Transmission Spectra of Transiting Planet Atmospheres: Model Validation and Simulations of the Hot Neptune GJ 436b for JWST

We explore the transmission spectrum of the Neptune-class exoplanet GJ 436b, including the possibility that its atmospheric opacity is dominated by a variety of non- equilibrium chemical products. We also validate our transmission code by demonstrating close agreement with analytic models that use only Rayleigh scattering or water vapor opacity. We find broad disagreement with radius variations predicted by another published model. For GJ 436b, the relative coolness of the planet's atmosphere, along with its implied high metallicity, may make it dissimilar in character compared to "hot Jupiters." Some recent observational and modeling efforts suggest low relative abundances of H2O and CH4 present in GJ 436b's atmosphere, compared to calculations from equilibrium chemistry. We include these characteristics in our models and examine the effects of absorption from methane-derived higher order hydrocarbons. Significant absorption from HCN and C2H2 are found throughout the infrared, while C2H4 and C2H6 are less easily seen. We perform detailed simulations of JWST observations, including all likely noise sources, and find that we will be able to constrain chemical abundance regimes from this planet's transmission spectrum. For instance, the width of the features at 1.5, 3.3, and 7 microns indicates the amount of HCN versus C2H2 present. The NIRSpec prism mode will be useful due to its large spectral range and the relatively large number of photo-electrons recorded per spectral resolution element. However, extremely bright host stars like GJ 436 may be better observed with a higher spectroscopic resolution mode in order to avoid detector saturation. We find that observations with the MIRI low resolution spectrograph should also have high signal-to-noise in the 5 - 10 micron range due to the brightness of the star and the relatively low spectral resolution (R ~ 100) of this mode.Comment: 33 pages, 12 figures, Accepted to Ap

The family as a determinant of stunting in children living in conditions of extreme poverty: a case-control study

BACKGROUND: Malnutrition in children can be a consequence of unfavourable socioeconomic conditions. However, some families maintain adequate nutritional status in their children despite living in poverty. The aim of this study was to ascertain whether family-related factors are determinants of stunting in young Mexican children living in extreme poverty, and whether these factors differ between rural or urban contexts. METHODS: A case-control study was conducted in one rural and one urban extreme poverty level areas in Mexico. Cases comprised stunted children aged between 6 and 23 months. Controls were well-nourished children. Independent variables were defined in five dimensions: family characteristics; family income; household allocation of resources and family organisation; social networks; and child health care. Information was collected from 108 cases and 139 controls in the rural area and from 198 cases and 211 controls in the urban area. Statistical analysis was carried out separately for each area; unconditional multiple logistic regression analyses were performed to obtain the best explanatory model for stunting. RESULTS: In the rural area, a greater risk of stunting was associated with father's occupation as farmer and the presence of family networks for child care. The greatest protective effect was found in children cared for exclusively by their mothers. In the urban area, risk factors for stunting were father with unstable job, presence of small social networks, low rate of attendance to the Well Child Program activities, breast-feeding longer than six months, and two variables within the family characteristics dimension (longer duration of parents' union and migration from rural to urban area). CONCLUSIONS: This study suggests the influence of the family on the nutritional status of children under two years of age living in extreme poverty areas. Factors associated with stunting were different in rural and urban communities. Therefore, developing and implementing health programs to tackle malnutrition should take into account such differences that are consequence of the social, economic, and cultural contexts in which the family lives

Lacticacidaemia due to pyruvate dehydrogenase deficiency, with evidence of protein polymorphism in the α-subunit of the enzyme

In three infants with neonatal lacticacidaemia, a deficiency in the E 1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex was demonstrated in skin fibroblast cultures. Residual activites of the pyruvate dehydrogenase complex in the activated state were 1.6%, 3.9% and 18.8% of control values, respectively. Immunoprecipitation of extracts of cultures skin fibroblasts grown on 35 S-methionine with anti-pyruvate dehydrogenase complex antibody revealed an abnormality in the E 1 α-component of these three patients when visualised after sodium dodecyl sulphate/polyacrylamide gel electrophoresis. This component appeared to have a slightly lower molecular weight than did this protein from control cell strains. Cell strains from other patients with a deficiency of the pyruvate dehydrogenase complex did not exhibit this defect. Three patients also showed dysmorphism and developmental abnormalities of the central nervous system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47532/1/431_2004_Article_BF00441736.pd

Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial

Background Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. Methods/design A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. Discussion The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. Trial registration Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015

Nanopore Detector based analysis of single-molecule conformational kinetics and binding interactions

BACKGROUND: A Nanopore Detector provides a means to transduce single molecule events into observable channel current changes. Nanopore-based detection can report directly, or indirectly, on single molecule kinetics. The nanopore-based detector can directly measure molecular characteristics in terms of the blockade properties of individual molecules – this is possible due to the kinetic information that is embedded in the blockade measurements, where the adsorption-desorption history of the molecule to the surrounding channel, and the configurational changes in the molecule itself, imprint on the ionic flow through the channel. This rich source of information offers prospects for DNA sequencing and single nucleotide polymorphism (SNP) analysis. A nanopore-based detector can also measure molecular characteristics indirectly, by using a reporter molecule that binds to certain molecules, with subsequent distinctive blockade by the bound-molecule complex. RESULTS: It is hypothesized that reaction histories of individual molecules can be observed on model DNA/DNA, DNA/Protein, and Protein/Protein systems. Preliminary results are all consistent with this hypothesis. Nanopore detection capabilities are also described for highly discriminatory biosensing, binding strength characterization, and rapid immunological screening. CONCLUSION: In essence, the heart of chemistry is now accessible to a new, single-molecule, observation method that can track both external molecular binding states, and internal conformation states

Interstitial lung disease in children - genetic background and associated phenotypes

Interstitial lung disease in children represents a group of rare chronic respiratory disorders. There is growing evidence that mutations in the surfactant protein C gene play a role in the pathogenesis of certain forms of pediatric interstitial lung disease. Recently, mutations in the ABCA3 transporter were found as an underlying cause of fatal respiratory failure in neonates without surfactant protein B deficiency. Especially in familiar cases or in children of consanguineous parents, genetic diagnosis provides an useful tool to identify the underlying etiology of interstitial lung disease. The aim of this review is to summarize and to describe in detail the clinical features of hereditary interstitial lung disease in children. The knowledge of gene variants and associated phenotypes is crucial to identify relevant patients in clinical practice

Aerosol delivery to ventilated newborn infants: historical challenges and new directions

There are several aerosolized drugs which have been used in the treatment of neonatal respiratory illnesses, such as bronchodilators, diuretics, and surfactants. Preclinical in vitro and in vivo studies identified a number of variables that affect aerosol efficiency, including particle size, aerosol flows, nebulizer choice, and placement. Nevertheless, an optimized aerosol drug delivery system for mechanically ventilated infants still does not exist. Increasing interest in this form of drug delivery requires more controlled and focused research of drug/device combinations appropriate for the neonatal population. In the present article, we review the research that has been conducted thus far and discuss the next steps in developing the optimal aerosol delivery system for use in mechanically ventilated neonates

Nitazoxanide Stimulates Autophagy and Inhibits mTORC1 Signaling and Intracellular Proliferation of Mycobacterium tuberculosis

Tuberculosis, caused by Mycobacterium tuberculosis infection, is a major cause of morbidity and mortality in the world today. M. tuberculosis hijacks the phagosome-lysosome trafficking pathway to escape clearance from infected macrophages. There is increasing evidence that manipulation of autophagy, a regulated catabolic trafficking pathway, can enhance killing of M. tuberculosis. Therefore, pharmacological agents that induce autophagy could be important in combating tuberculosis. We report that the antiprotozoal drug nitazoxanide and its active metabolite tizoxanide strongly stimulate autophagy and inhibit signaling by mTORC1, a major negative regulator of autophagy. Analysis of 16 nitazoxanide analogues reveals similar strict structural requirements for activity in autophagosome induction, EGFP-LC3 processing and mTORC1 inhibition. Nitazoxanide can inhibit M. tuberculosis proliferation in vitro. Here we show that it inhibits M. tuberculosis proliferation more potently in infected human THP-1 cells and peripheral monocytes. We identify the human quinone oxidoreductase NQO1 as a nitazoxanide target and propose, based on experiments with cells expressing NQO1 or not, that NQO1 inhibition is partly responsible for mTORC1 inhibition and enhanced autophagy. The dual action of nitazoxanide on both the bacterium and the host cell response to infection may lead to improved tuberculosis treatment