Interactions between large molecules pose a puzzle for reference quantum mechanical methods

Quantum-mechanical methods are used for understanding molecular interactions throughout the natural sciences. Quantum diffusion Monte Carlo (DMC) and coupled cluster with single, double, and perturbative triple excitations [CCSD(T)] are state-of-the-art trusted wavefunction methods that have been shown to yield accurate interaction energies for small organic molecules. These methods provide valuable reference information for widely-used semi-empirical and machine learning potentials, especially where experimental information is scarce. However, agreement for systems beyond small molecules is a crucial remaining milestone for cementing the benchmark accuracy of these methods. We show that CCSD(T) and DMC interaction energies are not consistent for a set of polarizable supramolecules. Whilst there is agreement for some of the complexes, in a few key systems disagreements of up to 8 kcal mol−1 remain. These findings thus indicate that more caution is required when aiming at reproducible non-covalent interactions between extended molecules

Extraction of bodily features for gait recognition and gait attractiveness evaluation

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11042-012-1319-2. Copyright @ 2012 Springer.Although there has been much previous research on which bodily features are most important in gait analysis, the questions of which features should be extracted from gait, and why these features in particular should be extracted, have not been convincingly answered. The primary goal of the study reported here was to take an analytical approach to answering these questions, in the context of identifying the features that are most important for gait recognition and gait attractiveness evaluation. Using precise 3D gait motion data obtained from motion capture, we analyzed the relative motions from different body segments to a root marker (located on the lower back) of 30 males by the fixed root method, and compared them with the original motions without fixing root. Some particular features were obtained by principal component analysis (PCA). The left lower arm, lower legs and hips were identified as important features for gait recognition. For gait attractiveness evaluation, the lower legs were recognized as important features.Dorothy Hodgkin Postgraduate Award and HEFCE

Low Blood Lead Levels Do Not Appear to Be Further Reduced by Dietary Supplements

OBJECTIVE: Our objective was to evaluate the association of dietary intakes of selected micronutrients and blood lead (PbB) concentrations in female adults and in children. DESIGN: With longitudinal monitoring, we measured daily intakes of the micronutrients calcium, magnesium, sodium, potassium, barium, strontium, phosphorus, zinc, iron (limited data), and copper from 6-day duplicate diets (2–13 collections per individual) and PbB concentrations. Participants were three groups of females of child-bearing age (one cohort consisting of 21 pregnant subjects and 15 nonpregnant controls, a second cohort of nine pregnant migrants), and one group of 10 children 6–11 years of age. RESULTS: Mean PbB concentrations were < 5 μg/dL. A mixed linear model that included only group and time accounted for 5.9% of the variance of the PbB measurements; neither the effect of time nor the effect of group was significant. The model containing all of the micronutrients (except iron, for which there was a great deal of missing data), along with time and group, accounted for approximately 9.2% of the variance of PbB; this increase was not statistically significant. There was, however, a significant association of PbB with phosphorus, magnesium, and copper when all micronutrients were included in the statistical analysis, perhaps reflecting a synergistic effect. CONCLUSIONS: In contrast to most previous studies, we found no statistically significant relationships between the PbB concentrations and micronutrient intake. In adults and older children with low PbB concentrations and minimal exposure to Pb, micronutrient supplementation is probably unnecessary

The Alberta Ambassador Program: delivering Health Technology Assessment results to rural practitioners

BACKGROUND: The purpose of Health Technology Assessment (HTA) is to make the best possible summary of the evidence regarding specific health interventions in order to influence health care and policy decisions. The need for decision makers to find relevant HTA data when it is needed is a barrier to its usefulness. These barriers are highest in rural areas and amongst isolated practitioners. METHODS: A multidisciplinary team developed an interactive case-based instructional strategy on the topic of chronic non-cancer pain (CNCP) management using clinical evidence derived by HTA. The evidence for each of 18 CNCP interventions was distilled into single-sheet summaries. Clinicians and HTA specialists ('Ambassadors') conducted 11 two-hour interactive sessions on CNCP in eight of Alberta's nine health regions. Pre- and post-session evaluations were conducted. RESULTS: The sessions were attended by 130 individuals representing 14 health and administrative disciplines. The ambassador model was well received. The use of content experts as ambassadors was highly rated. The educational strategy was judged to be effective. Awareness of the best evidence in CNCP management was increased. Although some participants reported practice changes as a result of the workshops, the program was not designed to measure changes in patient outcome. CONCLUSION: The ambassador program was successful in increasing awareness of the best evidence in CNCP management, and positively influenced treatment decisions. Its teaching methods were felt to be unique and innovative by participants. Its methods could be applied to other clinical content areas in order to increase the uptake of the results of HTA

A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload

BACKGROUND: It has been recently demonstrated that CD8+ T-lymphocyte numbers are genetically transmitted in association with the MHC class I region. The present study was designed with the objective of narrowing the region associated with the setting of CD8+ T-lymphocyte numbers in a population of C282Y homozygous hemochromatosis subjects, in whom a high prevalence of abnormally low CD8+ T-lymphocyte counts has been described. METHODS: The study includes 43 C282Y homozygous subjects fully characterized both phenotypically and genotypically. Clinical characterization includes measurements of iron parameters at diagnosis (transferrin saturation and serum ferritin), total body iron stores and T-cell immunophenotyping determined by flow cytometry. Genetic characterization includes HLA class I alleles (A, B and C) and four additional microsatellite markers (D6S265, D6S2222, D6S105 and D6S2239) spanning 5 Megabases in the 6p21.3 region. RESULTS: Eighty-two extended C282Y carrying haplotypes were defined. Single-locus analysis revealed that the HLA-A region was associated with CD8+ T-cell numbers. Multivariate analysis showed that the combinations of the most common HLA-A alleles (HLA-A*03, -A*02 and -A*01) were associated with significantly lower numbers of CD8+ T-lymphocytes (0.30 ± 0.14 × 10(6)/ml), in comparison with subjects carrying only one copy of those alleles (0.46 ± 0.19 × 10(6)/ml) and subjects without any copy of those alleles (0.79 ± 0.15 × 10(6)/ml;p = 0.0001). No differences were observed in CD8+ T-cell counts among control subjects carrying the same combinations of HLA-A alleles (0.47 ± 0.14; 0.45 ± 0.21 and 0.41 ± 0.17 × 10(6)/ml, respectively), therefore not supporting a direct effect of HLA specificity but rather an indirect association with a locus close to HLA-A. Multivariate analysis showed that the combination of the most common HLA-A alleles also have an impact on the clinical expression of HH in terms of iron stores, in males(p = 0.0009). CONCLUSION: The present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH). It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed

Chronic Losartan Administration Reduces Mortality and Preserves Cardiac but Not Skeletal Muscle Function in Dystrophic Mice

Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6–9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease

Early detection of breast, cervical, ovarian and endometrial cancers in low resource countries: an integrated approach

The incidence of breast and gynecological cancers continues to increase in low and middle resource countries [LRC'S and MRC's] with a disproportionately higher mortality rate compared to that in high resource countries. This has been attributed to factors such as an increased life span due to better control of communicable diseases and improved nutrition, as well as lifestyle and reproductive changes. A lack of public awareness and understanding of these cancers, absence of an organized screening program and a lack of accessible and effective treatment options, is responsible for the higher mortality rate. A practical approach of a combined program of integrating a well woman examination with screening for breast and cervical cancer and diagnostic evaluation for Ovarian and Endometrial cancer in symptomatic women is proposed in this article which can serve as a model to be studied for efficacy in low resource countries

The role of rock joint frictional strength in the containment of fracture propagation

The fracturing phenomenon within the reservoir environment is a complex process that is controlled by several factors and may occur either naturally or by artificial drivers. Even when deliberately induced, the fracturing behaviour is greatly influenced by the subsurface architecture and existing features. The presence of discontinuities such as joints, artificial and naturally occurring faults and interfaces between rock layers and microfractures plays an important role in the fracturing process and has been known to significantly alter the course of fracture growth. In this paper, an important property (joint friction) that governs the shear behaviour of discontinuities is considered. The applied numerical procedure entails the implementation of the discrete element method to enable a more dynamic monitoring of the fracturing process, where the joint frictional property is considered in isolation. Whereas fracture propagation is constrained by joints of low frictional resistance, in non-frictional joints, the unrestricted sliding of the joint plane increases the tendency for reinitiation and proliferation of fractures at other locations. The ability of a frictional joint to suppress fracture growth decreases as the frictional resistance increases; however, this phenomenon exacerbates the influence of other factors including in situ stresses and overburden conditions. The effect of the joint frictional property is not limited to the strength of rock formations; it also impacts on fracturing processes, which could be particularly evident in jointed rock masses or formations with prominent faults and/or discontinuities

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

A meta-analysis of long-term effects of conservation agriculture on maize grain yield under rain-fed conditions

Conservation agriculture involves reduced tillage, permanent soil cover and crop rotations to enhance soil fertility and to supply food from a dwindling land resource. Recently, conservation agriculture has been promoted in Southern Africa, mainly for maize-based farming systems. However, maize yields under rain-fed conditions are often variable. There is therefore a need to identify factors that influence crop yield under conservation agriculture and rain-fed conditions. Here, we studied maize grain yield data from experiments lasting 5 years and more under rain-fed conditions. We assessed the effect of long-term tillage and residue retention on maize grain yield under contrasting soil textures, nitrogen input and climate. Yield variability was measured by stability analysis. Our results show an increase in maize yield over time with conservation agriculture practices that include rotation and high input use in low rainfall areas. But we observed no difference in system stability under those conditions. We observed a strong relationship between maize grain yield and annual rainfall. Our meta-analysis gave the following findings: (1) 92% of the data show that mulch cover in high rainfall areas leads to lower yields due to waterlogging; (2) 85% of data show that soil texture is important in the temporal development of conservation agriculture effects, improved yields are likely on well-drained soils; (3) 73% of the data show that conservation agriculture practices require high inputs especially N for improved yield; (4) 63% of data show that increased yields are obtained with rotation but calculations often do not include the variations in rainfall within and between seasons; (5) 56% of the data show that reduced tillage with no mulch cover leads to lower yields in semi-arid areas; and (6) when adequate fertiliser is available, rainfall is the most important determinant of yield in southern Africa. It is clear from our results that conservation agriculture needs to be targeted and adapted to specific biophysical conditions for improved impact