To compare two molecular assays (rrs quantitative PCR (qPCR) versus a combined 16SrRNA and LipL32 qPCR) on different sample types for diagnosing leptospirosis in febrile patients presenting to ...Mahosot Hospital, Vientiane, Laos.
Serum, buffy coat and urine samples were collected on admission, and follow-up serum ∼10 days later. Leptospira spp. culture and microscopic agglutination tests (MAT) were performed as reference standards. Bayesian latent class modelling was performed to estimate sensitivity and specificity of each diagnostic test.
In all, 787 patients were included in the analysis: 4/787 (0.5%) were Leptospira culture positive, 30/787 (3.8%) were MAT positive, 76/787 (9.7%) were rrs qPCR positive and 20/787 (2.5%) were 16SrRNA/LipL32 qPCR positive for pathogenic Leptospira spp. in at least one sample. Estimated sensitivity and specificity (with 95% CI) of 16SrRNA/LipL32 qPCR on serum (53.9% (33.3%–81.8%); 99.6% (99.2%–100%)), buffy coat (58.8% (34.4%–90.9%); 99.9% (99.6%–100%)) and urine samples (45.0% (27.0%–66.7%); 99.6% (99.3%–100%)) were comparable with those of rrs qPCR, except specificity of 16SrRNA/LipL32 qPCR on urine samples was significantly higher (99.6% (99.3%–100%) vs. 92.5% (92.3%–92.8%), p <0.001). Sensitivities of MAT (16% (95% CI 6.3%–29.4%)) and culture (25% (95% CI 13.3%–44.4%)) were low. Mean positive Cq values showed that buffy coat samples were more frequently inhibitory to qPCR than either serum or urine (p <0.001).
Serum and urine are better samples for qPCR than buffy coat, and 16SrRNA/LipL32 qPCR performs better than rrs qPCR on urine. Quantitative PCR on admission is a reliable rapid diagnostic tool, performing better than MAT or culture, with significant implications for clinical and epidemiological investigations of this global neglected disease.
Background and objective
Previous research suggests that measures of cognitive process may be confounded by the inclusion of items that also assess cognitive content. The primary aims of this content ...review were to: (1) identify the domains of cognitive processes assessed by measures used in pain research; and (2) determine if pain‐specific cognitive process measures with adequate psychometric properties exist.
Databases and data treatment
PsychInfo, CINAHL, PsycArticles, MEDLINE, and Academic Search Complete databases were searched to identify the measures of cognitive process used in pain research. Identified measures were double coded and the measure's items were rated as: (1) cognitive content; (2) cognitive process; (3) behavioural/social; and/or (4) emotional coping/responses to pain.
Results
A total of 319 scales were identified; of these, 29 were coded as providing an un‐confounded assessment of cognitive process, and 12 were pain‐specific. The cognitive process domains assessed in these measures are Absorption, Dissociation, Reappraisal, Distraction/Suppression, Acceptance, Rumination, Non‐Judgment, and Enhancement. Pain‐specific, un‐confounded measures were identified for: Dissociation, Reappraisal, Distraction/Suppression, and Acceptance. Psychometric properties of all 319 scales are reported in supplementary material.
Conclusions
To understand the importance of cognitive processes in influencing pain outcomes as well as explaining the efficacy of pain treatments, valid and pain‐specific cognitive process measures that are not confounded with non‐process domains (e.g., cognitive content) are needed. The findings of this content review suggest that future research focused on developing cognitive process measures is critical in order to advance our understanding of the mechanisms that underlie effective pain treatment.
Significance
Many cognitive process measures used in pain research contain a ‘mix’ of items that assess cognitive process, cognitive content, and behavioural/emotional responses. Databases searched: PsychInfo, CINAHL, PsycArticles, MEDLINE and Academic Search Complete. This review describes the domains assessed by measures assessing cognitive processes in pain research, as well as the strengths and limitations of these measures.
The main objective of this investigation is to develop a chronotherapeutic drug delivery of various natural polymers based colon targeted drug delivery systems to treat early morning sign in BP. The ...polymers such as Tamarind gum, Okra gum and Chitosan were used in the formulation design. A model drug Propranolol HCl was incorporated in the formulation in order to assess the controlled release and time dependent release potential of various natural polymers. A novel polymer Tamarind gum was extracted and used as a prime polymer in this study to prove the superiority of this polymer over other leading natural polymer. Propranolol HCl was used as a model drug which undergoes hepatic metabolism and witnesses the poor bioavailability. The matrix tablets of Propranolol HCl were prepared by direct compression. The tablets were evaluated for various quality control parameters and found to be within the limits. Carbopol 940 was used as an auxiliary polymer to modify the drug release and physicochemical characteristics of the tablets. The in vitro release studies were performed in 0.1N HCl for 1.5h, followed by pH 6.8 phosphate buffer for 2h and pH 7.4 phosphate buffer till maximum amount of drug release. The in vitro release profile of the formulations were fitted with various pharmacokinetic mathematical models and analyzed for release profile. The formulations prepared with Tamarind gum prolonged the release for an extended period of time compared to other polymer based formulation and showed an excellent compression characteristic.
Finding optimal Golomb rulers is an extremely challenging combinatorial problem. The distance between each pair of mark is unique in a Golomb ruler. For a given number of marks, an optimal Golomb ...ruler has the minimum length. Golomb rulers are used in application areas such as X-ray crystallography, radio astronomy, information theory, and pulse phase modulation. The most recent optimal Golomb ruler search algorithm hybridises a range of techniques such as greedy randomised adaptive search, scatter search, tabu search, clustering techniques, and constraint programming, and obtains optimal Golomb rulers of up to 16 marks with very low success rates. In this paper, we provide tight upper bounds for Golomb ruler marks and present heuristic-based effective domain reduction techniques. Using these along with tabu and configuration checking meta-heuristics, we then develop a constraint-based multi-point local search algorithm to perform a satisfaction search for optimal Golomb rulers of specified length. We then present an algorithm to perform an optimisation search that minimises the length using the satisfaction search repeatedly. Our satisfaction search finds optimal Golomb rulers of up to 19 marks while the optimisation search finds up to 17 marks.
Summary
Objective To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia.
Design Cross‐sectional survey.
Setting Pharmacies and shops selling antimalarial drugs in ...Myanmar (Burma), Lao PDR, Vietnam, Cambodia and Thailand.
Main outcome measures Proportion of artemisinin derivatives or mefloquine containing drugs of substandard quality.
Results Of the 188 tablet packs purchased which were labelled as ‘artesunate’ 53% did not contain any artesunate. All counterfeit artesunate tablets were labelled as manufactured by ‘Guilin Pharma’, and refinements of the fake blisterpacks made them often hard to distinguish from their genuine counterparts. No other artemisinin derivatives were found to be counterfeited. Of the 44 mefloquine samples, 9% contained <10% of the expected amount of active ingredient.
Conclusions An alarmingly high proportion of antimalarial drugs bought in pharmacies and shops in mainland SE Asia are counterfeit, and the problem has increased significantly compared with our previous survey in 1999–2000. This is a serious threat to public health in the region.
Modern agriculture and conventional breeding and the liberal use of high inputs has resulted in the loss of genetic diversity and the stagnation of yields in cereals in less favourable areas. ...Increasingly landraces are being replaced by modern cultivars which are less resilient to pests, diseases and abiotic stresses and thereby losing a valuable source of germplasm for meeting the future needs of sustainable agriculture in the context of climate change. Where landraces persist there is concern that their potential is not fully realised. Much effort has gone into collecting, organising, studying and analysing landraces recently and we review the current status and potential for their improved deployment and exploitation, and incorporation of their positive qualities into new cultivars or populations for more sustainable agricultural production. In particular their potential as sources of novel disease and abiotic stress resistance genes or combination of genes if deployed appropriately, of phytonutrients accompanied with optimal micronutrient concentrations which can help alleviate aging-related and chronic diseases, and of nutrient use efficiency traits.We discuss the place of landraces in the origin of modern cereal crops and breeding of elite cereal cultivars, the importance of on-farm and ex situ diversity conservation; how modern genotyping approaches can help both conservation and exploitation; the importance of different phenotyping approaches; and whether legal issues associated with landrace marketing and utilisation need addressing. In this review of the current status and prospects for landraces of cereals in the context of sustainable agriculture, the major points are the following: (1) Landraces have very rich and complex ancestry representing variation in response to many diverse stresses and are vast resources for the development of future crops deriving many sustainable traits from their heritage. (2) There are many germplasm collections of landraces of the major cereals worldwide exhibiting much variation in valuable morphological, agronomic and biochemical traits. The germplasm has been characterised to variable degrees and in many different ways including molecular markers which can assist selection. (3) Much of this germplasm is being maintained both in long-term storage and on farm where it continues to evolve, both of which have their merits and problems. There is much concern about loss of variation, identification, description and accessibility of accessions despite international strategies for addressing these issues. (4) Developments in genotyping technologies are making the variation available in landraces ever more accessible. However, high quality, extensive and detailed, relevant and appropriate phenotyping needs to be associated with the genotyping to enable it to be exploited successfully. We also need to understand the complexity of the genetics of these desirable traits in order to develop new germplasm. (5) Nutrient use efficiency is a very important criterion for sustainability. Landrace material offers a potential source for crop improvement although these traits are highly interactive with their environment, particularly developmental stage, soil conditions and other organisms affecting roots and their environment. (6) Landraces are also a potential source of traits for improved nutrition of cereal crops, particularly antioxidants, phenolics in general, carotenoids and tocol in particular. They also have the potential to improve mineral content, particularly iron and zinc, if these traits can be successfully transferred to improved varieties. (7) Landraces have been shown to be valuable sources of resistance to pathogens and there is more to be gained from such sources. There is also potential, largely unrealised, for disease tolerance and resistance or tolerance of pest and various abiotic stresses too including to toxic environments. (8) Single gene traits are generally easily transferred from landrace germplasm to modern cultivars, but most of the desirable traits characteristic of landraces are complex and difficult to express in different genetic backgrounds. Maintaining these characteristics in heterogeneous landraces is also problematic. Breeding, selection and deployment methods appropriate to these objectives should be used rather than those used for high input intensive agriculture plant breeding. (9) Participatory plant breeding and variety selection has proven more successful than the approach used in high input breeding programmes for landrace improvement in stress-prone environments where sustainable approaches are a high priority. Despite being more complex to carry out, it not only delivers improved germplasm, but also aids uptake and communication between farmers, researchers and advisors for the benefit of all. (10) Previous seed trade legislation was designed primarily to protect trade and return royalty income to modern plant breeders with expensive programmes to fund. As the desirability of using landraces becomes more apparent to achieve greater sustainability, legislation changes are being made to facilitate this trade too. However, more changes are needed to promote the exploitation of diversity in landraces and encourage their use.
Protein contact maps capture coevolutionary interactions between amino acid residue pairs that are spatially within certain proximity threshold. Predicted contact maps are used in many protein ...related problems that include drug design, protein design, protein function prediction, and protein structure prediction. Contact map prediction has achieved significant progress lately but still further challenges remain with prediction of contacts between residues that are separated in the amino acid residue sequence by large numbers of other residues. In this paper, with experimental results on 5 standard benchmark datasets that include membrane proteins, we show that contact map prediction could be significantly enhanced by using ensembles of various state-of-the-art short distance predictors and then by converting predicted distances into contact probabilities. Our program along with its data is available from https://gitlab.com/mahnewton/ecp.
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•Enhanced contact maps from average contact probabilities obtained from inter-residue distances predicted by recent methods.•Protein 3D Structure Construction: More accurate 3D protein structures are constructed by using the predicted enhanced contact maps.•The program for the proposed ensemble-based protein contact map predictor is available from https://gitlab.com/mahnewton/ecp.
Protein structure prediction (PSP) is a crucial issue in Bioinformatics. PSP has its important use in many vital research areas that include drug discovery. One of the important intermediate steps in ...PSP is predicting a protein’s beta-sheet structures. Because of non-local interactions among numerous irregular areas in beta-sheets, their highly accurate prediction is challenging. The challenge is compounded when a given protein’s structure has a large number of beta-sheets. In this paper, we specifically refine the beta-sheets of a protein structure by using a local search method. Then, we use another local search method to refine the full structure. Our search methods analyse residue–residue distance-based scores and apply geometric restrictions gained from deep learning models. Moreover, our search methods recognise the regions of the current conformations prompting the nether scores and generate neighbouring conformations focusing on that identified regions and making alterations there. On a set of standard 88 proteins of various sizes between 46 and 450 residues, our method successfully outperforms state-of-the-art PSP search algorithms. The improvements are more than 12% in average root mean squared distance (RMSD), template modelling score (TM-score), and global distance test (GDT) values.
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The fungal microbiome, or mycobiome, is a poorly described component of the gut ecosystem and little is known about its structure and development in children. In South Africa, there have been no ...culture-independent evaluations of the child gut mycobiota. This study aimed to characterise the gut mycobiota and explore the relationships between fungi and bacteria in the gut microbiome of children from Cape Town communities.
Stool samples were collected from children enrolled in the TB-CHAMP clinical trial. Internal transcribed spacer 1 (ITS1) gene sequencing was performed on a total of 115 stool samples using the Illumina MiSeq platform. Differences in fungal diversity and composition in relation to demographic, clinical, and environmental factors were investigated, and correlations between fungi and previously described bacterial populations in the same samples were described.
Taxa from the genera Candida and Saccharomyces were detected in all participants. Differential abundance analysis showed that Candida spp. were significantly more abundant in children younger than 2 years compared to older children. The gut mycobiota was less diverse than the bacterial microbiota of the same participants, consistent with the findings of other human microbiome studies. The variation in richness and evenness of fungi was substantial, even between individuals of the same age. There was significant association between vitamin A supplementation and higher fungal alpha diversity (p = 0.047), and girls were shown to have lower fungal alpha diversity (p = 0.003). Co-occurrence between several bacterial taxa and Candida albicans was observed.
The dominant fungal taxa in our study population were similar to those reported in other paediatric studies; however, it remains difficult to identify the true core gut mycobiota due to the challenges set by the low abundance of gut fungi and the lack of true gut colonising species. The connection between the microbiota, vitamin A supplementation, and growth and immunity warrants exploration, especially in populations at risk for micronutrient deficiencies. While we were able to provide insight into the gut mycobiota of young South African children, further functional studies are necessary to explain the role of the mycobiota and the correlations between bacteria and fungi in human health.
Predicted inter-residue distances are a key behind recent success in high quality protein structure prediction (PSP). However, prediction of both short and long distance values together is ...challenging. Consequently, predicted short distances are mostly used by existing PSP methods. In this paper, we use a stacked meta-ensemble method to combine deep learning models trained for different ranges of real-valued distances. On five benchmark sets of proteins, our proposed inter-residue distance prediction method improves mean Local Distance Different Test (LDDT) scores at least by 5% over existing such methods. Moreover, using a real-valued distance based conformational search algorithm, we also show that predicted long distances help obtain significantly better protein conformations than when only predicted short distances are used. Our method is named meta-ensemble for distance prediction (MDP) and its program is available from https://gitlab.com/mahnewton/mdp.
•A stacked meta-ensemble method to predict protein inter-residue long-range real-valued distances.•Improved Cβ−Cβ, Cα−Cα and N–O long-range real-valued distance prediction.•Improved protein 3D structure construction using long-range predicted distances.•The distance predictor’s program is available from https://gitlab.com/mahnewton/mdp.
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