Development of an improved protective cover/light block for multilayer insulation

The feasibility of using a scrim-reinforced, single metallized, 4-mil Tedlar film as a replacement for the Teflon coated Beta-cloth/single metallized 3-mil Kapton film presently used as the protective cover/light block for multilayer insulation (MLI) on the Orbiter, Spacelab, and other space applications was demonstrated. The proposed Tedlar concept is lighter and potentially lower in cost. Thermal analysis with the proper concept was much simpler than with the present system. Tests have already demonstrated that white Tedlar has low alpha (adsorption) degradation in space from U.V. The proposed concept was 4400 percent cheaper with nominal weight savings of 50 percent

Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia

Objectives To assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia. Design Cost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated. Participants Simulated population aged 16­54 years in England and Wales. Interventions Identification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients. Main outcome measure Cost effectiveness calculated as cost per life year gained (extension of life expectancy resulting from intervention) including estimated costs of screening and treatment. Results Tracing of family members was the most cost effective strategy (£3097 (&5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of £133 per case detected. If the genetic mutation was known within the family then the cost per life year gained (£4914) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (£13 029 per life year gained) as 1365 individuals need to be screened at a cost of £9754 per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (£2777 with a clinical confirmation). Conclusions Screening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population

Is there an integrative center in the vertebrate brain-stem? A robotic evaluation of a model of the reticular formation viewed as an action selection device

Neurobehavioral data from intact, decerebrate, and neonatal rats, suggests that the reticular formation provides a brainstem substrate for action selection in the vertebrate central nervous system. In this article, Kilmer, McCulloch and Blum’s (1969, 1997) landmark reticular formation model is described and re-evaluated, both in simulation and, for the first time, as a mobile robot controller. Particular model configurations are found to provide effective action selection mechanisms in a robot survival task using either simulated or physical robots. The model’s competence is dependent on the organization of afferents from model sensory systems, and a genetic algorithm search identified a class of afferent configurations which have long survival times. The results support our proposal that the reticular formation evolved to provide effective arbitration between innate behaviors and, with the forebrain basal ganglia, may constitute the integrative, ’centrencephalic’ core of vertebrate brain architecture. Additionally, the results demonstrate that the Kilmer et al. model provides an alternative form of robot controller to those usually considered in the adaptive behavior literature

A Note On Fixed-point Theorems

In an earlier note, S. P. Singh gave an extension of a theorem of Brosowski in a normed linear space setting. Variants of this theorem are considered in the context of strictly convex, reflexive, and inner product spaces. © 1982

The continued value of disk diffusion for assessing antimicrobial susceptibility in clinical laboratories: Report from the Clinical and Laboratory Standards Institute Methods Development and Standardization Working Group

Expedited pathways to antimicrobial agent approval by the U.S. Food and Drug Administration (FDA) have led to increased delays between drug approval and the availability of FDA-cleared antimicrobial susceptibility testing (AST) devices.</jats:p

Cardiovascular risk stratification in familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a common autosomal-dominant disorder in most European countries. Patients with FH are characterised by a raised level of low-density lipoprotein cholesterol and a high risk of premature coronary heart disease (CHD). Currently there is no consensus regarding the clinical utility to predict future coronary events or testing for the presence of subclinical atherosclerotic disease in asymptomatic patients with FH. Family screening of patients with FH as recommended by the UK National Institute of Health and Care Excellence guideline would result in finding many young individuals with a diagnosis of FH who are clinically asymptomatic. The traditional CHD risk scores, that is, the Framingham score, are insufficient in risk prediction in this group of young individuals. In addition, a better understanding of the genetic aetiology of the FH phenotype and CHD risk in monogenic FH and polygenic hypercholesterolaemia is needed. Non-invasive imaging methods such as carotid intima-media thickness measurement might produce more reliable information in finding high-risk patients with FH. The potential market authorisation of novel therapeutic agents such as PCSK9 monoclonal inhibitors makes it essential to have a better screening programme to prioritise the candidates for treatment with the most severe form of FH and at higher risk of coronary events. The utility of new imaging techniques and new cardiovascular biomarkers remains to be determined in prospective trials

Modular deconstruction reveals the dynamical and physical building blocks of a locomotion motor program

The neural substrates of motor programs are only well understood for small, dedicated circuits. Here we investigate how a motor program is constructed within a large network. We imaged populations of neurons in the Aplysia pedal ganglion during execution of a locomotion motor program. We found that the program was built from a very small number of dynamical building blocks, including both neural ensembles and low-dimensional rotational dynamics. These map onto physically discrete regions of the ganglion, so that the motor program has a corresponding modular organization in both dynamical and physical space. Using this dynamic map, we identify the population potentially implementing the rhythmic pattern generator and find that its activity physically traces a looped trajectory, recapitulating its low-dimensional rotational dynamics. Our results suggest that, even in simple invertebrates, neural motor programs are implemented by large, distributed networks containing multiple dynamical systems

Activation of Bax in Three Models of Retinitis Pigmentosa

PURPOSE:The process of photoreceptor cell death in retinitis pigmentosa is still not well characterized, and identification of common mechanisms will be instrumental for development of therapeutic strategies. Here we investigated activation of Bax in rd1, P23H transgenic, and Rho knockout retinas. METHODS:Bax activation was evaluated by immunofluorescence using anti-activated Bax-specific antibodies and by Western blotting on mitochondrial protein extracts. Knockdown of cathepsin D, calpain 1, and calpain 2 was achieved by short hairpin RNA (shRNA) delivery in rd1 mutant photoreceptors cells differentiated from retinal neurospheres. The mechanism of Bax activation through calpains was evaluated in vivo by intravitreal injection of calpastatin. RESULTS:We defined activation and mitochondrial localization of Bax as well as activation of calpains and cathepsin D in the three models of retinitis pigmentosa. Taking advantage of an in vitro culture system for rd1 mutant photoreceptors, we unraveled the mechanism of Bax activation. We demonstrated that calpain 1 and cathepsin D contributed to activation of Bax and to apoptosis-inducing factor (Aif) nuclear translocation. In vivo interference with calpain activity blocks Bax activation in the rd1 and Rho knockout retinas and reduces activation in the P23H transgenic retina. CONCLUSIONS:Activation of Bax was observed in all three models of retinitis pigmentosa and leads to neurodamage by localization at the mitochondrion. Our data suggest that Bax can be envisaged as one of the promising target molecules for restraining photoreceptor degeneration