The correlations between the spin frequencies and kHz QPOs of Neutron Stars in LMXBs

We studied the correlations between spin frequencies and kilohertz quasi-periodic oscillations (kHz QPOs) in neutron star low mass X-ray binaries. The updated data of kHz QPOs and spin frequencies are statistically analyzed. We found that when two simultaneous kHz QPOs are present in the power spectrum, the minimum frequency of upper kHz QPO is at least 1.3 times larger than the spin frequency, i.e. \nu_{s}<\nu_{2min}/1.3. We also found that the average kHz QPO peak separation in 6 Atoll sources anti-correlates with the spin frequency in the form \lan\dn\ran = -(0.19\pm0.05)\ns+(389.40\pm21.67)Hz. If we shifted this correlation in the direction of the peak separation by a factor of 1.5, this correlation matches the data points of the two accretion powered millisecond X-ray pulsars, SAX J1808.4-3658 and XTE J1807-294.Comment: 4 pages, 2 figures, accepted for publication in A&

Timing properties and spectral states in Aquila X-1

We have analyzed five X-ray outbursts of the neutron-star soft X-ray transient Aql X-1 and investigated the timing properties of the source in correlation with its spectral states as defined by different positions in the color-color and hardness-intensity diagrams. The hard color and the source count rate serve as the distinguishing parameters giving rise to three spectral states: a low-intensity hard state, an intermediate state and a high-intensity soft state. These states are respectively identified with the extreme island, island and banana states that characterize the atoll sources. The large amount of data analyzed allowed us to perform for the first time a detailed timing analysis of the extreme island state. Differences in the aperiodic variability between the rise and the decay of the X-ray outbursts are found in this state: at the same place in the color-color diagram, during the rise the source exhibits more power at low frequencies (< 1 Hz), whereas during the decay the source is more variable at high frequencies (> 100 Hz). The very-low frequency noise that characterizes the banana-state power spectra below 1 Hz cannot be described in terms of a single power law but a two-component model is required. In two outbursts a new 6-10 Hz QPO has been discovered and tentatively identified with the normal/flaring branch-like oscillation observed only at the highest inferred mass accretion rates. We have compared the spectral and timing properties of Aql X-1 with those of other atoll and Z sources. Our results argue against a unification scheme for these two types of neutron-star X-ray binaries.Comment: 24 pages, 4 tables, 9 figures, accepted for publication in Ap

UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study

The aim of the study was to investigate the associations between UGT1A1*28 genotype and (1) response rates, (2) febrile neutropenia and (3) dose intensity in patients with metastatic colorectal cancer treated with irinotecan. UGT1A1*28 genotype was determined in 218 patients receiving irinotecan (either first-line therapy with capecitabine or second-line as monotherapy) for metastatic colorectal cancer. TA7 homozygotes receiving irinotecan combination therapy had a higher incidence of febrile neutropenia (18.2%) compared to the other genotypes (TA6/TA6 : 1.5%; TA6/TA7 : 6.5%, P=0.031). TA7 heterozygotes receiving irinotecan monotherapy also suffered more febrile neutropenia (19.4%) compared to TA6/TA6 genotype (2.2%; P=0.015). Response rates among genotypes were not different for both regimens: combination regimen, P=0.537; single-agent, P=0.595. TA7 homozygotes did not receive a lower median irinotecan dose, number of cycles (P-values ⩾0.25) or more frequent dose reductions compared to the other genotypes (P-values for trend; combination therapy: 0.62 and single-agent: 0.45). Reductions were mainly (>80%) owing to grade ⩾3 diarrhoea, not (febrile) neutropenia. TA7/TA7 patients have a higher incidence of febrile neutropenia upon irinotecan treatment, but were able to receive similar dose and number of cycles compared to other genotypes. Response rates were not significantly different

Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting

Mean glucose during ICU admission is related to mortality by a U-shaped curve in surgical and medical patients: a retrospective cohort study

Lowering of hyperglycemia in the intensive care unit (ICU) is widely practiced. We investigated in which way glucose regulation, defined as mean glucose concentration during admission, is associated with ICU mortality in a medical and a surgical cohort. Retrospective database cohort study including patients admitted between January 2004 and December 2007 in a 20-bed medical/surgical ICU in a teaching hospital. Hyperglycemia was treated using a computerized algorithm targeting for glucose levels of 4.0-7.0 mmol/l. Five thousand eight hundred twenty-eight patients were eligible for analyses, of whom 1,339 patients had a medical and 4,489 had a surgical admission diagnosis. The cohorts were subdivided in quintiles of increasing mean glucose. We examined the relation between these mean glucose strata and mortality. In both cohorts we observed the highest mortality in the lowest and highest strata. Logistic regression analysis adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, admission duration and occurrence of severe hypoglycemia showed that in the medical cohort mean glucose levels 8.4 mmol/l and in the surgical cohort mean glucose levels 9.4 mmol/l were associated with significantly increased ICU mortality (OR 2.4-3.0 and 4.9-6.2, respectively). Limitations of the study were its retrospective design and possible incomplete correction for severity of disease. Mean overall glucose during ICU admission is related to mortality by a U-shaped curve in medical and surgical patients. In this cohort of patients a 'safe range' of mean glucose regulation might be defined approximately between 7.0 and 9.0 mmol/

Relations Between Timing Features and Colors in the X-Ray Binary 4U 0614+09

We study the correlations between timing and X-ray spectral properties in the low mass X-ray binary 4U 0614+09 using a large (265-ks) data set obtained with the Rossi X-ray Timing Explorer. We find strong quasi-periodic oscillations (QPOs) of the X-ray flux, like the kilohertz QPOs in many other X-ray binaries with accreting neutron stars, with frequencies ranging from 1329 Hz down to 418 Hz and, perhaps, as low as 153 Hz. We report the highest frequency QPO yet from any low mass X-ray binary at 1329+-4 Hz, which has implications for neutron star structure. This QPO has a 3.5-sigma single-trial significance, for an estimated 40 trials the significance is 2.4-sigma. Besides the kilohertz QPOs, the Fourier power spectra show four additional components: high frequency noise (HFN), described by a broken power-law with a break frequency between 0.7 and 45 Hz, very low frequency noise (VLFN), which is fitted as a power-law below 1 Hz, and two broad Lorentzians with centroid frequencies varying from 6 to 38 Hz and 97 to 158 Hz, respectively. We find strong correlations between the frequencies of the kilohertz QPOs, the frequency of the 6 to 38 Hz broad Lorentzian, the break frequency of the HFN, the strength of both the HFN and the VLFN and the position of the source in the hard X-ray color vs. intensity diagram. The frequency of the 97 to 158 Hz Lorentzian does not correlate with these parameters. We also find that the relation between power density and break frequency of the HFN is similar to that established for black hole candidates in the low state. We suggest that the changing mass accretion rate is responsible for the correlated changes in all these parameters.Comment: ApJ, referee

A Method to Exchange Recombinant Differentially Phosphorylated Rhodamine-Labeled Cardiac RLC into Permeabilized Cardiac Trabeculae

Cyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs are characterized by narrow therapeutic windows, highly variable pharmacokinetics (PK), and metabolism by CYP3A enzymes. Recently, the decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated the effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on cyclosporine, everolimus, and tacrolimus PK in renal transplant patients. CYP3A4*22 carriers showed a significant lower clearance for cyclosporine (−15%), and a trend was observed for everolimus (−7%) and tacrolimus (−16%). Patients carrying at least one CYP3A5*1 allele had 1.5-fold higher tacrolimus clearance compared with noncarriers; however, CYP3A5*3 appeared to be nonpredictive for everolimus and cyclosporine. CYP3A combined genotype did not significantly improve prediction of clearance compared with CYP3A5*3 or CYP3A4*22 alone. These data suggest that dose individualization of cyclosporine, everolimus, or tacrolimus therapy based on CYP3A4*22 is not indicated

Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study

Objectives: In cerebral small vessel disease, whitematter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. Methods: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/ pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. Results: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (b=20.61; p=0.043), and worse compound scores for speed and motor control (b=20.25; p=0.006), executive functions (b=20.19; p=0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/ pallidum and the memory compound Z score (b=20.13; p=0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. Conclusion: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH