906 research outputs found
Railway subgrade performance after repeated flooding ā Large-scale laboratory testing
A rail track system comprises a number of components and, in order to analyse and predict track behaviour, it is essential to understand the function of each component as each will have a major influence on overall track performance. Historically, rail track substructure, particularly the subgrade, has been given less attention than the superstructure despite its importance in track design. This paper presents a full-scale experimental investigation to study the behaviour of subgrade in both saturated and unsaturated conditions, and how this behaviour changes with soil suction. Further, the investigation also studies the role of sand-blanketing during and after repeated flooding events. The results show that as soil suction reduces, flooding results in a continual reduction in both soil stiffness and track stiffness. It is also shown that the introduction of a sand-blanket has limited effectiveness as a drainage material, particularly after prolonged and repeated flooding
UÄinak atorvastatina na debljinu arterijske intime medije u bolesnika s ishemijskim moždanim udarom
Occlusion of the initial segment of internal carotid artery is the most common reason for vascular events in the brain. The purpose of this study was to investigate the effect of oneyear treatment with atorvastatin on intima-media thickness (IMT) of carotid arteries as a measure of atherosclerosis in stroke patients. In this prospective interventional study, 44 patients with ischemic stroke were investigated. Patients were treated with atorvastatin 40 mg once a day for one year. IMT of carotid arteries was measured by extracranial Doppler ultrasonography in the distal part of the common carotid artery at the beginning of the study, at 6 months and one year of treatment with atorvastatin. The IMT of both right and left carotid arteries decreased after 6- and 12-month atorvastatin treatment. Based on the results of this study, long-term administration of atorvastatin was associated
with reduction in carotid artery IMT in patients with ischemic stroke. Such a decrease in IMT may prevent subsequent stroke or cardiovascular events in these patients.Blokada poÄetnog dijela interne karotidne arterije najÄeÅ”Äi je razlog vaskularnih ispada u mozgu. Namjera ovoga istraživanja bila je ispitati uÄinak jednogodiÅ”nje terapije atorvastatinom na debljinu intime medije (intima-media thickness, IMT) karotidnih arterija kao mjere ateroskleroze kod bolesnika s moždanim udarom. U ovoj prospektivnoj intervencijskoj studiji ispitana su 44 bolesnika s ishemijskim moždanim udarom. Bolesnici su lijeÄeni atorvastatinom, 40 mg jedanput na dan kroz jednu godinu. IMT karotidnih arterija mjeren je ekstrakranijskom Doppler ultrasonografijom u distalnom dijelu zajedniÄke karotidne arterije na poÄetku istraživanja te nakon 6 mjeseci i 12 mjeseci lijeÄenja atorvastatinom. Zabilježeno je sniženje IMT i u desnoj i u lijevoj karotidnoj arteriji nakon 6 mjeseci i 12 mjeseci lijeÄenja atorvastatinom. Rezultati ovoga istraživanja pokazuju da je dugotrajno uzimanje atorvastatina bilo udruženo sa smanjenjem IMT karotidnih arterija u bolesnika s ishemijskim moždanim udarom. Takvo sniženje IMT moglo bi sprijeÄiti naknadni moždani udar ili kardiovaskularne ispade kod ovih bolesnika
Membranous nephropathy: a retrospective observational study of membranous nephropathy in north east and central London
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Work on this study was supported in part by grants from the European Union, FP7 (EURenOmics grant agreement 2012-305608)
Extraluminal Amyloidoma of the Pelvic Cavity Causing Large Bowel Obstruction
Amyloidosis is a group of diverse disorders that fall into several major categories: primary, secondary, dialysis-associated, and hereditary forms. Clinically, amyloidosis may be categorized as localized or systemic. The gastrointestinal tract is among the most common places for deposition of amyloid, but large, localized amyloid deposits are an uncommon occurrence and rarely cause extraluminal bowel compression resulting in obstruction as was seen in the case presented in this clinical scenario
Evaluation of the impact of a school gardening intervention on children's fruit and vegetable intake: a randomised controlled trial.
Background: Current academic literature suggests that school gardening programmes can provide an interactive environment with the potential to change childrenās fruit and vegetable intake. This is the first cluster randomised controlled trial (RCT) designed to evaluate whether a school gardening programme can have an effect on childrenās fruit and vegetable intake.
Methods: The trial included children from 23 schools; these schools were randomised into two groups, one to receive the Royal Horticultural Society (RHS)-led intervention and the other to receive the less involved Teacher-led intervention. A 24-hour food diary (CADET) was used to collect baseline and follow-up dietary intake 18 months apart. Questionnaires were also administered to evaluate the intervention implementation.
Results: A total of 641 children completed the trial with a mean age of 8.1 years (95% CI: 8.0, 8.4). The unadjusted results from multilevel regression analysis revealed that for combined daily fruit and vegetable intake the Teacher-led group had a higher daily mean change of 8 g (95% CI: ā19, 36) compared to the RHS-led group -32 g (95% CI: ā60, ā3). However, after adjusting for possible confounders this difference was not significant (intervention effect: ā40 g, 95% CI: ā88, 1; pā=ā0.06). The adjusted analysis of process measures identified that if schools improved their gardening score by 3 levels (a measure of school gardening involvement - the scale has 6 levels from 0 āno gardenā to 5 ācommunity involvementā), irrespective of group allocation, children had, on average, a daily increase of 81 g of fruit and vegetable intake (95% CI: 0, 163; pā=ā0.05) compared to schools that had no change in gardening score.
Conclusions: This study is the first cluster randomised controlled trial designed to evaluate a school gardening intervention. The results have found very little evidence to support the claims that school gardening alone can improve childrenās daily fruit and vegetable intake. However, when a gardening intervention is implemented at a high level within the school it may improve childrenās daily fruit and vegetable intake by a portion. Improving childrenās fruit and vegetable intake remains a challenging task
Should mechanical dyssynchrony be assessed in patients with implantable cardioverter-defibrillators?
Cardiac Dysfunction and Arrhythmia
Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.
The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts
Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude
Background: This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings: Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.8061.00 mm; mean change695%CI). This change was inverted towards the inner four subfields (TRT inner = 21.8960.97 mm) with significant reduction of TRT in the fovea (TRT foveal = 26.6260.90 mm) at altitude. BCVA revealed no significant difference compared to baseline (0.0660.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = 21.1260.68 dB). At baseline recordings before and.2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance: During acute exposure to high altitude central retinal thickness is subject to minor, ye
First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal
BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg
Immune-Mobilizing Monoclonal T Cell Receptors Mediate Specific and Rapid Elimination of Hepatitis B-Infected Cells
Background and Aims:
Therapies for chronic hepatitis B virus (HBV) infection are urgently needed because of viral integration, persistence of viral antigen expression, inadequate HBVāspecific immune responses, and treatment regimens that require lifelong adherence to suppress the virus. Immune mobilizing monoclonal T Cell receptors against virus (ImmTAV) molecules represent a therapeutic strategy combining an affinityāenhanced T Cell receptor with an antiāCD3 T Cellāactivating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virusāderived peptides presented by human leukocyte antigen (HLA).
Approach and Results:
ImmTAV molecules specific for HLAāA*02:01ārestricted epitopes from HBV envelope, polymerase, and core antigens were engineered. The ability of ImmTAVāEnv to activate and redirect polyclonal T cells toward cells containing integrated HBV and cells infected with HBV was assessed using cytokine secretion assays and imagingābased killing assays. Elimination of infected cells was further quantified using a modified fluorescent hybridization of viral RNA assay. Here, we demonstrate that picomolar concentrations of ImmTAVāEnv can redirect T cells from healthy and HBVāinfected donors toward hepatocellular carcinoma (HCC) cells containing integrated HBV DNA resulting in cytokine release, which could be suppressed by the addition of a corticosteroid in vitro. Importantly, ImmTAVāEnv redirection of T cells induced cytolysis of antigenāpositive HCC cells and cells infected with HBV in vitro, causing a reduction of hepatitis B e antigen and specific loss of cells expressing viral RNA.
Conclusions:
The ImmTAV platform has the potential to enable the elimination of infected cells by redirecting endogenous nonāHBVāspecific T cells, bypassing exhausted HBVāspecific T cells. This represents a promising therapeutic option in the treatment of chronic hepatitis B, with our lead candidate now entering trials
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