Electron trapping in ferroelectric HfO2

Charge trapping study at 300 and 77 K in ferroelectric (annealed Al- or Si-doped) and nonferroelectric (unannealed and/or undoped) HfO 2 films grown by atomic layer deposition reveals the presence of “deep” and “shallow” electron traps with volume concentrations in the 10 19 − cm − 3 range. The concentration of deep traps responsible for electron trapping at 300 K is virtually insensitive to the oxide doping by Al or Si but slightly decreases in films crystallized by high-temperature annealing in oxygen-free ambient. This behavior indicates that the trapping sites are intrinsic and probably related to disorder in HfO 2 rather than to the oxygen deficiency of the film. Electron injection at 77 K allowed us to fill shallow electron traps energetically distributed at ∼0.2 eV. These electrons are mobile and populate states with thermal ionization energies in the range ∼0.6–0.7 eV below the HfO 2 conduction band (CB). The trap energy depth and marginal sensitivity of their concentration to crystallization annealing or film doping with Si or Al suggests that these traps are associated with boundaries between crystalline grains and interfaces between crystalline and amorphous regions in HfO 2 films. This hypothesis is supported by density functional theory calculations of electron trapping at surfaces of monoclinic, tetragonal, and orthorhombic phases of HfO 2 . The calculated trap states are consistent with the observed thermal ionization (0.7–1.0 eV below the HfO 2 CB) and photoionization energies (in the range of 2.0–3.5 eV below the HfO 2 CB) and support their intrinsic polaronic nature

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study.

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a 'one-stop' test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants, and identify problem cases and factors that lead to discordant results. We produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams ('participants') were provided these sequence data without any other contextual information. Each participant used their choice of pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime. We found participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results, but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment, a different antibiotic would have been recommended for each isolate by at least one participant. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases, full recommendations on sequence data quality and standardization in the comparisons between genotype and resistance phenotypes will all play a fundamental role in the successful implementation of AST prediction using WGS in clinical microbiology laboratories

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

The Current Use of Drug-Eluting Balloons and Stents in Peripheral Arterial Disease: An Online Survey by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).

PURPOSE: To assess the current use of drug-eluting devices for peripheral arterial disease (PAD) among interventional radiologists following the controversy caused by the 2018 meta-analysis suggesting an increased mortality risk for paclitaxel-eluting devices. METHODS: An anonymous survey was sent to 7035 CIRSE members via email; only complete responses were included and statistically analysed. RESULTS: Three hundred and seven members (4.4%) completed the survey. Among these, 95.8% indicated that they personally perform peripheral vascular procedures. Thirty-eight percentage of respondents did not see any change of practice since 2018, while 47% reported that the use of drug-eluting devices decreased; for 13%, the use stopped altogether, while it increased in 3% of responses. 45.6% of respondents also felt the impact of the controversy in terms of pricing, availability or directives from hospital administration. A large majority of respondents (83.7%) who perform peripheral vascular procedures consider the use of these devices as safe, 12.9% were undecided and 3.4% did not consider them as safe. Among the respondents who do not perform endovascular procedures, 77% considered these devices as safe and 23% were undecided. CONCLUSION: Although the 2018 meta-analysis had a disruptive impact on the use of drug-eluting devices in PAD, with the increasing body of evidence available, a majority of respondents continue to believe in the safety of these devices for use in femoropopliteal disease

Current measures of metabolic heterogeneity within cervical cancer do not predict disease outcome

<p>Abstract</p> <p>Background</p> <p>A previous study evaluated the intra-tumoral heterogeneity observed in the uptake of F-18 fluorodeoxyglucose (FDG) in pre-treatment positron emission tomography (PET) scans of cancers of the uterine cervix as an indicator of disease outcome. This was done via a novel statistic which ostensibly measured the spatial variations in intra-tumoral metabolic activity. In this work, we argue that statistic is intrinsically <it>non</it>-spatial, and that the apparent delineation between unsuccessfully- and successfully-treated patient groups via that statistic is spurious.</p> <p>Methods</p> <p>We first offer a straightforward mathematical demonstration of our argument. Next, we recapitulate an assiduous re-analysis of the originally published data which was derived from FDG-PET imagery. Finally, we present the results of a principal component analysis of FDG-PET images similar to those previously analyzed.</p> <p>Results</p> <p>We find that the previously published measure of intra-tumoral heterogeneity is intrinsically non-spatial, and actually is only a surrogate for tumor volume. We also find that an optimized linear combination of more canonical heterogeneity quantifiers does not predict disease outcome.</p> <p>Conclusions</p> <p>Current measures of intra-tumoral metabolic activity are not predictive of disease outcome as has been claimed previously. The implications of this finding are: clinical categorization of patients based upon these statistics is invalid; more sophisticated, and perhaps innately-geometric, quantifications of metabolic activity are required for predicting disease outcome.</p

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases

Efficacy of movement control exercises versus general exercises on recurrent sub-acute nonspecific low back pain in a sub-group of patients with movement control dysfunction. protocol of a randomized controlled trial

Background: Practice guidelines recommend various types of exercise for chronic back pain but there have been few head-to-head comparisons of these interventions. General exercise seems to be an effective option for management of chronic low back pain (LBP) but very little is known about the management of a sub-acute LBP within sub-groups. Recent research has developed clinical tests to identify a subgroup of patients with chronic non-specific LBP who have movement control dysfunction (MD). Method/Design: We are conducting a randomized controlled trial (RCT) to compare the effects of general exercise and specific movement control exercise (SMCE) on disability and function in patients with MD within recurrent sub-acute LBP. The main outcome measure is the Roland Morris Disability Questionnaire. Discussion: European clinical guideline for management of chronic LBP recommends that more research is required to develop tools to improve the classification and identification of specific clinical sub-groups of chronic LBP patients. Good quality RCTs are then needed to determine the effectiveness of specific interventions aimed at these specific target groups. This RCT aims to test the hypothesis whether patients within a sub-group of MD benefit more through a specific individually tailored movement control exercise program than through general exercises

Maternal Perception of Reduced Fetal Movements Is Associated with Altered Placental Structure and Function

Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM.To determine whether maternal perception of reduced fetal movements (RFM) is associated with abnormalities in placental structure and function.Placentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function. Placentas from all pregnancies with RFM (irrespective of outcome) had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01), a higher density of syncytial knots (p<0.001) and greater proliferation index (p<0.01). Villous vascularity (p<0.001), trophoblast area (p<0.01) and system A activity (p<0.01) were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy.This study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency