1,276 research outputs found
Agro-Exports and the Rural Resource Poor in Latin America: Policy Options for Achieving Broadly Based Growth
Concentrating on fundamental sector-level impacts that shape the nature of agro-export growth, this paper indicates how intrahousehold impacts fit into the analysis. Section 1 is introductory. Section 2 puts forward the conceptual framework needed to understand sectoral impacts of agro-export growth on the rural resource poor, impacts that can be divided into a small-farm adoption effect, a land-access effect, and a labor-absorption effect, all of which are interlinked. Section 3 explores the economic forces that shape the magnitude of the direct (adoption and land access) and indirect (labor absorption) effects of agro-export growth. Its chief message is that the agronomic and economic characteristics of agro-export crops interact with the intrinsic imperfections of rural factor markets to create farm-size biases-biases that are frequently tilted against small farm production. Section 4 summarizes the coordinated empirical, farm-level research on agro-export booms in Chile, Guatemala, and Paraguay. Section 5 analyzes the range of policy available to foment broadly based growth. In order of increasing policy activism, policies are divided into those that (1) get prices and institutions "right," (2) pick winners for public investment, (3) reform land markets, and (4) reform information-constrained markets. Section 5 argues that capital and insurance market reforms will almost always be necessary if agro-export growth is to be broadly based. Section 6 closes the paper with a brief reflection on the desirability of promoting broadly based growth: Is pursuit of broadly based growth worth it given the likely complexity of the recommended factor market interventions? While this is a highly complex and value-laden question, section 6 suggests perspectives from both the U.S. domestic and low-income country policy contexts that make broadly based growth a goal worth pursuing.Community/Rural/Urban Development, International Relations/Trade,
Host Restriction Phenotypes of \u3cem\u3eSalmonella typhi\u3c/em\u3e and \u3cem\u3eSalmonella gallinarum\u3c/em\u3e
Salmonella typhi and Salmonella gallinarum phenotypes correlated with mouse host restriction have been identified by using in vitro and in vivo systems. S. typhi is capable of entering the murine intestinal epithelium via M cells, as is Salmonella typhimurium, which causes systemic infection in the mouse. But, unlike S. typhimurium, S. typhi does not destroy the epithelium and is cleared from the Peyer’s patches soon after M-cell entry. S. gallinarum appears to be incapable of entering the murine Peyer’s patch epithelium. Our in vitro evidence suggests that S. gallinarum is taken up in murine phagocytic cells by a mechanism different from that of S. typhimurium. S. typhimurium is taken up at a higher frequency and is maintained at higher viable counts throughout a 24-h time course in a murine macrophage-like cell line than are S. gallinarum and S. typhi
Rare copy number variations are associated with poorer cognition in schizophrenia
Background
Cognitive impairment in schizophrenia is a major contributor to poor outcomes yet its causes are poorly understood. Some rare copy number variants (CNVs) are associated with schizophrenia risk and impact cognition in healthy populations but their contribution to cognitive impairment in schizophrenia has not been investigated. We examined the effect of 12 schizophrenia CNVs on cognition in those with schizophrenia.
Methods
General cognitive ability was measured using the MATRICS composite z-score in 875 schizophrenia cases, and in a replication sample of 519 schizophrenia cases using WAIS Full-Scale IQ. Using linear regression we tested for association between cognition and schizophrenia CNV status, covarying for age and sex. In addition, we tested whether CNVs hitting genes in schizophrenia enriched gene sets (loss of function intolerant or synaptic gene sets) were associated with cognitive impairment.
Results
23 schizophrenia CNV carriers were identified. Schizophrenia CNV carriers had lower general cognitive ability than non-schizophrenia CNV carriers in discovery (β=-0.66, 95%CI = -1.31 to -0.01) and replication samples (β=-0.91, 95%CI =-1.71 to -0.11), and after meta-analysis (β=-0.76, 95%CI=-1.26 to -0.25, p=0.003). CNVs hitting loss of function intolerant genes were associated with lower cognition (β= -0.15, 95%CI=-0.29 to -0.001, p=0.048).
Conclusions
In those with schizophrenia, cognitive ability in schizophrenia CNV carriers is 0.5-1.0 standard deviations below non-CNV carriers, which may have implications for clinical assessment and management. We also demonstrate that rare CNVs hitting genes intolerant to loss of function variation lead to more severe cognitive impairment, above and beyond the effect of known schizophrenia CNVs
Detection of Mycobacterium tuberculosis in Sputum by Gas Chromatography-Mass Spectrometry of Methyl Mycocerosates Released by Thermochemolysis
Tuberculosis requires rapid diagnosis to prevent further transmission and allow prompt administration of treatment. Current methods for diagnosing pulmonary tuberculosis lack sensitivity are expensive or are extremely slow. The identification of lipids using gas chromatography- electron impact mass spectrometry (GC-EI/MS) could provide an alternative solution. We have studied mycocerosic acid components of the phthiocerol dimycocerosate (PDIM) family of lipids using thermochemolysis GC-EI/MS. To facilitate use of the technology in a routine diagnostic laboratory a simple extraction procedure was employed where PDIMs were extracted from sputum using petroleum ether, a solvent of low polarity. We also investigated a method using methanolic tetramethylammonium hydroxide, which facilitates direct transesterification of acidic components to methyl esters in the inlet of the GC-MS system. This eliminates conventional chemical manipulations allowing rapid and convenient analysis of samples. When applied to an initial set of 40 sputum samples, interpretable results were obtained for 35 samples with a sensitivity relative to culture of 94% (95%CI: 69.2,100) and a specificity of 100% (95%CI: 78.1,100). However, blinded testing of a larger set of 395 sputum samples found the assay to have a sensitivity of 61.3% (95%CI: 54.9,67.3) and a specificity of 70.6% (95%CI: 62.3,77.8) when compared to culture. Using the results obtained we developed an improved set of classification criteria, which when applied in a blinded re-analysis increased the sensitivity and specificity of the assay to 64.9% (95%CI: 58.6,70.8) and 76.2% (95%CI: 68.2,82.8) respectively. Highly variable levels of background signal were observed from individual sputum samples that inhibited interpretation of the data. The diagnostic potential of using thermochemolytic GC-EI/MS of PDIM biomarkers for diagnosis of tuberculosis in sputum has been established; however, further refinements in sample processing are required to enhance the sensitivity and robustness of the test
Results of a randomized, double blind, placebo controlled, crossover trial of melatonin for treatment of Nocturia in adults with multiple sclerosis (MeNiMS)
© 2018 The Author(s). Background: Nocturia is a common urinary symptom of multiple sclerosis (MS) which can affect quality of life (QoL) adversely. Melatonin is a hormone known to regulate circadian rhythm and reduce smooth muscle activity such as in the bladder. There is limited evidence supporting use of melatonin to alleviate urinary frequency at night in the treatment of nocturia. The aim of this study was to evaluate the effect of melatonin on the mean number of nocturia episodes per night in patients with MS. Methods: A randomized, double blind, placebo controlled crossover trial was conducted. 34 patients with nocturia secondary to multiple sclerosis underwent a 4-day pre-treatment monitoring phase. The patients were randomized to receive either 2 mg per night (taken at bedtime) of capsulated sustained-release melatonin (Circadin®) or 1 placebo capsule for 6 weeks followed by a crossover to the other regimen for an additional 6 weeks after a 1-month washout period. Results: From the 26 patients who completed the study, there was no significant difference observed in the signs or symptoms of nocturia when taking 2 mg melatonin compared to placebo. The primary outcome measure, mean number of nocturia episodes on bladder diaries, was 1.8/night at baseline, and 1.4/night on melatonin, compared with 1.6 for placebo (Medians 1.70, 1.50, and 1.30 respectively, p = 0.85). There was also no significant difference seen in LUTS, QoL and sleep quality when taking melatonin. No significant safety concerns arose. Conclusions: This small study suggests that a low dose of melatonin taken at bedtime may be ineffective therapy for nocturia in MS. Trial registration: (EudraCT reference) 2012-00418321 registered: 25/01/13. ISRCTN Registry: ISRCTN38687869
Macrovertebrate Paleontology and the Pliocene Habitat of Ardipithecus ramidus
International audienceA diverse assemblage of large mammals is spatially and stratigraphically associated with Ardipithecus ramidus at Aramis. The most common species are tragelaphine antelope and colobine monkeys. Analyses of their postcranial remains situate them in a closed habitat. Assessment of dental mesowear, microwear, and stable isotopes from these and a wider range of abundant associated larger mammals indicates that the local habitat at Aramis was predominantly woodland. The Ar. ramidus enamel isotope values indicate a minimal C4 vegetation component in its diet (plants using the C4 photosynthetic pathway), which is consistent with predominantly forest/woodland feeding. Although the Early Pliocene Afar included a range of environments, and the local environment at Aramis and its vicinity ranged from forests to wooded grasslands, the integration of available physical and biological evidence establishes Ar. ramidus as a denizen of the closed habitats along this continuum
Human and mouse essentiality screens as a resource for disease gene discovery
The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery
Observing Antarctic Bottom Water in the Southern Ocean
Dense, cold waters formed on Antarctic continental shelves descend along the Antarctic continental margin, where they mix with other Southern Ocean waters to form Antarctic Bottom Water (AABW). AABW then spreads into the deepest parts of all major ocean basins, isolating heat and carbon from the atmosphere for centuries. Despite AABW’s key role in regulating Earth’s climate on long time scales and in recording Southern Ocean conditions, AABW remains poorly observed. This lack of observational data is mostly due to two factors. First, AABW originates on the Antarctic continental shelf and slope where in situ measurements are limited and ocean observations by satellites are hampered by persistent sea ice cover and long periods of darkness in winter. Second, north of the Antarctic continental slope, AABW is found below approximately 2 km depth, where in situ observations are also scarce and satellites cannot provide direct measurements. Here, we review progress made during the past decades in observing AABW. We describe 1) long-term monitoring obtained by moorings, by ship-based surveys, and beneath ice shelves through bore holes; 2) the recent development of autonomous observing tools in coastal Antarctic and deep ocean systems; and 3) alternative approaches including data assimilation models and satellite-derived proxies. The variety of approaches is beginning to transform our understanding of AABW, including its formation processes, temporal variability, and contribution to the lower limb of the global ocean meridional overturning circulation. In particular, these observations highlight the key role played by winds, sea ice, and the Antarctic Ice Sheet in AABW-related processes. We conclude by discussing future avenues for observing and understanding AABW, impressing the need for a sustained and coordinated observing system
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
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