192 research outputs found
Recommended from our members
The Role of Tobacco, Alcohol, and Obesity in Neoplastic Progression to Esophageal Adenocarcinoma: A Prospective Study of Barrett's Esophagus
Background: Esophageal adenocarcinoma (EA) incidence in many developed countries has increased dramatically over four decades, while survival remains poor. Persons with Barrett's esophagus (BE), who experience substantially elevated EA risk, are typically followed in surveillance involving periodic endoscopy with biopsies, although few progress to EA. No medical, surgical or lifestyle interventions have been proven to safely lower EA risk. Design: We investigated whether smoking, obesity or alcohol could predict progression to EA in a prospective cohort of 411 BE patients. Data were collected during personal interview. Adjusted hazard ratios (HR) were estimated using Cox regression. Results: 39% had body mass index (BMI) over 30 and 64% had smoked cigarettes. Main analyses focused on those with at least 5 months of follow-up (33,635 person-months), in whom 45 developed EA. Risk increased by 3% per year of age (trend p-value 0.02), with approximate doubling of risk among males. EA risk increased with smoking pack-years (trend p-value 0.04) and duration (p-value 0.05). Compared to never-smokers, the HR for those in the highest pack-year tertile was 2.29 (95%CI 1.04–5.07). No association was found with alcohol or BMI, whereas a suggestion of increased risk was observed in those with higher waist-hip ratio, especially among males. Conclusion: EA risk significantly increased with increasing age and cigarette exposure. Abdominal obesity, but not BMI, was associated with a modest increased risk. Continued follow-up of this and other cohorts is needed to precisely define these relationships so as to inform risk stratification and preventive interventions
Traffic-Related Air Pollution and All-Cause Mortality during Tuberculosis Treatment in California.
BackgroundAmbient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain.ObjectiveWe determined the impact of residential traffic on mortality during treatment of active TB.MethodsFrom 2000-2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in 100- to 400-m radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests.ResultsParticipants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the 100-m buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio (HR)=1.03 [95% confidence interval (CI): 0.86, 1.25]; third quintile HR=1.14 (95% CI: 0.95, 1.37); fourth quintile HR=1.19 (95% CI: 0.99, 1.43); fifth quintile HR=1.28 (95% CI: 1.07, 1.53), respectively; p-trend=0.002].ConclusionsResidential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699
Geographic distribution and genetic diversity of the Ehrlichia sp. from Panola Mountain in Amblyomma americanum
Background:
A novel Ehrlichia, closely related to Ehrlichia ruminantium, was recently discovered from Panola Mountain State Park, GA, USA. We conducted a study to determine if this agent was recently introduced into the United States.
Methods:
We developed a sensitive PCR assay based on the conserved gltA (citrate synthase) gene and tested DNA samples extracted from 1964 field-collected and 1835 human-biting Amblyomma americanum from 23 eastern states of the USA.
Results:
The novel agent was detected in 36 ticks collected from 10 states between 1998 and 2006. Infected ticks were collected both from vegetation (n = 14, 0.7%) and from humans (n = 22, 1.2%). Fragments of the conserved gltA gene and the variable map1 gene were sequenced from positive samples. Two distinct clades, with 10.5% nucleic acid divergence over the 730 bp map1 sequence, were identified.
Conclusion:
These data suggest that the Panola Mountain Ehrlichia was not recently introduced to the United States; this agent has an extensive distribution throughout the range of its tick vector, has been present in some locations for several years, and displays genetic variability. Furthermore, people in several states were exposed to this agent through the bite of infected ticks, underscoring the potential public health risk of this emerging ehrlichiosis
Low-dose cyclophosphamide induces anti-tumor T-cell responses which associate with survival in metastatic colorectal cancer
Purpose: Anti-cancer T-cell responses can control tumors, but immune-suppressive mechanisms in vivo prevent their function. The role of regulatory T-cells (Tregs) in metastatic colorectal cancer (mCRC) is unclear. We have previously shown depletion of Tregs enhances CRC-specific effector T-cell responses. Low dose cyclophosphamide (CPM) targets Tregs in animal models and some human studies, however the effect of CPM in mCRC is unknown. Experimental Design: Fifty-five mCRC patients were enrolled onto a phase I/II trial and randomized to receive two week-long courses of low-dose (50mg twice-a-day) CPM or not. The absolute number, phenotype and anti-tumor function of peripheral blood-derived lymphocyte subsets were monitored throughout treatment, along with 18-month follow-up. Results: Initially CPM reduced proliferation in all lymphocyte subsets, however, a rapid mobilization of effector T-cells overcame this decrease, leading to increased absolute T-cell numbers. In contrast, a reduction in proportional and absolute Treg, B-cell and NK-cell numbers occurred. The expansion and subsequent activation of effector T-cells was focused on tumor-specific T-cells, producing both granzyme B and IFN-gamma. CPM-treated patients demonstrating the most enhanced IFN-gamma+ tumor-specific T-cell responses exhibited a significant delay in tumor progression (HR=0.29, 95% CI 0.12-0.69, P=0.0047), compared to non-responders and no-treatment controls. Conclusions: CPM-induced Treg-depletion is mirrored by a striking boost to anti-tumor immunity. This study provides the first direct evidence of the benefit of naturally primed T-cells in mCRC patients. Our results also support the concept that non-mutated self-antigens can act as useful targets for immunotherapies
Cell proliferation, cell cycle abnormalities, and cancer outcome in patients with Barrett’s esophagus: A long-term prospective study
Purpose: Elevated cellular proliferation and cell cycle abnormalities, which have been associated with
premalignant lesions, may be caused by inactivation of tumor suppressor genes. We measured
proliferative and cell cycle fractions of biopsies from a cohort of patients with Barrett's esophagus to
better understand the role of proliferation in early neoplastic progression and the association between cell
cycle dysregulation and tumor suppressor gene inactivation.
Experimental Design: Cell proliferative fractions (determined by Ki67/DNA multiparameter flow
cytometry) and cell cycle fractions (DNA content flow cytometry) were measured in 853 diploid biopsies
from 362 patients with Barrett's esophagus. The inactivation status of CDKN2A and TP53 was assessed in
a subset of these biopsies in a cross-sectional study. A prospective study followed 276 of the patients
without detectable aneuploidy for an average of 6.3 years with esophageal adenocarcinoma as an
endpoint.
Results: Diploid S and 4N (G2/tetraploid) fractions were significantly higher in biopsies with TP53
mutation and LOH. CDKN2A inactivation was not associated with higher Ki67-positive, diploid S, G1, or
4N fractions. High Ki67-positive and G1 phase fractions were not associated with the future development
of esophageal adenocarcinoma (p=0.13 and p=0.15, respectively), while high diploid S phase and 4N
fractions were (p=0.03 and p<0.0001, respectively).
Conclusions: High Ki67-positive proliferative fractions were not associated with inactivation of CDKN2A
and TP53 or future development of cancer in our cohort of patients with Barrett's esophagus. Bi-allelic
inactivation of TP53 was associated with elevated 4N fractions, which have been associated with the
future development of esophageal adenocarcinoma
model of superconducting UPt
The phase diagram of superconducting UPt is explained in a
Ginzburg-Landau theory starting from the hypothesis that the order parameter is
a pseudo-spin singlet which transforms according to the representation
of the point group. We show how to compute the positions of the phase
boundaries both when the applied field is in the basal plane and when it is
along the c-axis. The experimental phase diagrams as determined by longitudinal
sound velocity data can be fit using a single set of parameters. In particular
the crossing of the upper critical field curves for the two field directions
and the apparent isotropy of the phase diagram are reproduced. The former is a
result of the magnetic properties of UPt and their contribution to the free
energy in the superconducting state. The latter is a consequence of an
approximate particle-hole symmetry. Finally we extend the theory to finite
pressure and show that, in contrast to other models, the model
explains the observed pressure dependence of the phase boundaries.Comment: RevTex, 29 pages, 18 PostScript figures in a uuencoded, gzipped tar
file. PostScript version of paper, tar file of PostScript figures and
individual PostScript figures are also available via anonymous ftp at
ftp://nym.physics.wisc.edu/anonymou/papers/upt3
Recommended from our members
NSAIDs Modulate Clonal Evolution in Barrett's Esophagus
Cancer is considered an outcome of decades-long clonal evolution fueled by acquisition of somatic genomic abnormalities (SGAs). Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce cancer risk, including risk of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). However, the cancer chemopreventive mechanisms of NSAIDs are not fully understood. We hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. We evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5–8 time points over 6.4–19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1–8.6) off-NSAIDs and 0.6 (95% SI 0.3–1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two we detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs
Colouration in amphibians as a reflection of nutritional status : the case of tree frogs in Costa Rica
Colouration has been considered a cue for mating success in many species; ornaments in males often are related to carotenoid mobilization towards feathers and/or skin and can signal general health and nutrition status. However, there are several factors that can also link with status, such as physiological blood parameters and body condition, but there is not substantial evidence which supports the existence of these relationships and interactions in anurans. This study evaluated how body score and blood values interact with colouration in free-range Agalychnis callidryas and Agalychnis annae males. We found significant associations between body condition and plasmatic proteins and haematocrit, as well as between body condition and colour values from the chromaticity diagram. We also demonstrated that there is a significant relation between the glucose and plasmatic protein values that were reflected in the ventral colours of the animals, and haematocrit inversely affected most of those colour values. Significant differences were found between species as well as between populations of A. callidryas, suggesting that despite colour variation, there are also biochemical differences within animals from the same species located in different regions. These data provide information on underlying factors for colouration of male tree frogs in nature, provide insights about the dynamics of several nutrients in the amphibian model and how this could affect the reproductive output of the animals
Effects of Experimental Brood Size Manipulation and Gender on Carotenoid Levels of Eurasian Kestrels Falco tinnunculus
Animals use carotenoid-pigments for coloration, as antioxidants and as enhancers of the immune system. Carotenoid-dependent colours can thus signal individual quality and carotenoids have also been suggested to mediate life-history trade-offs.
Single Spin Superconductivity: Formulation and Ginzburg-Landau Theory
We describe a novel superconducting phase that arises due to a pairing
instability of the half-metallic antiferromagnetic (HM AFM) normal state. This
single spin superconducting (SSS) phase contains broken time reversal symmetry
in addition to broken gauge symmetry, the former due to the underlying magnetic
order in the normal state. A classification of normal state symmetries leads to
the conclusion that the HM AFM normal phase whose point group contains the
inversion operator contains the least symmetry possible which still allows for
a zero momentum pairing instability. The Ginzburg-Landau free energy for the
superconducting order parameter is constructed consistent with the symmetry of
the normal phase, electromagnetic gauge invariance and the crystallographic
point group symmetry including inversion. For cubic, hexagonal and tetragonal
point groups, the possible symmetries of the superconducting phase are
classified, and the free energy is used to construct a generalized phase
diagram. We identify the leading candidate out of the possible SSS phases for
each point group. The symmetry of the superconducting phase is used to
determine the cases where the gap function has generic zeros (point or line
nodes) on the Fermi surface. Such nodes always occur, hence thermodynamic
properties will have power-law behavior at low temperature.Comment: 39 pages, RevTeX, 4 PostScript figures included, submitted to Phys.
Rev.
- …