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We have measured pressures p and temperatures T corresponding to the maximum nucleation rate of argon in a cryogenic supersonic nozzle apparatus where the estimated nucleation rates are J=10(17+/-1) cm(-3) s(-1). As T increases from 34 to 53 K, p increases from 0.47 to 8 kPa. Under these conditions, classical nucleation theory predicts nucleation rates of 11-13 orders of magnitude lower than the observed rates while mean field kinetic nucleation theory predicts the observed rates within 1 order of magnitude. The current data set appears consistent with the measurements of Iland et al. [J. Chem. Phys. 127, 154506 (2007)] in the cryogenic nucleation pulse chamber. Combining the two data sets suggests that classical nucleation theory fails because it overestimates both the critical cluster size and the excess internal energy of the critical clusters.

OBJECTIVES:
The aim of this study was to assess the feasibility of evaluation for appropriate use of radionuclide myocardial perfusion imaging (MPI) in multiple clinical sites and to determine use patterns as well as identify areas of apparent inappropriate use.

BACKGROUND:
Although cardiac imaging is highly valued for decision-making, the growth and expense related to these procedures has raised questions regarding overuse. The publication of appropriate use criteria (AUC), including those for MPI, were designed to provide guidance in the rational use of testing. However, limited data regarding the implementation and evaluation of AUC are available.

METHODS:
Six diverse clinical sites enrolled consecutive patients undergoing MPI, collecting point-of-service data entered into an online form. An automated algorithm assigned a specific indication from the AUC that was classified as appropriate, uncertain, or inappropriate. Site-specific feedback was later provided to each practice on ordering patterns.

RESULTS:
Of the 6,351 patients enrolled, 93% were successfully assigned an appropriateness level. Inappropriate use of MPI was found in 14.4% of patients, with a range of 4% to 22% among practices. Women and younger patients were more likely to undergo inappropriate MPI. Asymptomatic, low-risk patients accounted for 44.5% of inappropriate testing. Elimination of the 5 most common inappropriate use indications would reduce overall imaging volume by 13.2%. Inappropriate use by physicians from within the practice performing imaging was not greater than physicians outside of the practice. Educational feedback might have resulted in reduced inappropriate test ordering in 1 site.

CONCLUSIONS:
The tracking of appropriate use is feasible in clinical practice, with an automated system that can readily identify practice patterns and targets for educational and quality improvement initiatives. This approach might provide an alternative to utilization management.

Carotenoids have antioxidant and antiproliferative properties and may reduce the risk of breast cancer. We examined the association between dietary carotenoids and risk of invasive breast cancer in the Swedish Mammography Cohort, a population-based cohort of 36,664 women who completed a questionnaire in 1997. During a mean follow-up of 9.4 years, 1008 women were diagnosed with incident breast cancer. Dietary carotenoids were not significantly associated with the risk of breast cancer overall or with any subtype defined by oestrogen receptor (ER) and progesterone receptor (PR) status. However, dietary alpha-carotene and beta-carotene were inversely associated with the risk of ER-PR-breast cancer among ever smokers. Among ever smokers, the multivariable relative risks of ER-PR-breast cancer comparing the highest with the lowest quintile of intake were 0.32 (95% confidence interval (CI): 0.11-0.94; P(trend)=0.01) for alpha-carotene and 0.35 (95% CI: 0.12-0.99; P(trend)=0.03) for beta-carotene. The risk of breast cancer also decreased with increasing intakes of alpha-carotene (P(trend) = 0.02) and beta-carotene (P(trend)=0.01) among women who did not use dietary supplements. These findings suggest that dietary alpha-carotene and beta-carotene are inversely associated with the risk of breast cancer among smokers and among women who do not use dietary supplements.

The authors examined the association of dietary calcium and magnesium intake with all-cause, cardiovascular disease (CVD), and cancer mortality among 23,366 Swedish men, aged 45-79 years, who did not use dietary supplements. Cox proportional hazards regression models were used to estimate the multivariate hazard ratios and 95% confidence intervals of mortality. From baseline 1998 through December 2007, 2,358 deaths from all causes were recorded in the Swedish population registry; through December 2006, 819 CVD and 738 cancer deaths were recorded in the Swedish cause-of-death registry. Dietary calcium was associated with a statistically significant lower rate of all-cause mortality (hazard ratio (HR) = 0.75, 95% confidence interval (CI): 0.63, 0.88; P(trend) < 0.001) and a nonsignificantly lower rate of CVD (HR = 0.77, 95% CI: 0.58, 1.01; P(trend) = 0.064) but not cancer mortality (HR = 0.87, 95% CI: 0.65, 1.17; P(trend) = 0.362) when the highest intake tertile (mean = 1,953 mg/day; standard deviation (SD), 334) was compared with the lowest (990 mg/day; SD, 187). Dietary magnesium intake (means of tertiles ranged from 387 mg/day (SD, 31) to 523 mg/day (SD, 38) was not associated with all-cause, CVD, or cancer mortality. This population-based, prospective study of men with relatively high intakes of dietary calcium and magnesium showed that intake of calcium above that recommended daily may reduce all-cause mortality.

As population-based studies may obtain images from scanners with different field strengths, a method to normalize regional brain volumes according to intracranial volume (ICV) independent of field strength is needed. We found systematic differences in ICV estimation, tested in a cohort of healthy subjects (n=5) that had been imaged using 1.5T and 3T scanners, and confirmed in two independent cohorts. This was related to systematic differences in the intensity of cerebrospinal fluid (CSF), with higher intensities for CSF located in the ventricles compared with CSF in the cisterns, at 3T versus 1.5T, which could not be removed with three different applied bias correction algorithms. We developed a method based on tissue probability maps in MNI (Montreal Neurological Institute) space and reverse normalization (reverse brain mask, RBM) and validated it against manual ICV measurements. We also compared it with alternative automated ICV estimation methods based on Statistical Parametric Mapping (SPM5) and Brain Extraction Tool (FSL). The proposed RBM method was equivalent to manual ICV normalization with a high intraclass correlation coefficient (ICC=0.99) and reliable across different field strengths. RBM achieved the best combination of precision and reliability in a group of healthy subjects, a group of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and can be used as a common normalization framework.

CONTEXT:
Mounting evidence indicates that vitamin B(6), a coenzyme involved in nearly 100 enzymatic reactions, may reduce the risk of colorectal cancer.

OBJECTIVE:
To conduct a systematic review with meta-analysis of prospective studies assessing the association of vitamin B(6) intake or blood levels of pyridoxal 5'-phosphate (PLP; the active form of vitamin B(6)) with risk of colorectal cancer.

DATA SOURCES:
Relevant studies were identified by a search of MEDLINE and EMBASE databases to February 2010, with no restrictions. We also reviewed reference lists from retrieved articles.

STUDY SELECTION:
We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between vitamin B(6) intake or blood PLP levels and the risk of colorectal, colon, or rectal cancer.

DATA EXTRACTION:
Two authors independently extracted data and assessed study quality. Study-specific RRs were pooled using a random-effects model.

DATA SYNTHESIS:
Nine studies on vitamin B(6) intake and 4 studies on blood PLP levels were included in the meta-analysis. The pooled RRs of colorectal cancer for the highest vs lowest category of vitamin B(6) intake and blood PLP levels were 0.90 (95% CI, 0.75-1.07) and 0.52 (95% CI, 0.38-0.71), respectively. There was heterogeneity among studies of vitamin B(6) intake (P = .01) but not among studies of blood PLP levels (P = .95). Omitting 1 study that contributed substantially to the heterogeneity among studies of vitamin B(6) intake yielded a pooled RR of 0.80 (95% CI, 0.69-0.92). The risk of colorectal cancer decreased by 49% for every 100-pmol/mL increase (approximately 2 SDs) in blood PLP levels (RR, 0.51; 95% CI, 0.38-0.69).

CONCLUSION:
Vitamin B(6) intake and blood PLP levels were inversely associated with the risk of colorectal cancer in this meta-analysis.

Monocrotaline (MCT)-induces progressive disruption of endothelial cell membrane and caveolin-1 leading to pulmonary arterial hypertension (PAH). Treatment instituted early rescues caveolin-1 and attenuates PAH. To test the hypothesis that the poor response to therapy in established PAH is due to progressive deregulation of multiple signaling pathways, the authors investigated time-dependent changes in the expression of caveolin-1, gp130, PY-STAT3, Bcl-xL, and the molecules involved in NO signaling pathway (endothelial nitric oxide synthase [eNOS], heat sock protein 90 [HSP90], Akt, soluble guanylate cyclase [sGC] alpha1 and beta1 subunits). PAH and right ventricular hypertrophy (RVH) were observed at 2 and 3 weeks. Progressive loss of endothelial caveolin-1 and sGC (alpha1, beta1), PY-STAT3 activation, and Bcl-xL expression were observed at 1 to 3 weeks post-MCT. The expression of gp130 increased at 48 hours and 1 week, with a subsequent loss at 2 and 3 weeks. The expression of eNOS increased at 48 hours and 1 week post-MCT, with a significant loss at 3 weeks. The expression of HSP90 and Akt decreased at 2 and 3 weeks post-MCT concomitant with PAH. Thus, MCT induces progressive loss of membrane and cytosolic proteins, resulting in the activation of proliferative and antiapoptotic factors, and deregulation of NO signaling leading to PAH. An attractive therapeutic approach to treat PAH may be an attempt to rescue endothelial cell membrane integrity.

Interleukin (IL)-22 is a member of the IL-10 family of cytokines and represents an important effector molecule of activated Th22, Th1, and Th17 cells, as well as Tc-cell subsets, gammadelta T cells, natural killer (NK), and NKT cells. IL-22 mediates its effects via a heterodimeric transmembrane receptor complex consisting of IL-22R1 and IL-10R2 and subsequent Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathways including Jak1, Tyk2, and STAT3. Whereas in some aspects, IL-22 acts synergistically with tumor necrosis factor-alpha, IL-1beta, or IL-17, most functions of IL-22 are unique. Importantly, IL-22 does not serve the communication between immune cells. It mainly acts on epithelial cells and hepatocytes, where it favors the antimicrobial defense, regeneration, and protection against damage and induces acute phase reactants and some chemokines. This chapter illuminates in detail the properties of IL-22 with respect to its gene, protein structure, cellular sources, receptors, target cells, biological effects, and, finally, its role in chronic inflammatory diseases, tumors, and infection.

BACKGROUND:
The interrogation of proteomes ("proteomics") in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine.

METHODOLOGY/PRINCIPAL FINDINGS:
We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (~100 fM-1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states.

CONCLUSIONS/SIGNIFICANCE:
We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.

Alkylresorcinols (AR) in plasma samples have been suggested to be short- to medium-term biomarkers of whole grain wheat and rye intake. In the present study, we investigated whether AR are present in human adipose tissues, and if content correlated with long-term whole grain bread intake. Furthermore, we investigated if the relative AR homologue composition reflected what has been found previously in the habitual diet of Swedes. Biopsy samples (10-25 mg) from free-living Swedish women (n 20) were analysed by GC-MS. The mean total AR concentration in the samples was 0.54 (SD 0.35) microg/g, ranging from below limit of quantification ( < 0.08 microg/g) to 1.50 microg/g. Whole grain bread intake was significantly correlated with plasma total AR content (r 0.48, P < 0.05), and the C17 : 0/C21 : 0 ratio was 0.35 (sd 0.24), which is similar to what is found in plasma among free-living subjects consuming a mixed whole grain wheat and rye diet. These results suggest that AR in the adipose tissue should be evaluated as a long-term biomarker of whole grain wheat and rye intake.

Recent studies suggest that M. tuberculosis lineage and host genetics interact to impact how active tuberculosis presents clinically. We determined the phylogenetic lineages of M. tuberculosis isolates from participants enrolled in the Tuberculosis Trials Consortium Study 28, conducted in Brazil, Canada, South Africa, Spain, Uganda and the United States, and secondarily explored the relationship between lineage, clinical presentation and response to treatment. Large sequence polymorphisms and single nucleotide polymorphisms were analyzed to determine lineage and sublineage of isolates. Of 306 isolates genotyped, 246 (80.4%) belonged to the Euro-American lineage, with sublineage 724 predominating at African sites (99/192, 51.5%), and the Euro-American strains other than 724 predominating at non-African sites (89/114, 78.1%). Uneven distribution of lineages across regions limited our ability to discern significant associations, nonetheless, in univariate analyses, Euro-American sublineage 724 was associated with more severe disease at baseline, and along with the East Asian lineage was associated with lower bacteriologic conversion after 8 weeks of treatment. Disease presentation and response to drug treatment varied by lineage, but these associations were no longer statistically significant after adjustment for other variables associated with week-8 culture status.

BACKGROUND/OBJECTIVES:
Marine omega-3 fatty acids have beneficial effects on cardiovascular risk factors. Consumption of fatty fish and marine omega-3 has been associated with lower rates of cardiovascular diseases. We examined the association of fatty fish and marine omega-3 with heart failure (HF) in a population of middle-aged and older women.

SUBJECTS/METHODS:
Participants in the Swedish Mammography Cohort aged 48-83 years completed 96-item food-frequency questionnaires. Women without any history of HF, myocardial infarction or diabetes at baseline (n=36,234) were followed from 1 January 1998 until 31 December 2006 for HF hospitalization or mortality through Swedish inpatient and cause-of-death registers; 651 women experienced HF events. Cox proportional hazards models accounting for age and other confounders were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CI).

RESULTS:
Compared with women who did not eat fatty fish, RR were 0.86 (95% CI: 0.67, 1.10) for <1 serving per week, 0.80 (95% CI: 0.63, 1.01) for 1 serving per week, 0.70 (95% CI: 0.53, 0.94) for 2 servings per week and 0.91 (95% CI: 0.59, 1.40) for >or=3 servings per week (P(trend)=0.049). RR across quintiles of marine omega-3 fatty acids were 1 (reference), 0.85 (95% CI: 0.67, 1.07), 0.79 (95% CI: 0.61, 1.02), 0.83 (95% CI 0.65, 1.06) and 0.75 (95% CI: 0.58, 0.96) (P(trend)=0.04).

CONCLUSION:
Moderate consumption of fatty fish (1-2 servings per week) and marine omega-3 fatty acids were associated with a lower rate of first HF hospitalization or death in this population.

BACKGROUND:
Studies on alcohol intake in relation to endometrial cancer risk have produced inconsistent results.

METHODS:
For a meta-analysis, we identified cohort studies of alcohol and endometrial cancer by a literature search of Pub-Med and Embase up to 1 March 2010 and by searching the reference lists of relevant articles.

RESULTS:
Seven cohort studies, including 1,511,661 participants and 6086 endometrial cancer cases, were included in the dose-response random-effect meta-regression model. Compared with non-drinkers, women drinking less than 1 drink of alcohol (13 g of ethanol) per day had a lower risk for endometrial cancer; this risk was lower by 4% (95% confidence interval (95% CI): 0.93-1.00) for consumption up to 0.5 drink per day and by 7% (95% CI: 0.85-1.02) for consumption up to 1 drink. However, we found evidence of an increased risk for endometrial cancer for intakes higher than two alcoholic drinks per day: compared with non-drinkers, the risk was higher by 14% (95% CI: 0.95-1.36) for 2-2.5 drinks per day and by 25% (95% CI: 0.98-1.58) for >2.5 drinks per day.

CONCLUSION:
Our meta-analysis indicates a possible J-shaped relationship between alcohol intake and endometrial cancer risk.

The epsilon4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer's disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the epsilon4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of epsilon4 carriers (n = 67) vs. noncarriers (n = 24) with mild AD from the Alzheimer's Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.

Homogeneous nucleation rates of the n-alkanes (C(i)H(2i+2); i=7-10) were determined by combining information from pressure trace measurements and small angle x-ray scattering (SAXS) experiments in a supersonic Laval nozzle. The condensible vapor pressure p(J max), the temperature T(J max), the characteristic time Deltat(J max), and supersaturation S(J max) corresponding to the peak nucleation rate J(max) were determined during the pressure trace measurements. These measurements also served as the basis for the subsequent SAXS experiments. Fitting the radially averaged SAXS spectrum yielded the mean droplet radius r, 5

Foot wounds are the most common diabetes-related cause of hospitalization and frequently result in amputation. Although generally diagnosed clinically based on signs and symptoms of inflammation, empirical antibiotic treatment should be based on tissue cultures until resolution of infection. Advances in molecular detection over the past decade, including rapid chromogenic agar and real-time polymerase chain reaction, have improved diagnostic capabilities. However, chronic wounds may host biofilm bacteria not adequately detected by current microbiological testing. Enhanced DNA testing is required to identify these pathogens as well as evolving and previously underdiagnosed bacteria. Two options, nucleic acid fluorescent in situ hybridization and rDNA sequencing, are on the horizon for clinical use. Wound biofilms also necessitate more complex clinical management including debridement, augmenting host defenses, suppression of biofilms, and wound closure. Adopting these advances in diagnosis and treatment may help with overall prognosis and reduce health care costs.

No abstract given.

We review some of the many scientific results reported at a symposium held in September 2009 celebrating the 10th anniversary of National Aeronautics and Space Administration's (NASA's) Chandra X-ray Observatory. These results were contributed by scientists who were among the more than 300 symposium participants. We highlight those results that most emphasize the unique imaging and spectroscopic capabilities of Chandra.

BACKGROUND:
The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved.

METHODS:
We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided.

RESULTS:
Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, P(trend) = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, P(trend) = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, P(trend) = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05).

CONCLUSIONS:
Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study.

OBJECTIVE:
To investigate the association between hormone replacement therapy (HRT) and the incidence of cataract extraction among postmenopausal women.

DESIGN:
Population-based, prospective cohort study.

PARTICIPANTS:
A total of 30 861 postmenopausal women participating in the Swedish Mammography Cohort, age 49 to 83 years, who completed a self-administered questionnaire in 1997 about hormone status, HRT, and lifestyle factors.

METHODS:
The women were followed from September 1997 through October 2005. The cohort was matched with registers of cataract extraction in the study area.

MAIN OUTCOME MEASURES:
Incident operative extraction of age-related cataract.

RESULTS:
We identified 4324 incident cases of cataract extractions during 98 months of follow-up. In multivariate adjusted analysis, ever use of HRT was associated with a 14% increased risk of cataract extraction (rate ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21) compared with those who never used HRT. Current use of HRT was associated with an 18% increased risk of cataract extraction (RR, 1.18; 95% CI, 1.10-1.26). A significant linear trend was observed where increasing duration of HRT usage resulted in an increased risk of cataract extraction (P for trend = 0.006). Multivariate RR for current HRT usage for >10 years was 1.20 (95% CI, 1.06-1.36; P for trend = 0.001). Among women drinking on average >1 drink of alcohol per day, current HRT users had a 42% increased risk (RR, 1.42; 95% CI, 1.11-1.80) for cataract extraction, compared with women who neither used HRT nor alcohol. The risk of cataract extraction among current users of HRT was similar among current smokers and those who never smoked.

CONCLUSIONS:
Our prospective, population-based study indicates that postmenopausal women using HRT for a long period of time may be at an increased risk for cataract extraction, especially those drinking >1 alcoholic drink daily.

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