13,601 research outputs found
Spectral weight transfer in a disorder-broadened Landau level
In the absence of disorder, the degeneracy of a Landau level (LL) is
, where is the magnetic field, is the area of the sample
and is the magnetic flux quantum. With disorder, localized states
appear at the top and bottom of the broadened LL, while states in the center of
the LL (the critical region) remain delocalized. This well-known phenomenology
is sufficient to explain most aspects of the Integer Quantum Hall Effect (IQHE)
[1]. One unnoticed issue is where the new states appear as the magnetic field
is increased. Here we demonstrate that they appear predominantly inside the
critical region. This leads to a certain ``spectral ordering'' of the localized
states that explains the stripes observed in measurements of the local inverse
compressibility [2-3], of two-terminal conductance [4], and of Hall and
longitudinal resistances [5] without invoking interactions as done in previous
work [6-8].Comment: 5 pages 3 figure
Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.
BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy >3 months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P <0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation
Chronic breathlessness and sleep problems: a population-based survey
ObjectivesThis study aimed to explore the relationship (presence and severity) between chronic breathlessness and sleep problems, independently of diagnoses and health service contact by surveying a large, representative sample of the general population.SettingAnalysis of the 2017 South Australian Health Omnibus Survey, an annual, cross-sectional, face-to-face, multistage, clustered area systematic sampling survey carried out in Spring 2017.Chronic breathlessness was self-reported using the ordinal modified Medical Research Council (mMRC; scores 0 (none) to 4 (housebound)) where breathlessness has been present for more than 3 of the previous 6 months. 'Sleep problems-ever' and 'sleep problem-current' were assessed dichotomously. Regression models were adjusted for age; sex and body mass index (BMI).Results2900 responses were available (mean age 48.2 years (SD=18.6); 51% were female; mean BMI 27. 1 (SD=5.9)). Prevalence was: 2.7% (n=78) sleep problems-past; 6.8% (n=198) sleep problems-current and breathlessness (mMRC 1-4) was 8.8% (n=254). Respondents with sleep problemspast were more likely to be breathless, older with a higher BMI and sleep problems-present also included a higher likelihood of being female.After adjusting for age, sex and BMI, respondents with chronic breathlessness had 1.9 (95% CI=1.0 to 3.5) times the odds of sleep problems-past and sleep problems-current (adjusted OR=2.3; 95% CI=1.6 to 3.3).ConclusionsThere is a strong association between the two prevalent conditions. Future work will seek to understand if there is a causal relationship using validated sleep assessment tools and whether better managing one condition improves the other
Rectified voltage induced by a microwave field in a confined two-dimensional electron gas with a mesoscopic static vortex
We investigate the effect of a microwave field on a confined two dimensional
electron gas which contains an insulating region comparable to the Fermi
wavelength. The insulating region causes the electron wave function to vanish
in that region. We describe the insulating region as a static vortex. The
vortex carries a flux which is determined by vanishing of the charge density of
the electronic fluid due to the insulating region. The sign of the vorticity
for a hole is opposite to the vorticity for adding additional electrons. The
vorticity gives rise to non-commuting kinetic momenta. The two dimensional
electron gas is described as fluid with a density which obeys the Fermi-Dirac
statistics. The presence of the confinement potential gives rise to vanishing
kinetic momenta in the vicinity of the classical turning points. As a result,
the Cartesian coordinate do not commute and gives rise to a Hall current which
in the presence of a modified Fermi-Surface caused by the microwave field
results in a rectified voltage. Using a Bosonized formulation of the two
dimensional gas in the presence of insulating regions allows us to compute the
rectified current. The proposed theory may explain the experimental results
recently reported by J. Zhang et al.Comment: 14 pages, 2 figure
Isolation and characterization of the full-length cDNA encoding a member of a novel cytochrome p450 family (CYP320A1) from the tropical freshwater snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni
Cytochrome p450s (cyp450s) are a family of structurally related proteins, with diverse functions, including steroid synthesis and breakdown of toxins. This paper reports the full-length sequence of a novel cyp450 gene, the first to be isolated from the tropical freshwater snail Biomphalaria glabrata, an important intermediate host of Schistosoma mansoni. The nucleotide sequence is 2291 bp with a predicted amino acid sequence of 584aa. The sequence demonstrates conserved cyp450 structural motifs, but is sufficiently different from previously reported cyp450 sequences to be given a new classification, CYP320A1. Initially identified as down-regulated in partially resistant snails in response to S. mansoni infection, amplification of this gene using RT-PCR in both totally resistant or susceptible snail lines when exposed to infection, and all tissues examined, suggests ubiquitous expression. Characterization of the first cyp450 from B. glabrata is significant in understanding the evolution of these metabolically important proteins
A Survey on the Current Status and Future Challenges Towards Objective Skills Assessment in Endovascular Surgery
Minimally-invasive endovascular interventions have evolved rapidly over the past decade, facilitated by breakthroughs in medical
imaging and sensing, instrumentation and most recently robotics. Catheter based operations are potentially safer and applicable to
a wider patient population due to the reduced comorbidity. As a result endovascular surgery has become the preferred treatment
option for conditions previously treated with open surgery and as such the number of patients undergoing endovascular interventions
is increasing every year. This fact coupled with a proclivity for reduced working hours, results in a requirement for efficient training
and assessment of new surgeons, that deviates from the “see one, do one, teach one” model introduced by William Halsted, so
that trainees obtain operational expertise in a shorter period. Developing more objective assessment tools based on quantitative
metrics is now a recognised need in interventional training and this manuscript reports the current literature for endovascular skills
assessment and the associated emerging technologies. A systematic search was performed on PubMed (MEDLINE), Google Scholar,
IEEXplore and known journals using the keywords, “endovascular surgery”, “surgical skills”, “endovascular skills”, “surgical training
endovascular” and “catheter skills”. Focusing explicitly on endovascular surgical skills, we group related works into three categories
based on the metrics used; structured scales and checklists, simulation-based and motion-based metrics. This review highlights the
key findings in each category and also provides suggestions for new research opportunities towards fully objective and automated
surgical assessment solutions
Antipsychotics and Risk of Neuroleptic Malignant Syndrome: A Population-Based Cohort and Case-Crossover Study
BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available. OBJECTIVES: The aim of this study was to ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS. METHODS: We did a population-based study using data from the Hong Kong Hospital Authority’s Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91–120 days before the index date. To adjust for potential time trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications and acute medical conditions. RESULTS: 297,647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time trend, and case-crossover adjusted for time trend and potential confounders analysis were 8.00 (95% confidence interval 3.42–18.69), 5.88 (2.46–14.04), and 4.77 (1.95–11.66). CONCLUSIONS: Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded
Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study
OBJECTIVE
Low disease activity (LDA) and remission are emerging treat-to-target (T2T) endpoints in SLE. However, the rates at which these endpoints are met in patients with high disease activity (HDA) are unknown. Atacicept, which targets B lymphocyte stimulator and a proliferation-inducing ligand, improved disease outcomes in SLE patients with HDA (SLEDAI-2K ≥10) at baseline in the phase 2b ADDRESS II study. This is a post hoc analysis of T2T endpoints in these patients.
METHODS
Patients received weekly atacicept (75 or 150 mg s.c.) or placebo for 24 weeks (1:1:1 randomization). Attainment of three T2T endpoints, LDA (SLEDAI-2K ≤ 2), Lupus Low Disease Activity State (LLDAS) and remission (clinical SLEDAI-2K = 0, prednisone-equivalent ≤5mg/day and Physician’s Global Assessment <0.5), was assessed and compared with SLE Responder Index (SRI)-4 and SRI-6 response.
RESULTS
Of 306 randomized patients, 158 (51.6%) had baseline HDA. At week 24, 37 (23.4%) HDA patients attained LDA, 25 (15.8%) LLDAS and 17 (10.8%) remission. Each of these endpoints was more stringent than SRI-4 (n = 87; 55.1%) and SRI-6 (n = 67; 42.4%). Compared with placebo (n = 52), at week 24, patients treated with atacicept 150 mg (n = 51) were more likely to attain LDA [odds ratio (OR) 3.82 (95% CI: 1.44, 10.15), P = 0.007], LLDAS [OR 5.03 (95% CI: 1.32, 19.06), P = 0.018] or remission [OR 3.98 (95% CI: 0.78, 20.15), P = 0.095].
CONCLUSION
At week 24, LDA, LLDAS and remission were more stringent than SRI-4 and SRI-6 response, were attainable in the HDA population and discriminated between treatment with atacicept 150 mg and placebo. These results suggest that T2T endpoints are robust outcome measures in SLE clinical trials and support further evaluation of atacicept in SLE.
TRAIL REGISTRATION
ClinicalTrials.gov, http://clinicaltrials.gov, NCT01972568
Quantum gravity effects on statistics and compact star configurations
The thermodynamics of classical and quantum ideal gases based on the
Generalized uncertainty principle (GUP) are investigated. At low temperatures,
we calculate corrections to the energy and entropy. The equations of state
receive small modifications. We study a system comprised of a zero temperature
ultra-relativistic Fermi gas. It turns out that at low Fermi energy
, the degenerate pressure and energy are lifted. The
Chandrasekhar limit receives a small positive correction. We discuss the
applications on configurations of compact stars. As increases,
the radius, total number of fermions and mass first reach their nonvanishing
minima and then diverge. Beyond a critical Fermi energy, the radius of a
compact star becomes smaller than the Schwarzschild one. The stability of the
configurations is also addressed. We find that beyond another critical value of
the Fermi energy, the configurations are stable. At large radius, the increment
of the degenerate pressure is accelerated at a rate proportional to the radius.Comment: V2. discussions on the stability of star configurations added, 17
pages, 2 figures, typos corrected, version to appear in JHE
Impact of socioeconomic deprivation on rate and cause of death in severe mental illness
Background:
Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p>
Aims:
To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p>
Methods:
Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p>
Results:
Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001).
Discussion and conclusions:
Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed
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