Exercise responsive genes measured in peripheral blood of women with Chronic Fatigue Syndrome and matched control subjects

BACKGROUND: Chronic fatigue syndrome (CFS) is defined by debilitating fatigue that is exacerbated by physical or mental exertion. To search for markers of CFS-associated post-exertional fatigue, we measured peripheral blood gene expression profiles of women with CFS and matched controls before and after exercise challenge. RESULTS: Women with CFS and healthy, age-matched, sedentary controls were exercised on a stationary bicycle at 70% of their predicted maximum workload. Blood was obtained before and after the challenge, total RNA was extracted from mononuclear cells, and signal intensity of the labeled cDNA hybridized to a 3800-gene oligonucleotide microarray was measured. We identified differences in gene expression among and between subject groups before and after exercise challenge and evaluated differences in terms of Gene Ontology categories. Exercise-responsive genes differed between CFS patients and controls. These were in genes classified in chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport, and G protein-coupled receptor ontologies. Differences in ion transport and ion channel activity were evident at baseline and were exaggerated after exercise, as evidenced by greater numbers of differentially expressed genes in these molecular functions. CONCLUSION: These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS

Estuarine Processes and Their Stratigraphic Record: Paleosalinity and Sedimentation Changes in the Hudson Estuary (North America)

Paleosalinity estimates and rates of sedimentation inferred from core samples from the Hudson estuary for the interval between 6.4 and 1.3 ka indicate a possible role for the estuarine turbidity maximum (ETM) in influencing patterns of estuarine sedimentation at centennial to millennial time scales. Currently in the estuary, sedimentation is localized via sediment trapping particularly in the vicinity of the ETM, 13–26 km upstream from Battery Park (FBP) at the southern tip of Manhattan, in water depths greater than 4 m, and on the western side of the estuary. Data presented in this paper are from cores located within the segment of the estuary 29–50 km FBP. Age constraints are provided by C-14 dating. Paleoenvironmental interpretations are based upon paleosalinity estimates, grain size variability, and sedimentary structures. Paleosalinity was inferred on the basis of foraminiferal biofacies analysis and a new method for estimating summertime paleosalinity using oxygen isotope measurements in bivalve shell material. The isotopic analysis of a narrow size fraction (1.0–1.7 mm) representing summer growth of a single bivalve species (Gemma gemma) reduces the uncertainty related to annual changes in temperature. Data from ∼45 km FBP indicate a gradual decrease in summertime paleosalinity between 6.4 and 2.0 ka from 25–20‰ to 15–10‰ (the latter is similar to present-day values). These results are consistent with the conclusion of an earlier low-resolution study. Sedimentation rates are generally low and are similar to the rate of sea-level rise in the Hudson River. Lowest sedimentation rates are noted in short (lower than 2 m) cores from north of the Tappan Zee Bridge (40–50 km FBP from 2.4 ka to present); in shallow water (∼2 m at mean low water, core SD-11) ∼45 km FBP; and on the eastern side of the estuary from ∼50 to 29 km FBP. Exceptions are high sedimentation rates (up to four times background) observed in cores from the western flats (SD 30, ∼45 km FBP, 4.9 to 3.4 ka) in water depths of 4 m and from the western part of the main channel (P21.7 core, ∼32 km FBP, greater than 2.3 to ∼1.3 ka). We hypothesize that the observed pattern in sediment accumulation relates to a location for the ETM some 20 km upstream of its present position at 3 ka. Downstream migration of the ETM since 3 ka is ascribed to shoaling of the estuary, effectively squeezing the marine saltwater wedge in the same direction, and off marginal flats into the channel. Such shoaling would have enhanced the role of waves in mixing marine and fresher surface water, and reduced the effect of the ETM in focusing sediment accumulation. The results of this study are consistent with the idea that at any time, estuarine sedimentation is highly localized, suggesting a more complex depositional pattern than previously indicated in estuarine stratigraphic models

Once a feminist: Lynne Segal on Grace Paley’s The Little Disturbances of Man

The following contributions came in response to a request, sent to a number of key figures in feminism today, to write on a text that had been formative for their thinking as feminists. The chosen text could be a theory, a novel, an artwork, a performance, a poem: one that had stimulated, or even revolutionised, their ideas. As we hoped, this project has created a selection of texts central to our many and different experiences as feminists. I used to say that Margaret Drabble's The Garrick Year was the story of my life, in my early twenties, as if I was just a creature of time and circumstance. I read The Garrick Year sometime between October 1965, when my first child was born, and the end of 1967, before my marriage disintegrated. Like the heroine Emma Evans, I married a successful actor, had a child, and followed his career—which in the novel led Emma to Hereford for a summer season of plays

Identifying factors associated with sedentary time after stroke. Secondary analysis of pooled data from nine primary studies.

<p><b>Background</b>: High levels of sedentary time increases the risk of cardiovascular disease, including recurrent stroke.</p> <p><b>Objective</b>: This study aimed to identify factors associated with high sedentary time in community-dwelling people with stroke.</p> <p><b>Methods</b>: For this data pooling study, authors of published and ongoing trials that collected sedentary time data, using the activPAL monitor, in community-dwelling people with stroke were invited to contribute their raw data. The data was reprocessed, algorithms were created to identify sleep-wake time and determine the percentage of waking hours spent sedentary. We explored demographic and stroke-related factors associated with total sedentary time and time in uninterrupted sedentary bouts using unique, both univariable and multivariable, regression analyses.</p> <p><b>Results</b>: The 274 included participants were from Australia, Canada, and the United Kingdom, and spent, on average, 69% (SD 12.4) of their waking hours sedentary. Of the demographic and stroke-related factors, slower walking speeds were significantly and independently associated with a higher percentage of waking hours spent sedentary (p = 0.001) and uninterrupted sedentary bouts of <i>>30</i> and <i>>60 min</i> (p = 0.001 and p = 0.004, respectively). Regression models explained 11–19% of the variance in total sedentary time and time in prolonged sedentary bouts.</p> <p><b>Conclusion</b>: We found that variability in sedentary time of people with stroke was largely unaccounted for by demographic and stroke-related variables. Behavioral and environmental factors are likely to play an important role in sedentary behavior after stroke. Further work is required to develop and test effective interventions to address sedentary behavior after stroke.</p

Risk factors for rehospitalization for acute coronary syndromes and unplanned revascularization following acute myocardial infarction

Background Rehospitalizations for acute coronary syndromes (ACS) and coronary revascularization after an acute myocardial infarction (AMI) are not only common and costly but can also impact patients’ quality of life. In contrast to mortality and all‐cause readmissions, little insight is available into risk factors associated with ACS and revascularization after AMI. Methods and Results In a multicenter AMI registry, we examined the rates and predictors of rehospitalizations for ACS and revascularization within the year after AMI among 3283 patients. Staged revascularization procedures were excluded. Kaplan–Meier estimated rates of rehospitalization due to ACS and revascularization were 6.8% and 4.1%, respectively. In hierarchical, multivariable models, the strongest predictors of rehospitalization for ACS were coronary artery bypass graft prior to AMI hospitalization (hazard ratio [HR] 2.12, 95% CI 1.45 to 3.10), female sex (HR 1.67, 95% CI 1.23 to 2.25), and in‐hospital PCI (HR 1.85, 95% CI 1.28 to 2.69). The strongest predictors of subsequent revascularization were multivessel disease (HR 2.89, 95% CI 1.90 to 4.39) and in‐hospital percutaneous coronary intervention with a bare metal stent (HR 2.08, 95% CI 1.19 to 3.63). The Global Registry of Acute Coronary Events mortality risk score was not associated with the risk of rehospitalization for ACS or revascularization. Conclusions Unique characteristics are associated with admissions for ACS and revascularization, as compared with survival. These multivariable risk predictors may help identify patients at high risk for ACS and revascularization, in whom intensification of secondary prevention therapies or closer post‐AMI follow‐up may be warranted

Health Status Outcomes in Patients With Acute Myocardial Infarction After Rehospitalization

Background Rehospitalizations after acute myocardial infarction for unplanned coronary revascularization and unstable angina (UA) are common. However, despite the inclusion of these events in composite end points of many clinical trials, their association with health status has not been studied. Methods and Results We included 3283 patients with acute myocardial infarction enrolled in a prospective, 24-center US study who had rehospitalizations independently classified by experienced cardiologists. Health status was assessed using Seattle Angina Questionnaire and EuroQol-5D Visual Analog Scale. In the propensity-matched cohorts, 1-year health status was compared between those who did and did not experience rehospitalization for UA or revascularization using a hierarchical linear model. Overall, mean age was 59 years, 33% were women, and 70% were white. Rehospitalization rates for UA and unplanned revascularization at 1 year were 4.3% and 4.7%. One-year Seattle Angina Questionnaire summary scores were worse in patients with rehospitalizations for UA (mean difference, -10.1; 95% confidence interval, -12.4 to -7.9) and unplanned revascularization (mean difference, -5.7; 95% confidence interval, -8.8 to -2.5) when compared with patients without such rehospitalizations. Similarly, EuroQol-5D Visual Analog Scale scores were worse among patients with such readmissions. Individual Seattle Angina Questionnaire domains indicated worse 1-year angina and quality of life outcomes among patients rehospitalized for UA or unplanned revascularization. Conclusions Within the first year after acute myocardial infarction, rehospitalizations for UA and unplanned revascularization are associated with worse health status. These findings highlight the impact of such events from a patient's perspective, beyond their economic impact and support the use of UA and unplanned revascularization as elements of composite end points

Factors Affecting the Pharmacokinetics and Pharmacodynamics of PEGylated Liposomal Irinotecan (IHL-305) in Patients with Advanced Solid Tumors

IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11). The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW]) were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time curve (AUC) to sum total CPT-11 AUC. Patients aged \u3c60 years had a 1.3-fold higher ratio of percent decrease in monocytes at nadir to percent decrease in absolute neutrophil count at nadir as compared with patients aged ≥60 years. There was an inverse relationship between patient age and percent decrease in monocytes at nadir, ie, younger patients have a higher percent decrease in monocytes. Patients with a higher percent decrease in monocytes at nadir have a decreased plasma exposure of sum total CPT-11. The pharmacokinetics and pharmacodynamics of IHL-305 are consistent with those of other PEGylated liposomal carriers. Interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 was associated with age, body composition, and monocytes

Meeting the Cool Neighbors VII: Spectroscopy of faint, red NLTT dwarfs

We present low-resolution optical spectroscopy and BVRI photometry of 453 candidate nearby stars drawn from the NLTT proper motion catalogue. The stars were selected based on optical/near-infrared colours, derived by combining the NLTT photographic data with photometry from the 2MASS Second Incremental Data Release. Based on the derived photometric and spectroscopic parallaxes, we identify 111 stars as lying within 20 parsecs of the Sun, including 9 stars with formal distance estimates of less than 10 parsecs. A further 53 stars have distance estimates within 1-sigma of our 20-parsec limit. Almost all of those stars are additions to the nearby star census. In total, our NLTT-based survey has so far identified 496 stars likely to be within 20 parsecs, of which 195 are additions to nearby-star catalogues. Most of the newly-identified nearby stars have spectral types between M4 and M8.Comment: 41 pages, 7 figure