3,048 research outputs found
The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes
To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance
T Wave Alternans in high arrhythmic risk patients: Analysis in time and frequency domains: A pilot study
BACKGROUND: T wave alternans (TA) is a repolarisation phenomenon manifesting as a microvolt beat to beat change in the amplitude of the T wave and ST segment. TA has been shown to be a predictor of arrhythmic risk in unselected myocardial infarction populations. TA has not been used to differentiate risk within the ischaemic cardiomyopathy population. METHODS: The subjects investigated comprised, Group 1: 7 stable patients with remote (>20 months) extensive myocardial scarring and no arrhythmic events (NYHA 3 and 4). Group2: 9 post infarction patients with malignant arrhythmia and implantable defibrillator. During breath holding, 20 continuous QRST complexes from each patients X, Y and Z leads were digitally recorded. Time domain, resultant absolute difference vectors (ATA), were calculated for alternate resultant T wave sequences. Group differences between the magnitude and temporal distribution of mean ATAs and their spectral and cross-spectral analysis were compared. RESULTS: Group 1 v Group 2 mean ATAs were 10.7 (7.17) v 11.7 (8.48) respectively, not significant. Each group had a homogenous temporal distribution of ATAs. Both group's largest mean ATA frequency components were between 0 to 25 Hz, the largest ATA component being at the DC frequency. Cross spectral analysis showed no significant differences in group ATA frequency content. CONCLUSION: The frequency content and microvolt magnitude of T wave alternans was not significantly different in these two groups. The specificity of T wave alternans for differentiating arrhythmic risk in post infarction scarring and heart failure needs investigation
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Symptoms predicting psychosocial impairment in bulimia nervosa
Purpose
The current study aimed to determine which particular eating disorder (ED) symptoms and related features, such as BMI and psychological distress, uniquely predict impairment in bulimia nervosa (BN).
Methods
Two hundred and twenty-two adults with BN completed questionnaires assessing ED symptoms, general psychological distress, and psychosocial impairment. Regression analyses were used to determine predictors which account for variance in impairment.
Results
Four variables emerged as significant predictors of psychosocial impairment: concerns with eating; concerns with weight and shape; dietary restraint; and general psychological distress.
Conclusions
Findings support previous work highlighting the importance of weight and shape concerns in determining ED-related impairment. Other ED symptoms, notably dietary restraint and concerns with eating, were also significant predictors as was psychological distress. Results suggest that cognitive aspects of EDs, in addition to psychological distress, may be more important determinants of impairment than behavioural symptoms, such as binge eating or purging
Warped Riemannian metrics for location-scale models
The present paper shows that warped Riemannian metrics, a class of Riemannian
metrics which play a prominent role in Riemannian geometry, are also of
fundamental importance in information geometry. Precisely, the paper features a
new theorem, which states that the Rao-Fisher information metric of any
location-scale model, defined on a Riemannian manifold, is a warped Riemannian
metric, whenever this model is invariant under the action of some Lie group.
This theorem is a valuable tool in finding the expression of the Rao-Fisher
information metric of location-scale models defined on high-dimensional
Riemannian manifolds. Indeed, a warped Riemannian metric is fully determined by
only two functions of a single variable, irrespective of the dimension of the
underlying Riemannian manifold. Starting from this theorem, several original
contributions are made. The expression of the Rao-Fisher information metric of
the Riemannian Gaussian model is provided, for the first time in the
literature. A generalised definition of the Mahalanobis distance is introduced,
which is applicable to any location-scale model defined on a Riemannian
manifold. The solution of the geodesic equation is obtained, for any Rao-Fisher
information metric defined in terms of warped Riemannian metrics. Finally,
using a mixture of analytical and numerical computations, it is shown that the
parameter space of the von Mises-Fisher model of -dimensional directional
data, when equipped with its Rao-Fisher information metric, becomes a Hadamard
manifold, a simply-connected complete Riemannian manifold of negative sectional
curvature, for . Hopefully, in upcoming work, this will be
proved for any value of .Comment: first version, before submissio
Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer
Stochastic population growth in spatially heterogeneous environments
Classical ecological theory predicts that environmental stochasticity
increases extinction risk by reducing the average per-capita growth rate of
populations. To understand the interactive effects of environmental
stochasticity, spatial heterogeneity, and dispersal on population growth, we
study the following model for population abundances in patches: the
conditional law of given is such that when is small the
conditional mean of is approximately , where and are the abundance and per
capita growth rate in the -th patch respectivly, and is the
dispersal rate from the -th to the -th patch, and the conditional
covariance of and is approximately . We show for such a spatially extended population that if
is the total population abundance, then ,
the vector of patch proportions, converges in law to a random vector
as , and the stochastic growth rate equals the space-time average per-capita growth rate
\sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the
space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i
Y_\infty^j] experienced by the population. We derive analytic results for the
law of , find which choice of the dispersal mechanism produces an
optimal stochastic growth rate for a freely dispersing population, and
investigate the effect on the stochastic growth rate of constraints on
dispersal rates. Our results provide fundamental insights into "ideal free"
movement in the face of uncertainty, the persistence of coupled sink
populations, the evolution of dispersal rates, and the single large or several
small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure
Ultrasound findings and histological features of ductal carcinoma in situ detected by ultrasound examination alone
The Role of RANK-Ligand Inhibition in Cancer: The Story of Denosumab
The bone is a very common site of metastasis in patients with advanced cancer. Skeletal metastases are most common in breast and prostate cancer, but virtually any advanced cancer may disseminate to the bone. On the basis of recent advances in the understanding of bone remodeling processes, denosumab, a fully human monoclonal antibody against RANK-L, has been developed. Phase III clinical trials have demonstrated that denosumab is well tolerated and effective in the treatment of bone loss and prevention of skeletal-related events in patients with bone metastases
Control of magnetic anisotropy by orbital hybridization in (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattice
The asymmetry of chemical nature at the hetero-structural interface offers an
unique opportunity to design desirable electronic structure by controlling
charge transfer and orbital hybridization across the interface. However, the
control of hetero-interface remains a daunting task. Here, we report the
modulation of interfacial coupling of (La0.67Sr0.33MnO3)n/(SrTiO3)n
superlattices by manipulating the periodic thickness with n unit cells of
SrTiO3 and n unit cells La0.67Sr0.33MnO3. The easy axis of magnetic anisotropy
rotates from in-plane (n = 10) to out-of-plane (n = 2) orientation at 150 K.
Transmission electron microscopy reveals enlarged tetragonal ratio > 1 with
breaking of volume conservation around the (La0.67Sr0.33MnO3)n/(SrTiO3)n
interface, and electronic charge transfer from Mn to Ti 3d orbitals across the
interface. Orbital hybridization accompanying the charge transfer results in
preferred occupancy of 3d3z2-r2 orbital at the interface, which induces a
stronger electronic hopping integral along the out-of-plane direction and
corresponding out-of-plane magnetic easy axis for n = 2. We demonstrate that
interfacial orbital hybridization in superlattices of strongly correlated
oxides may be a promising approach to tailor electronic and magnetic properties
in device applications
HTLV-1-Associated Adult T Cell Leukemia Lymphoma Presenting as Granulomatous Pneumocystis Jiroveci Pneumonia (PJP) and Hypercalcemia
BACKGROUND: Since the initial description of human T cell lymphotropic virus (HTLV-1), clusters of this infection have been detected globally. Unlike HIV infection, most patients infected with HTLV-1 remain asymptomatic throughout their lifetime. CASE REPORT: We report the case of a 39-year-old Afro-Caribbean man with HTLV-1 infection presenting as hypercalcemia and granulomatous pneumocystis jiroveci pneumonia. RESULTS: Interestingly, the hypercalcemia presented with normal parathyroid hormone–related protein and low 1,25 dihydroxyvitamin D levels, and the presence of pneumocystis jiroveci in the granulomas was diagnosed with transbronchial biopsy taken during bronchoscopy. HTLV-1-associated adult T cell leukemia lymphoma (ATLL) was diagnosed in this patient by bone marrow and lymph node biopsy. CONCLUSION: Increased bone resorption, likely cytokine-mediated, is the most likely mechanism of hypercalcemia in this patient. This is believed to be the first description of this type of reaction to pneumocystis jiroveci in a HTLV-1-infected ATLL patient
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