Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

A pair of degenerate polymerase chain reaction (PCR) primers (LEI-1, TCG GAT CC[C,T] [G,C]TG GGT AGG GGC GT; LEI-2, ACG GAT CC[G,C] [G,C][A,C]C TAT [A,T]TT ACA CC) defining a 0.15-kb segment ofLeishmania minicircle DNA was constructed. These primers amplified not only inter- but also intraspecifically polymorphic sequences. Individual sequences revealed a higher intraspecific than interspecific divergence. It is concluded that individual sequences are of limited relevance for species determination. In contrast, when a data base of 19 different sequences was analyzed in a dendrographic plot, an accurate species differentiation was feasible

An Ultrasonic Evaluation of Damage in Cermets

Cermets are hard ceramic-metal composites with predominant ceramic phases and are finding increasing applications. It is important to understand the evolution of damage and the failure modes in these materials under dynamic loading conditions in order to design them for impact resistant applications. In this investigation a plate impact recovery technique [1,2] is used to subject cermet specimens to a single step compressive pulse of known amplitude and duration. This technique has the advantage of applying sufficiently high stress levels to initiate damage and yet providing controlled amounts of energy input to avoid catastrophic failure of the material. Ultrasonic velocity and attenuation studies are carried out on the recovered specimens to asses the evolution of damage under stress wave loading. Optical microscopy and image processing techniques are used to quantify the extent of damage in the recovered samples. Techniques such as ultrasonic measurements could prove to be useful in predicting damage levels in materials subjected to dynamic loading. The material chosen for study is a boron carbide-aluminum cermet [3].</p

Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data

Objective: To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans. Methods: We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI-visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG. Results: Seizure-onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG. Significance: Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co-located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery

Defining PD subtypes — a step toward personalized management?

A recent article published in Brain proposes a clinical method for subtyping Parkinson disease cases on an individual basis, with implications for better patient stratification for personalized medicine. The authors report biological validity in terms of imaging and cerebrospinal fluid parameters, but long-term predictive validity remains to be established.The work of the authors is supported by the NIHR Cambridge Biomedical Research Centre and the Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute

Barriers and enablers to the implementation of the 6-PACK falls prevention program: A preimplementation study in hospitals participating in a cluster randomised controlled trial

Evidence for effective falls prevention interventions in acute wards is limited. One reason for this may be suboptimal program implementation. This study aimed to identify perceived barriers and enablers of the implementation of the 6-PACK falls prevention program to inform the implementation in a randomised controlled trial. Strategies to optimise successful implementation of 6-PACK were also sought. A mixed-methods approach was applied in 24 acute wards from 6 Australian hospitals. Participants were nurses working on participating wards and senior hospital staff including Nurse Unit Managers; senior physicians; Directors of Nursing; and senior personnel involved in quality and safety or falls prevention. Information on barriers and enablers of 6-PACK implementation was obtained through surveys, focus groups and interviews. Questions reflected the COM-B framework that includes three behaviour change constructs of: capability, opportunity and motivation. Focus group and interview data were analysed thematically, and survey data descriptively. The survey response rate was 60% (420/702), and 12 focus groups (n = 96 nurses) and 24 interviews with senior staff were conducted. Capability barriers included beliefs that falls could not be prevented; and limited knowledge on falls prevention in patients with complex care needs (e.g. cognitive impairment). Capability enablers included education and training, particularly face to face case study based approaches. Lack of resources was identified as an opportunity barrier. Leadership, champions and using data to drive practice change were recognised as opportunity enablers. Motivation barriers included complacency and lack of ownership in falls prevention efforts. Motivation enablers included senior staff articulating clear goals and a commitment to falls prevention; and use of reminders, audits and feedback. The information gained from this study suggests that regular practical face-to-face education and training for nurses; provision of equipment; audit, reminders and feedback; leadership and champions; and the provision of falls data is key to successful falls prevention program implementation in acute hospitals

Three applications of path integrals: equilibrium and kinetic isotope effects, and the temperature dependence of the rate constant of the [1,5] sigmatropic hydrogen shift in (Z)-1,3-pentadiene

Recent experiments have confirmed the importance of nuclear quantum effects even in large biomolecules at physiological temperature. Here we describe how the path integral formalism can be used to describe rigorously the nuclear quantum effects on equilibrium and kinetic properties of molecules. Specifically, we explain how path integrals can be employed to evaluate the equilibrium (EIE) and kinetic (KIE) isotope effects, and the temperature dependence of the rate constant. The methodology is applied to the [1,5] sigmatropic hydrogen shift in pentadiene. Both the KIE and the temperature dependence of the rate constant confirm the importance of tunneling and other nuclear quantum effects as well as of the anharmonicity of the potential energy surface. Moreover, previous results on the KIE were improved by using a combination of a high level electronic structure calculation within the harmonic approximation with a path integral anharmonicity correction using a lower level method.Comment: 9 pages, 4 figure

Transcriptomic profiling reveals a pronociceptive role for angiotensin II in inflammatory bowel disease.

Visceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics often lack efficacy or have intolerable side effects, driving the need for a more complete understanding of the mechanisms causing pain. Whole transcriptome gene expression analysis was performed by bulk RNA sequencing of colonic biopsies from patients with ulcerative colitis (UC) and Crohn's disease (CD) reporting abdominal pain and compared with noninflamed control biopsies. Potential pronociceptive mediators were identified based on gene upregulation in IBD biopsy tissue and cognate receptor expression in murine colonic sensory neurons. Pronociceptive activity of identified mediators was assessed in assays of sensory neuron and colonic afferent activity. RNA sequencing analysis highlighted a 7.6-fold increase in the expression of angiotensinogen transcripts, Agt , which encode the precursor to angiotensin II (Ang II), in samples from UC patients ( P = 3.2 × 10 -8 ). Consistent with the marked expression of the angiotensin AT 1 receptor in colonic sensory neurons, Ang II elicited an increase in intracellular Ca 2+ in capsaicin-sensitive, voltage-gated sodium channel subtype Na V 1.8-positive sensory neurons. Ang II also evoked action potential discharge in high-threshold colonic nociceptors. These effects were inhibited by the AT 1 receptor antagonist valsartan. Findings from our study identify AT 1 receptor-mediated colonic nociceptor activation as a novel pathway of visceral nociception in patients with UC. This work highlights the potential utility of angiotensin receptor blockers, such as valsartan, as treatments for pain in IBD

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study

Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org