Management of patients with lower-risk myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis with abnormal blood cell development (dysplasia) leading to cytopenias and an increased risk for progression to acute myeloid leukemia (AML). Patients with MDS can generally be classified as lower- (LR-MDS) or higher-risk (HR-MDS). As treatment goals for patients with LR-MDS and those with HR-MDS differ significantly, appropriate diagnosis, classification, and follow-up are critical for correct disease management. In this review, we focus on the diagnosis, prognosis, and treatment options, as well as the prediction of the disease course and monitoring of treatment response in patients with LR-MDS. We discuss how next-generation sequencing, increasing knowledge on mechanisms of MDS pathogenesis, and novel therapies may change the current treatment landscape in LR-MDS and why structured assessments of responses, toxicities, and patient-reported outcomes should be incorporated into routine clinical practice

Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study.

BACKGROUND: The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. METHODS AND RESULTS: This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both -0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r=-0.19; P=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. CONCLUSIONS: Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required

A blind test of photometric redshift prediction

Results of a blind test of photometric redshift predictions against spectroscopic galaxy redshifts obtained in the Hubble Deep Field with the Keck Telescope are presented. The best photometric redshift schemes predict spectroscopic redshifts with a redshift accuracy of |Delta-z|<0.1 for more than 68 percent of sources and with |Delta-z|<0.3 for 100 percent, when single-feature spectroscopic redshifts are removed from consideration. This test shows that photometric redshift schemes work well at least when the photometric data are of high quality and when the sources are at moderate redshifts.Comment: 14 pp., accepted for publication in A

Complexity of Reconfiguration in Surface Chemical Reaction Networks

We analyze the computational complexity of basic reconfiguration problems for the recently introduced surface Chemical Reaction Networks (sCRNs), where ordered pairs of adjacent species nondeterministically transform into a different ordered pair of species according to a predefined set of allowed transition rules (chemical reactions). In particular, two questions that are fundamental to the simulation of sCRNs are whether a given configuration of molecules can ever transform into another given configuration, and whether a given cell can ever contain a given species, given a set of transition rules. We show that these problems can be solved in polynomial time, are NP-complete, or are PSPACE-complete in a variety of different settings, including when adjacent species just swap instead of arbitrary transformation (swap sCRNs), and when cells can change species a limited number of times (k-burnout). Most problems turn out to be at least NP-hard except with very few distinct species (2 or 3)

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

The DEEP Groth Strip Survey. I. The Sample

The Deep Extragalactic Exploratory Probe (DEEP) is a multi-phase research program dedicated to the study of the formation and evolution of galaxies and of large scale structure in the distant Universe. This paper describes the first five-year phase, denoted DEEP1. A series of ten DEEP1 papers will discuss a range of scientific topics (e.g., the study of photometric and spectral properties of a general distant galaxy survey, the evolution observed in galaxy populations of varied morphologies). The observational basis for these studies is the Groth Survey Strip field, a 127 square arcminute region which has been observed with the Hubble Space Telescope in both broad I-band and V-band optical filters and with the Low Resolution Imaging Spectrograph on the Keck Telescopes. Catalogs of photometric and structural parameters have been constructed for 11,547 galaxies and stars at magnitudes brighter than 29, and spectroscopy has been conducted for a magnitude-color weighted subsample of 818 objects. We evaluate three independent techniques for constructing an imaging catalog for the field from the HST data, and discuss the depth and sampling of the resultant catalogs. The selection of the spectroscopic subsample is discussed, and we describe the multifaceted approach taken to prioritizing objects of interest for a variety of scientific subprograms. A series of Monte Carlo simulations then demonstrates that the spectroscopic subsample can be adequately modeled as a simple function of magnitude and color cuts in the imaging catalog.Comment: ApJS accepted, 15 pages, 12 figures. Version with higher-quality figures available at http://astronomy.nmsu.edu/nicol

Photometric Redshifts of Quasars

We demonstrate that the design of the Sloan Digital Sky Survey (SDSS) filter system and the quality of the SDSS imaging data are sufficient for determining accurate and precise photometric redshifts (``photo-z''s) of quasars. Using a sample of 2625 quasars, we show that photo-z determination is even possible for z<=2.2 despite the lack of a strong continuum break that robust photo-z techniques normally require. We find that, using our empirical method on our sample of objects known to be quasars, approximately 70% of the photometric redshifts are correct to within delta z = 0.2; the fraction of correct photometric redshifts is even better for z>3. The accuracy of quasar photometric redshifts does not appear to be dependent upon magnitude to nearly 21st magnitude in i'. Careful calibration of the color-redshift relation to 21st magnitude may allow for the discovery of on the order of 10^6 quasars candidates in addition to the 10^5 quasars that the SDSS will confirm spectroscopically. We discuss the efficient selection of quasar candidates from imaging data for use with the photometric redshift technique and the potential scientific uses of a large sample of quasar candidates with photometric redshifts.Comment: 29 pages, 8 figures, submitted to A

Negative Aspects of Close Relationships as Risk Factors for Cognitive Aging

The extent to which social relationships influence cognitive aging is unclear. In this study, we investigated the association of midlife quality of close relationships with subsequent cognitive decline. Participants in the Whitehall II Study (n = 5,873; ages 45-69 years at first cognitive assessment) underwent executive function and memory tests 3 times over a period of 10 years (1997-1999 to 2007-2009). Midlife negative and positive aspects of close relationships were assessed twice using the Close Persons Questionnaire during the 8 years preceding cognitive assessment. Negative aspects of close relationships, but not positive aspects, were associated with accelerated cognitive aging. Participants in the top third of reported negative aspects of close relationships experienced a faster 10-year change in executive function (-0.04 standard deviation, 95% confidence interval: -0.08, -0.01) than those in the bottom third, which was comparable with 1 extra year of cognitive decline for participants aged 60 years after adjustment for sociodemographic and health status. Longitudinal analysis found no evidence of reverse causality. This study highlights the importance of differentiating aspects of social relationships to evaluate their unique associations with cognitive aging