Technical assessment of Mir-1 life support hardware for the international space station

NASA has been progressively learning the design and performance of the Russian life support systems utilized in their Mir space station. In 1992, a plan was implemented to assess the benefits of the Mir-1 life support systems to the Freedom program. Three primary tasks focused on: evaluating the operational Mir-1 support technologies and understanding if specific Russian systems could be directly utilized on the American space station and if Russian technology design information could prove useful in improving the current design of the planned American life support equipment; evaluating the ongoing Russian life support technology development activities to determine areas of potential long-term application to the U.S. space station; and utilizing the expertise of their space station life support systems to evaluate the benefits to the current U.S. space station program which included the integration of the Russian Mir-1 designs with the U.S. designs to support a crew of six

Submerged in the mainstream? A case study of an immigrant learner in a New Zealand primary classroom

Immigrant children from diverse language backgrounds face not only linguistic challenges when enrolled in mainstream English-medium classrooms, but also difficulties adjusting to an unfamiliar learning community. The culture of primary school classrooms in New Zealand typically reflects conventions across three dimensions: interactional, instructional task performance and cognitive-academic development. All three dimensions are underpinned by the culturally specific discourse conventions involved in language socialisation. New learners may be helped by classmates or their teacher to understand and successfully use these conventions, but left on their own they may sink rather than swim. This is a case study of one Taiwanese 11-year old boy, 'John', who entered a New Zealand primary classroom midway through the school year. John's basic conversational ability was sound, but he did not possess the interactive classroom skills needed to operate in the new culture of learning. Selected from a wider study of the classroom, transcript data from audio-recorded excerpts of John's interactions over several months with his teacher and classmates are interpreted from perspectives derived from sociocultural and language socialisation theories. The article concludes with a brief consideration of the extent to which John constructed, or was constrained from constructing meaningful learning experiences, and suggestions for further research and reflection

Child health insurance coverage: a survey among temporary and permanent residents in Shanghai

<p>Abstract</p> <p>Background</p> <p>Under the current healthcare system in China, there is no government-sponsored health insurance program for children. Children from families who move from rural and interior regions to large urban centres without a valid residency permit might be at higher risk of being uninsured due to their low socioeconomic status. We conducted a survey in Shanghai to describe children's health insurance coverage according to their migration status.</p> <p>Method</p> <p>Between 2005 and 2006, we conducted an in-person health survey of the adult care-givers of children aged 7 and under, residing in five districts of Shanghai. We compared uninsurance rates between temporary and permanent child residents, and investigated factors associated with child health uninsurance.</p> <p>Results</p> <p>Even though cooperative insurance eligibility has been extended to temporary residents of Shanghai, the uninsurance rate was significantly higher among temporary (65.6%) than permanent child residents (21.1%, adjusted odds ratio (OR): 5.85, 95% confidence interval (95% CI): 4.62–7.41). For both groups, family income was associated with having child health insurance; children in lower income families were more likely to be uninsured (OR: 1.96, 95% CI: 1.40–2.96).</p> <p>Conclusion</p> <p>Children must rely on their parents to make the insurance purchase decision, which is constrained by their income and the perceived benefits of the insurance program. Children from migrant families are at even higher risk for uninsurance due to their lower socioeconomic status. Government initiatives specifically targeting temporary residents and providing health insurance benefits for their children are urgently needed.</p

Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study

<p>Abstract</p> <p>Background</p> <p>A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near <it>MS4A4A, CD2AP, EPHA1 </it>and <it>CD33</it>. Meta-analyses of this and a previously published GWAS revealed significant association at <it>ABCA7 </it>and <it>MS4A</it>, independent evidence for association of <it>CD2AP, CD33 </it>and <it>EPHA1 </it>and an opposing yet significant association of a variant near <it>ARID5B</it>. In this study, we genotyped five variants (in or near <it>CD2AP, EPHA1, ARID5B</it>, and <it>CD33</it>) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and <it>APOE ε4 </it>dosage.</p> <p>Results</p> <p>We found no significant evidence of series heterogeneity. Associations with LOAD were successfully replicated for <it>EPHA1 </it>(rs11767557; OR = 0.87, p = 5 × 10^-4) and <it>CD33 </it>(rs3865444; OR = 0.92, p = 0.049), with odds ratios comparable to those previously reported. Although the two <it>ARID5B </it>variants (rs2588969 and rs494288) showed significant association with LOAD in meta-analysis of our dataset (p = 0.046 and 0.008, respectively), the associations did not survive adjustment for covariates (p = 0.30 and 0.11, respectively). We had insufficient evidence in our data to support the association of the <it>CD2AP </it>variant (rs9349407, p = 0.56).</p> <p>Conclusions</p> <p>Our data overwhelmingly support the association of <it>EPHA1 </it>and <it>CD33 </it>variants with LOAD risk: addition of our data to the results previously reported (total n > 42,000) increased the strength of evidence for these variants, providing impressive p-values of 2.1 × 10^-15(<it>EPHA1</it>) and 1.8 × 10^-13(<it>CD33</it>).</p

The Effects of Tail Biopsy for Genotyping on Behavioral Responses to Nociceptive Stimuli

Removal of a small segment of tail at weaning is a common method used to obtain tissue for the isolation of genomic DNA to identify genetically modified mice. When genetically manipulated mice are used for pain research, this practice could result in confounding changes to the animals' responses to noxious stimuli. In this study, we sought to systematically investigate whether tail biopsy representative of that used in standard genotyping methods affects behavioral responses to a battery of tests of nociception. Wild-type littermate C57BL/6J and 129S6 female and male mice received either tail biopsies or control procedural handling at Day 21 after birth and were then tested at 6–9 weeks for mechanical and thermal sensitivity. C57BL/6J mice were also tested in the formalin model of inflammatory pain. In all tests performed (von Frey, Hargreaves, modified Randall Selitto, and formalin), C57BL/6J tail-biopsied animals' behavioral responses were not significantly different from control animals. In 129S6 animals, tail biopsy did not have a significant effect on behavioral responses in either sex to the von Frey and the modified Randall-Selitto tests of mechanical sensitivity. Interestingly, however, both sexes exhibited small but significant differences between tail biopsied and control responses to a radiant heat stimulus. These results indicate that tail biopsy for genotyping purposes has no effect on nocifensive behavioral responses of C57BL/6J mice, and in 129S6 mice, causes only a minor alteration in response to a radiant heat stimulus while other nocifensive behavioral responses are unchanged. The small effect seen is modality- and strain-specific

English language proficiency and the accommodations for language non-concordance amongst patients utilizing chiropractic college teaching clinics

Background: The number of households in the United States that are not proficient in the English language is growing and presenting a challenge to the health care system. Over nineteen percent of the US population speak a language other than English in the home. This increase in language discordance generates a greater need to find and implement accommodations in the clinical setting to insure accurate and efficient diagnosis and treatment as well as provide for patient safety. Aim: The purpose of this study is to determine the percentage of patients accessing the chiropractic college teaching clinics who are not proficient in the English language and to what extent the colleges provide accommodations for that language disparity. Methods: The clinic directors and deans of the Association of Chiropractic Colleges were surveyed via an on-line survey engine. The survey queried the percentage of the patient population that is not English language proficient, the accommodations the college currently has in place, if the college has a language specific consent to treat document and if the college has a written policy concerning patients without English proficiency. Results: Fifty percent of the contacted chiropractic colleges responded to the survey. In the respondent college clinics 16.5% of the patient population is not proficient in English, with over 75% speaking Spanish. All but one of the respondents provide some level of accommodation for the language non-concordance. Forty five percent of the responding colleges employ a language specific consent to treat form. The implementation of accommodations and the use of a language specific consent to treat form is more prevalent at colleges with a higher percentage of non-English speaking patients. Conclusions: The percentage of patients with limited English proficiency accessing services at the teaching clinics of the chiropractic colleges mirrors the numbers in the general population. There is a wide disparity in the accommodations that the individual colleges make to address this language discordance. There is a need to further develop accurate and meaningful accommodations to address language disparity in the chiropractic teaching clinics.https://doi.org/10.1186/2045-709X-21-

High-Order SNP Combinations Associated with Complex Diseases: Efficient Discovery, Statistical Power and Functional Interactions

There has been increased interest in discovering combinations of single-nucleotide polymorphisms (SNPs) that are strongly associated with a phenotype even if each SNP has little individual effect. Efficient approaches have been proposed for searching two-locus combinations from genome-wide datasets. However, for high-order combinations, existing methods either adopt a brute-force search which only handles a small number of SNPs (up to few hundreds), or use heuristic search that may miss informative combinations. In addition, existing approaches lack statistical power because of the use of statistics with high degrees-of-freedom and the huge number of hypotheses tested during combinatorial search. Due to these challenges, functional interactions in high-order combinations have not been systematically explored. We leverage discriminative-pattern-mining algorithms from the data-mining community to search for high-order combinations in case-control datasets. The substantially improved efficiency and scalability demonstrated on synthetic and real datasets with several thousands of SNPs allows the study of several important mathematical and statistical properties of SNP combinations with order as high as eleven. We further explore functional interactions in high-order combinations and reveal a general connection between the increase in discriminative power of a combination over its subsets and the functional coherence among the genes comprising the combination, supported by multiple datasets. Finally, we study several significant high-order combinations discovered from a lung-cancer dataset and a kidney-transplant-rejection dataset in detail to provide novel insights on the complex diseases. Interestingly, many of these associations involve combinations of common variations that occur in small fractions of population. Thus, our approach is an alternative methodology for exploring the genetics of rare diseases for which the current focus is on individually rare variations

Fine mapping of the 9q31 Hirschsprung’s disease locus

Hirschsprung’s disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 × 10−6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCR-association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system

Antihyperalgesia by α2-GABAA Receptors Occurs Via a Genuine Spinal Action and Does Not Involve Supraspinal Sites

Drugs that enhance GABAergic inhibition alleviate inflammatory and neuropathic pain after spinal application. This antihyperalgesia occurs mainly through GABAA receptors (GABAARs) containing α2 subunits (α2-GABAARs). Previous work indicates that potentiation of these receptors in the spinal cord evokes profound antihyperalgesia also after systemic administration, but possible synergistic or antagonistic actions of supraspinal α2-GABAARs on spinal antihyperalgesia have not yet been addressed. Here we generated two lines of GABAAR-mutated mice, which either lack α2-GABAARs specifically from the spinal cord, or, which express only benzodiazepine-insensitive α2-GABAARs at this site. We analyzed the consequences of these mutations for antihyperalgesia evoked by systemic treatment with the novel non-sedative benzodiazepine site agonist HZ166 in neuropathic and inflammatory pain. Wild-type mice and both types of mutated mice had similar baseline nociceptive sensitivities and developed similar hyperalgesia. However, antihyperalgesia by systemic HZ166 was reduced in both mutated mouse lines by about 60% and was virtually indistinguishable from that of global point-mutated mice, in which all α2-GABAARs were benzodiazepine insensitive. The major (α2-dependent) component of GABAAR-mediated antihyperalgesia was therefore exclusively of spinal origin, whereas supraspinal α2-GABAARs had neither synergistic nor antagonistic effects on antihyperalgesia. Our results thus indicate that drugs that specifically target α2-GABAARs exert their antihyperalgesic effect through enhanced spinal nociceptive control. Such drugs may therefore be well-suited for the systemic treatment of different chronic pain conditions