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The motion of S2, one of the stars closest to the Galactic Centre, has been measured accurately and used to study the compact object at the centre of the Milky Way. It is commonly accepted that this object is a supermassive black hole, but the nature of its environment is open to discussion. Here, we investigate the possibility that dark matter in the form of an ultralight scalar field 'cloud' clusters around Sgr A*. We use the available data for S2 to perform a Markov Chain Monte Carlo analysis and find the best-fit estimates for a scalar cloud structure. Our results show no substantial evidence for such structures. When the cloud size is on the order of the size of the orbit of S2, we are able to constrain its mass to be smaller than 0.1 % of the central mass, setting a strong bound on the presence of new fields in the galactic centre. [ABSTRACT FROM AUTHOR]

Barrett's esophagus ( BE), a complication of gastroesophageal reflux disease, is associated with an increased risk of esophageal cancer. Mitogen-activated protein kinases may play an important role in the pathogenesis of this process. We aimed to evaluate mitogen-activated protein kinases activity in esophageal mucosa of patients with BE and find possible relationship between reflux type and BE. Twenty-four patients (mean age: 59 years) with gastroesophageal reflux disease symptoms and endoscopically suspected esophageal metaplasia ( ESEM) were prospectively enrolled for testing by a multichannel intraluminal impedance monitoring along with a Bilitec 2000. Endoscopic biopsies were taken from methylene blue-positive pit patterns (sites suggesting specialized intestinal metaplasia [ SIM]), from 2 cm above the Z-line and from cardial parts of the stomach. The biopsies were analyzed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 activity by Western blot. Seventeen ESEMs had histologically proven metaplasia: eight patients had SIM and nine had gastric-type epithelia ( GE). Biliary reflux was more evident in SIM ( P = 0.019) but not in GE ( P = 0.019); non-biliary reflux was typical for GE ( P = 0.005) but not for SIM ( P = 0.04). Strong activations of ERK and p38 were found predominantly in SIM, but not in normal esophageal mucosa ( NE) ( P = 0.01 and P < 0.001 respectively). Strong signals for active JNK and p38 were detected in GE, but not in NE ( P = 0.006 and P = 0.02 respectively). ERK activity was significantly higher than p38 activity in ESEM patients only with GE ( P = 0.02). The strong activation of ERK, but not JNK is indicative of SIM. The presence of bile in gastroesophageal refluxate is predisposing to SIM, but not to GE in esophageal mucosa. [ABSTRACT FROM AUTHOR]

Rainfall gradients select for contrasting, integrated, adaptive strategies in the Mediterranean legume, Lupinus luteus, where phenology, productivity, fecundity, and water-use are matched to seasonal rainfall. Profligate high-rainfall ecotypes have developed drought tolerance that is redundant in drought-avoiding low-rainfall ecotypes.Our understanding of within-species annual plant adaptation to rainfall gradients is fragmented. Broad-scale ecological applications of Grime’s C-S-R triangle are often superficial, while detailed drought physiology tends to be narrow, focusing on elite cultivars. The former lack the detail to explain how plants respond, while the latter provide little context to investigate trade-offs among traits, to explain where/why these might be adaptive. Ecophysiology, combining the breadth of the former with the detail of the latter, can resolve this disconnect and is applied here to describe adaptive strategies in the Mediterranean legume Lupinus luteus. Wild and domesticated material from low- and high-rainfall environments was evaluated under contrasting terminal drought. These opposing environments have selected for contrasting, integrated, adaptive strategies. Long-season, high-rainfall habitats select for competitive (C) traits: delayed phenology, high above- and below-ground biomass, productivity, and fecundity, leading to high water-use and early stress onset. Terminal drought-prone environments select for the opposite: ruderal (R) traits that facilitate drought escape/avoidance but limit reproductive potential. Surprisingly, high-rainfall ecotypes generate lower critical leaf water potentials under water deficit, maintaining higher relative water content than the latter. Given that L. luteus evolved in sandy, low-water-holding capacity soils, this represents a bet-hedging response to intermittent self-imposed water-deficits associated with a strongly C-selected adaptive strategy that is therefore redundant in R-selected low-rainfall ecotypes. Domesticated L. luteus is even more R-selected, reflecting ongoing selection for early maturity. Introgression of appropriate C-selected adaptive traits from wild germplasm may widen the crop production range. [ABSTRACT FROM PUBLISHER]

Background: Marfan syndrome is a heritable connective tissue disease. Definitive diagnosis is complex, and requires sequencing of a large gene, FBN1.Aim: We aimed to develop a simple model to estimate the pre-test probability of Marfan syndrome.Design: Prospective cross-sectional study.Methods: We applied diagnostic standards for definitive diagnosis or exclusion of Marfan syndrome in 329 consecutive persons. In 208 persons with random assignment to our derivation group, we performed multivariate logistic regression to assess 14 clinical variables for inclusion in a prediction model with derivation of score points from the estimated coefficients. We created cut-offs to classify low, moderate and high probability of Marfan syndrome. For validation, we applied the model to the remaining 121 persons.Results: We identified seven variables for inclusion in the final model, where we assigned four score points to ectopia lentis, two points to a family history of Marfan syndrome, and one point to previous thoracic aortic surgery, to pectus excavatum, to a wrist and thumb sign, to previous pneumothorax, and to skin striae. In the derivation group 12, 42 and 92% of persons with low (&leq;1 point), moderate (>1–3.5 points) or high pre-test probability (>3.5 points) had Marfan syndrome, compared to 12, 57 and 91%, respectively, in the validation group. Positive likelihood ratios were 13.96 and 8.54 in the high probability group of the derivation and validation group, respectively.Conclusions: A simple prediction model provides evidence for Marfan syndrome. This model can be used to identify patients who require definitive diagnostic work-up. [ABSTRACT FROM PUBLISHER]

Objectives This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. Methods A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. Results Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9–6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2–6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4–10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. Conclusions Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential. [ABSTRACT FROM PUBLISHER]

In mammals, posttesticular epididymal sperm maturation is considered an essential step in the transformation of immature testicular gametes to mature spermatozoa capable of fertilization. Reactive oxygen species (ROS) have been shown to be key actors in this maturation process, and it is now clear that ROS are central for sperm physiology in processes such as sperm maturation and capacitation. However, during epididyrnal maturation and storage and until the onset of fertilization, oxidative damage is a threat spermatozoa must face more than any other cells. Spermatozoa were found to be extremely sensitive to oxidative attacks correlated with lipid peroxidation, DNA damage, and impaired sperm motility, all affecting fertilization. To control the quantity of H2O2 in the vicinity of male gametes, mammalian epididymis uses a panel of nonenzymatic and enzymatic scavengers, among which the glutathione peroxidase (GPx) family is largely represented. Among the various GPx proteins expressed in the mammalian epididyrnis, GPx4 and GPx5 occupy unique positions and functions that are reviewed in this paper. This paper underlines the importance of the GPx protein family in determining the fertilizing potential of mammalian spermatozoa. This is particularly relevant in the field of mammalian fertility and infertility as well as in the development of assisted medical procreation technologies and male gamete preservation techniques that are extensively used in human and animal reproduction programs. [ABSTRACT FROM AUTHOR]

We present the first high angular resolution observation of the B[e] star/X-ray transient object CI Cam, performed with the two-telescope Infrared Optical Telescope Array (IOTA), its upgraded three-telescope version (IOTA3T) and the Palomar Testbed Interferometer (PTI). Visibilities and closure phases were obtained using the IONIC-3 integrated optics beam combiner. CI Cam was observed in the near-infrared H and K spectral bands, wavelengths well suited to measure the size and study the geometry of the hot dust surrounding CI Cam. The analysis of the visibility data over an 8 yr period from soon after the 1998 outburst to 2006 shows that the dust visibility has not changed over the years. The visibility data show that CI Cam is elongated which confirms the disc-shape of the circumstellar environment and totally rules out the hypothesis of a spherical dust shell. Closure phase measurements show direct evidence of asymmetries in the circumstellar environment of CI Cam and we conclude that the dust surrounding CI Cam lies in an inhomogeneous disc seen at an angle. The near-infrared dust emission appears as an elliptical skewed Gaussian ring with a major axis , an axis ratio and a position angle . [ABSTRACT FROM AUTHOR]

We have detected asymmetry in the symbiotic star CH Cyg through the measurement of precision closure phase with the Integrated Optics Near-Infrared Camera (IONIC) beam combiner, at the infrared optical telescope array interferometer. The position of the asymmetry changes with time and is correlated with the phase of the 2.1-year period found in the radial velocity measurements for this star. We can model the time-dependent asymmetry either as the orbit of a low-mass companion around the M giant or as an asymmetric, 20 per cent change in brightness across the M giant. We do not detect a change in the size of the star during a 3-year monitoring period neither with respect to time nor with respect to wavelength. We find a spherical dust shell with an emission size of 2.2 ± 0.1 D* full width at half-maximum around the M giant star. The star to dust flux ratio is estimated to be 11.63 ± 0.3. While the most likely explanation for the 20 per cent change in brightness is non-radial pulsation, we argue that a low-mass companion in close orbit could be the physical cause of the pulsation. The combined effect of pulsation and low-mass companion could explain the behaviour revealed by the radial velocity curves and the time-dependent asymmetry detected in the closure-phase data. If CH Cyg is a typical long secondary period variable then these variations could be explained by the effect of an orbiting low-mass companion on the primary star. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite multiple publications on effects of rehabilitation in cardiac patients, rehabilitation is not fully known to be of value in post-percutaneous coronary intervention (PCI) patients. AIMS: To investigate the influence of cardiac rehabilitation on the incidence of major adverse cardiac events (MACEs) in post-PCI patients. METHODS: Retrospectively and nonrandomized 140 post-PCI patients (107 males, mean age 62 (7) years) participated in a 3-month rehabilitation program, starting 2 weeks post-PCI, while 83 post-PCI patients (54 males, mean age 68 (8) years) did not and were all followed up for 15 months. Data on cardiac medication prescription and incidence of MACE (including angina pectoris with or without reintervention, restenosis, myocardial infarction, revascularisation with re-PCI or CABG, and death) were collected. The relationship with cardiovascular risk factors including sex, smoking behaviour, obesity, diabetes mellitus, hypertension, familiar predisposition, and hypercholesterolemia was analysed. RESULTS: The incidence of total MACE in the rehabilitation group is significantly lower than in the control group (24% vs. 42%, respectively; P<0.005). The incidence of documented restenosis, angina pectoris with resulting reintervention, all revascularisations, and death is significantly lower in the rehabilitation group, compared with the control group. CONCLUSION: The incidence of MACE and restenosis is significantly lower when PCI patients are included in a cardiac rehabilitation program. [ABSTRACT FROM AUTHOR]

Objective.To identify potential predictors and correlates of compliance and to examine differences between patient and provider perspectives on compliance.Patients.One hundred eighty-four patients (84 men and 96 women) were recruited from a chronic pain treatment program for this telephone follow-up study.Results.Health care providers (HCPs) reported making more recommendations than patients reported hearing. Patients rated themselves as more compliant than did HCPs. Overall compliance rates at a >6-month follow-up were 89% from the patients' perspective and 70% from the HCPs' perspective. HCPs rated compliance specific to psychological care as more related to positive outcomes than did patients. Participants' pain and anxiety ratings at a >6-month follow-up and satisfaction with treatment were significantly associated with patients' compliance ratings. For HCP-rated compliance, only HCPs' perceived benefit and interference from compliance were associated.Conclusion.Results suggest important disparities between HCPs and patients on remembered recommendations, levels of compliance, and health-related importance of complying with recommendations. [ABSTRACT FROM AUTHOR]

Background Acne is a common skin disorder, but epidemiological data from the general population obtained by examination are scarce. Clinical experience suggests an association between smoking and acne, although confirmatory evidence from appropriate studies is lacking.Objectives To determine the prevalence and demographic factors of acne in a general population sample and to investigate the association of smoking and acne on a qualitative and quantitative level.Methods In a cross-sectional study, 896 citizens (aged 1–87 years, median 42) of the City of Hamburg were dermatologically examined. The prevalence and severity of acne were recorded and further information on demographic variables, medical history, and alcohol and cigarette consumption were obtained by a standardized interview.Results According to the clinical examination, acne was present in 26·8% overall, and was more prevalent in men (29·9%) than women (23·7%) (odds ratio, OR 1·37, 95% confidence interval, CI 1·01–1·87). Prevalence followed a significant linear trend over age with peak prevalence between 14 and 29 years (P < 0·001). The reported age at onset was significantly lower in women than men (P = 0·015). According to multiple logistic regression analyses acne prevalence was significantly higher in active smokers (40·8%, OR 2·04, 95% CI 1·40–2·99) as compared with non-smokers (25·2%). A significant linear relationship between acne prevalence and number of cigarettes smoked daily was obtained (trend test: P < 0·0001). In addition, a significant dose-dependent relationship between acne severity and daily cigarette consumption was shown by linear regression analysis (P = 0·001).Conclusions Smoking is a clinically important contributory factor to acne prevalence and severity. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence supports the hypotheses that the retinoic acid receptor beta2 (RAR-beta2) gene is a tumor suppressor gene and that the chemopreventive effects of retinoids are due to induction of RAR-beta2. RAR-beta2 expression is reduced in many malignant tumors, and we examined whether methylation of RAR-beta2 could be responsible for this silencing.Methods: RAR-beta2 expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) analysis in eight breast cancer cell lines that were either treated with the demethylating agent 5-aza-2'-deoxycytidine and subsequently with all-trans-retinoic acid (ATRA) or left untreated. Sodium bisulfite genomic sequencing was used to determine the locations of 5-methylcytosines in the RAR-beta2 genes of three of these cell lines. In 16 breast cancer biopsy specimens and non-neoplastic breast tissue, methylation-specific PCR was used to determine the methylation status of RAR-beta2, and, in 13 of the specimens, RT-PCR analysis was used to detect RAR-beta2 expression.Results: Cell lines SK-BR-3, T-47D, ZR-75-1, and MCF7 exhibited expression of RAR-beta2 only after demethylation and treatment with ATRA. The first exon expressed in the RAR-beta2 transcript was methylated in cell lines ZR-75-1 and SK-BR-3. Six breast cancer specimens showed methylation in the same region of the gene. No expression of RAR-beta2 was found in any grade III lesion. An inverse association between methylation and gene expression was found in all grade II lesions. The RAR-beta2 gene from non-neoplastic breast tissue was unmethylated and expressed.Conclusions: Methylation of the RAR-beta2 gene may be an initial step in breast carcinogenesis; treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality. [ABSTRACT FROM AUTHOR]

Aims Rotablation is a widely used technique for the treatment of complex coronary artery lesions but is so far only poorly supported by controlled studies. The Comparison of Balloon-Angioplasty versus Rotational Atherectomy study (COBRA) is a multicentre, prospective, randomized trial to compare short- and long-term effects of percutaneous transluminal coronary angioplasty (PTCA) and rotablation in patients with angiographically pre-defined complex coronary artery lesions.Methods and Results At seven clinical sites 502 patients with pre-defined complex coronary artery lesions were assigned to either PTCA (n=250) or rotablation (n=252). Primary end-points were procedural success, 6-month restenosis rates in the treated segments, and major cardiac events during follow-up. Procedural success was achieved in 78% (PTCA), and 85% (rotablation) (P=0·038) of cases. Crossover from PTCA to rotablation was 4% and 10% vice versa (P=0·019). There was no difference between PTCA and rotablation with respect to procedure-related complications such as Q wave infarctions (2·4% each), emergency bypass surgery (1·2% versus 2·4%), and death (1·6% versus 0·4%). However, more stents were required after PTCA (14·9% versus 6·4%, P<0·002), predominantely for bailout or unsatisfactory results. Including bail out stents as an end-point, the procedural success rates were 73% for angioplasty and 84% for rotablation (P=0·006). At 6 months, symptomatic outcome, target vessel reinterventions and restenosis rates (PTCA 51% versus rotablation 49%, P=0·33) were not different.Conclusion Complex coronary artery lesions can be treated with a high level of success and low complication rates either by PTCA with adjunctive stenting or rotablation. The long-term clinical and angiographic outcome is comparable. [ABSTRACT FROM PUBLISHER]

In this paper, reference priors are derived for three cases where partial information is available. If a subjective conditional prior is given, two reasonable methods are proposed for finding the marginal reference prior. If, instead, a subjective marginal prior is available, a method for defining the conditional reference prior is proposed. A sufficient condition is then given under which this conditional reference prior agrees with the conditional reference prior derived in the first stage of the reference prior algorithm of Berger & Bernardo (1989, 1992). Finally, under the assumption of independence, a method for finding marginal reference priors is also proposed. Various examples are given to illustrate the methods. [ABSTRACT FROM AUTHOR]

Background: Total-body irradiation, followed by hematopoietic system rescue by bone marrow transplantation (BMT), has been found to improve the response of patients with multiple myeloma to treatment with melphalan. The problems of nonhematopoietic toxicity from whole-body irradiation might be circumvented by using a bone-seeking radiopharmaceutical, such as samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP), to ablate the bone marrow.Purpose: A mouse model system for multiple myeloma was used to evaluate the potential therapeutic efficacy of sequential therapy with 153Sm-EDTMP, melphalan, and BMT.Methods: Female C57BL/KaLwRij mice were inoculated with 8 x 10(5) 5T33 murine myeloma cells. Treatment protocols were begun 3 or 10 days later, when the myeloma was either confined to bone marrow or disseminated in liver, spleen, and lymph nodes, simulating human multiple myeloma. 153Sm, a potent beta particle-emitting radioisotope of short half-life (46.7 hours), was linked to the bone-seeking chelate EDTMP. Animals in the first treatment group were each given 22.5 MBq 153Sm-EDTMP via the jugular vein (day 3 or 10), followed by 18.5 mg/kg melphalan (maximum tolerated dose) given intraperitoneally 5 days later (day 8 or 15) and syngeneic BMT another 2 days later (day 10 or 17). Survival in groups of six to 10 animals for each time series was compared with that in mice left untreated (control cohort), in mice treated with 153Sm-EDTMP alone (day 3 or 10), or in mice treated with melphalan alone (day 8 or 15). The hematopoietic systems of animals in the latter two treatment groups recovered full function, obviating the necessity of BMT. The end point was onset of paraparesis, at which time the animals were immediately killed by carbon dioxide asphyxiation.Results: Median survival in untreated control animals was 23 days in those with localized disease and 24 days in those with disseminated myeloma. Treatment with 153Sm-EDTMP alone improved survival to a median of 29 days when commenced on day 3 and 30 days when begun on day 10. Melphalan treatment alone improved the median survival to 31 days for animals with localized myeloma and 34 days in animals with disseminated disease. Additional improvement in survival to a median of 42 days was achieved in animals treated 3 days after tumor inoculation with sequential 153Sm-EDTMP, melphalan, and BMT; median survival was 40 days using this regimen in animals with disseminated myeloma.Conclusions: Animals in all three treatment protocols survived longer than those left untreated after inoculation with myeloma cells (P < .001). Sequential treatment with 153Sm-EDTMP, melphalan, and BMT was significantly more effective than single-agent treatment (P < .01). No evidence of radiotoxicity was detected in nonhematopoietic organs.Implications: The survival advantage conferred by our sequential treatment protocol suggests its potential clinical usefulness in the treatment of multiple myeloma and other hematologic malignancies in humans. [ABSTRACT FROM AUTHOR]

The efficacy and safety of amikacin were evaluated in 42 patients with infections presumed to be due to gram-negative rods. The dosage of 7.5 mg of amikacinjkg every 12 hr was administered intramuscularly to 32 patients and intravenously to seven patients; three patients with renal impairment were given a modified regimen. The duration of treatment was three to 51 days (mean, 9.6 days). Of 19 patients with acute pyelonephritis, five had positive blood culture results. Ten patients had chronic urinary infection, and isolates of Pseudomonas aeruginosa from four of these patients acquired resistance to amikacin during therapy. Of seven patients with gram-negative bacteremia from sources other than the urinary tract, four showed satisfactory and three had less than optimal responses to therapy with amikacin. Two patients with chronic osteomyelitis or soft tissue infection improved but subsequently relapsed. Two patients with acute febrile illness, in whom the etiologic agent was unidentified, recovered. Serial audiograms revealed no change in 26 of 27 patients; one had a significant deterioration in hearing. A transient rise in the level of serum creatinine was noted in three patients. Serial tests of liver function revealed no abnormalities. [ABSTRACT FROM PUBLISHER]

Purpose. Changes in glycosylated hemoglobin (HbA1c) levels, blood pressure measurements, and utilization metrics among diabetic patients managed by a clinical pharmacist were studied. Summary. This pharmacist intervention model was developed by Polk County, Florida, to engage patients with diabetes in managing their health based on the Asheville Project's framework. The diabetes program was implemented in February 2005, with an onsite clinical pharmacist to counsel participants with diabetes. The onsite pharmacist individualized each patient's care. After the initial assessment, educational deficiencies were noted and addressed as needed. Outcomes measured included changes in HbA1c, blood glucose, and blood pressure values and utilization metrics, such as hospitalization and emergency room visit rates, from baseline to one year after pharmacist intervention. Of the 564 participants who enrolled in the program, 477 were enrolled at the end of one year and were included in the analysis. Results showed that HbA1c values steadily decreased over the one-year study period. At baseline, there were 55% of participants with an average HbA1c value of <=7%. After one year, 72% of participants had HbA1c values of <=7%. Participants' mean systolic and diastolic blood pressure values were lower at the end of one year compared with the baseline. Participants also had a 30% reduction in hospital admissions, and the number of emergency room visits during the one-year period decreased by 24%. Conclusion. An employer-based pharmacist intervention model for patients with diabetes improved HbA1c levels, reduced systolic and diastolic blood pressure values, and decreased hospitalizations and emergency room visits after one year. [ABSTRACT FROM AUTHOR]