Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

On-board and Ground Visual Pose Estimation Techniques for UAV Control

In this paper, two techniques to control UAVs (Unmanned Aerial Vehicles), based on visual information are presented. The first one is based on the detection and tracking of planar structures from an on-board camera, while the second one is based on the detection and 3D reconstruction of the position of the UAV based on an external camera system. Both strategies are tested with a VTOL (Vertical take-off and landing) UAV, and results show good behavior of the visual systems (precision in the estimation and frame rate) when estimating the helicopter¿s position and using the extracted information to control the UAV

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Measured and Simulated Nitrous Oxide Emissions from Ryegrass- and Ryegrass/White Clover-Based Grasslands in a Moist Temperate Climate

There is uncertainty about the potential reduction of soil nitrous oxide (N2O) emission when fertilizer nitrogen (FN) is partially or completely replaced by biological N fixation (BNF) in temperate grassland. The objectives of this study were to 1) investigate the changes in N2O emissions when BNF is used to replace FN in permanent grassland, and 2) evaluate the applicability of the process-based model DNDC to simulate N2O emissions from Irish grasslands. Three grazing treatments were: (i) ryegrass (Lolium perenne) grasslands receiving 226 kg FN ha−1 yr−1 (GG+FN), (ii) ryegrass/white clover (Trifolium repens) grasslands receiving 58 kg FN ha−1 yr−1 (GWC+FN) applied in spring, and (iii) ryegrass/white clover grasslands receiving no FN (GWC-FN). Two background treatments, un-grazed swards with ryegrass only (G–B) or ryegrass/white clover (WC–B), did not receive slurry or FN and the herbage was harvested by mowing. There was no significant difference in annual N2O emissions between G–B (2.38±0.12 kg N ha−1 yr−1 (mean±SE)) and WC-B (2.45±0.85 kg N ha−1 yr−1), indicating that N2O emission due to BNF itself and clover residual decomposition from permanent ryegrass/clover grassland was negligible. N2O emissions were 7.82±1.67, 6.35±1.14 and 6.54±1.70 kg N ha−1 yr−1, respectively, from GG+FN, GWC+FN and GWC-FN. N2O fluxes simulated by DNDC agreed well with the measured values with significant correlation between simulated and measured daily fluxes for the three grazing treatments, but the simulation did not agree very well for the background treatments. DNDC overestimated annual emission by 61% for GG+FN, and underestimated by 45% for GWC-FN, but simulated very well for GWC+FN. Both the measured and simulated results supported that there was a clear reduction of N2O emissions when FN was replaced by BNF

A prospective, observational cohort study of patients presenting to an emergency department with acute shoulder trauma: the Manchester emergency shoulder (MESH) project

Background Fracture and dislocation of the shoulder are usually identifiable through the use of plain radiographs in an emergency department. However, other significant soft tissue injuries can be missed at initial presentation. This study used contrast enhanced magnetic resonance arthrography (MRA) to determine the pattern of underlying soft tissue injuries in patients with traumatic shoulder injury, loss of active range of motion, and normal plain radiography. Methods A prospective, observational cohort study. Twenty-six patients with acute shoulder trauma and no identifiable radiograph abnormality were screened for inclusion. Those unable to actively abduction their affected arm to 90° at initial presentation and at two week’s clinical review were consented for MRA. Results Twenty patients (Mean age 44 years, 4 females) proceeded to MRA. One patient had no abnormality, three patients showed minimal pathology. Four patients had an isolated bony/labral injury. Eight patients had injuries isolated to the rotator cuff. Four patients had a combination of bony and rotator cuff injury. Four patients were referred to a specialist shoulder surgeon following MRA and underwent surgery. Conclusions Significant soft tissue pathology was common in our cohort of patients with acute shoulder trauma, despite the reassurance of normal plain radiography. These patients were unable to actively abduct to 90° both at initial presentation and at two week’s post injury review. A more aggressive management and diagnostic strategy may identify those in need of early operative intervention and provide robust rehabilitation programmes

Mortality, Recruitment and Change of Desert Tree Populations in a Hyper-Arid Environment

BACKGROUND: Long-term vegetation changes in hyper-arid areas have long been neglected. Mortality, recruitment and change in populations of the ecologically and culturally important and drought persistent Acacia tortilis and Balanites aegyptiaca are therefore estimated in the Eastern Desert of Egypt, and are related to the primary agents of change, water conditions and human intervention. METHODOLOGY: A change analysis using high-resolution Corona images (1965) in combination with field data (2003) is the basis for recruitment, mortality and change estimates. For assessing the influence of water conditions on patterns in recruitment and survival, different types of generalized linear models are tested. CONCLUSIONS: The overall trend in population size in that part of the Eastern Desert studied here is negative. At some sites this negative trend is alarming, because the reduction in mature trees is substantial (>50%) at the same time as recruitment is nearly absent. At a few sites there is a positive trend and better recruitment. Frequent observations of sprouting in saplings indicate that this is an important mechanism to increase their persistence. It is the establishment itself that seems to be the main challenge in the recruitment process. There are indications that hydrological variables and surface water in particular can explain some of the observed pattern in mortality, but our results indicate that direct human intervention, i.e., charcoal production, is the main cause of tree mortality in the Eastern Desert

NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

UNLABELLED: β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. CONCLUSION: The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences

Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense

Control of human African sleeping sickness, caused by subspecies of the protozoan parasite Trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. To identify trypanosome proteins that have potential as biomarkers for detection and monitoring of African sleeping sickness, we have used a ‘deep-mining” proteomics approach to identify trypanosome proteins in human plasma. Abundant human plasma proteins were removed by immunodepletion. Depleted plasma samples were then digested to peptides with trypsin, fractionated by basic reversed phase and each fraction analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This sample processing and analysis method enabled identification of low levels of trypanosome proteins in pooled plasma from late stage sleeping sickness patients infected with Trypanosoma brucei rhodesiense. A total of 254 trypanosome proteins were confidently identified. Many of the parasite proteins identified were of unknown function, although metabolic enzymes, chaperones, proteases and ubiquitin-related/acting proteins were found. This approach to the identification of conserved, soluble trypanosome proteins in human plasma offers a possible route to improved disease diagnosis and monitoring, since these molecules are potential biomarkers for the development of a new generation of antigen-detection assays. The combined immuno-depletion/mass spectrometric approach can be applied to a variety of infectious diseases for unbiased biomarker identification