen female specimen, was studied. Geometrical data for muscles and joints were digitized using a 3D optical tracking system. For each muscle, optimal fiber length and physiological cross-sectional area were assessed based on muscle belly mass, fiber length, and sarcomere length. A brief description of model, in which these data were imported as input, is also provided. Anatomical data including muscle morphology and joint axes (48 muscles and 24 joints) and mechanical representations of the hand are presented. After incorporating anatomical data in the presented model, a good consistency was found between outcomes of the model and the previous experimental studies

Molecular clouds under the influence of massive stars in the Galactic HII region G353.2+0.9

The Galactic HII region G353.2+0.9 is excited by the massive open cluster Pismis-24. By analyzing (sub-)mm molecular-line and -continuum we study the detailed morphology of the gas and dust, as well as their physical parameters and their variation across the PDR. We observed various molecules and transitions to derive the physical properties of the molecular gas through line ratios, and both LTE and non-LTE analyses. The physical properties of the gas were derived with a Bayesian approach for the non-LTE analysis. Based on the continuum data at 870 micron, we derived the dust mass and the column density of H2, and thus the molecular abundances. The total mass of the gas in the region is ca. 2000 Mo, while that of the dust is ca. 21 Mo. A velocity gradient in the region suggests that the expansion of the ionized gas is pushing the molecular gas away from the observer. We unambiguously identify the ionization front, at the location of which we detect an increase in gas density and temperature. We find at least 14 clumps at different positions and LSR velocities. We derive kinetic temperatures in the ranges 11-45 K (CS) and 20-45 K (CN). The H2 number density is typically around 1e5 cm^-3 from CS and few 1e5 cm^-3 from CN, with maxima above 1e6 cm^-3. The abundances of the molecules observed vary across the region, and appear to be higher in regions further away from the ionization front.Comment: 14 pages, 11 figures. Accepted for publication in Astronomy and Astrophysic

Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature

Summary Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes

Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality

Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults.

Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAPK pathway genes. BRAFV600E mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arises from hematopoietic stem cells (HSCs), nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAFV600E allele-specific polymerase chain reaction was used to map the neoplastic clone in 20 adults with LCH, ECD, and HCL. BRAFV600E was tracked to classical monocytes, nonclassical monocytes, and CD1c+ myeloid dendritic cells (DCs) in the blood, and mutations were observed in HSCs and myeloid progenitors in the bone marrow of 4 patients. The pattern of involvement of peripheral blood myeloid cells was indistinguishable between LCH and ECD, although the histiocytic disorders were distinct to HCL. As reported in children, detection of BRAFV600E in peripheral blood of adults was a marker of active multisystem LCH. The healthy counterparts of myeloid cells affected by BRAF mutation had a range of differentiation potentials depending on exogenous signals. CD1c+ DCs acquired high langerin and CD1a with granulocyte-macrophage colony-stimulating factor and transforming growth factor β alone, whereas CD14+ classical monocytes required additional notch ligation. Both classical and nonclassical monocytes, but not CD1c+ DCs, made foamy macrophages easily in vitro with macrophage colony-stimulating factor and human serum. These studies are consistent with a hematopoietic origin and >1 immediate cellular precursor in both LCH and ECD