370 research outputs found
Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.
Interpolated wave functions for nonadiabatic simulations with the fixed-node quantum Monte Carlo method
Simulating nonadiabatic effects with many-body wave function approaches is an
open field with many challenges. Recent interest has been driven by new
algorithmic developments and improved theoretical understanding of properties
unique to electron-ion wave functions. Fixed-node diffusion Monte Caro is one
technique that has shown promising results for simulating electron-ion systems.
In particular, we focus on the CH molecule for which previous results suggested
a relatively significant contribution to the energy from nonadiabatic effects.
We propose a new wave function ansatz for diatomic systems which involves
interpolating the determinant coefficients calculated from configuration
interaction methods. We find this to be an improvement beyond previous wave
function forms that have been considered. The calculated nonadiabatic
contribution to the energy in the CH molecule is reduced compared to our
previous results, but still remains the largest among the molecules under
consideration.Comment: 7 pages, 3 figure
Cohesive properties of alkali halides
We calculate cohesive properties of LiF, NaF, KF, LiCl, NaCl, and KCl with
ab-initio quantum chemical methods. The coupled-cluster approach is used to
correct the Hartree-Fock crystal results for correlations and to systematically
improve cohesive energies, lattice constants and bulk moduli. After inclusion
of correlations, we recover 95-98 % of the total cohesive energies. The lattice
constants deviate from experiment by at most 1.1 %, bulk moduli by at most 8 %.
We also find good agreement for spectroscopic properties of the corresponding
diatomic molecules.Comment: LaTeX, 10 pages, 1 figure, accepted by Phys. Rev.
Hematologic Safety of Radium-223 Dichloride: Baseline Prognostic Factors Associated With Myelosuppression in the ALSYMPCA Trial.
BACKGROUND: Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity. PATIENTS AND METHODS: Hematologic parameters and adverse events were analyzed. Multivariate analyses assessing baseline risk factors for hematologic toxicities were performed separately for radium-223 and placebo patients. RESULTS: Nine hundred one patients received radium-223 (n = 600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus placebo patients (6% vs. 2%). Logistic regression analyses identified significant baseline predictors for grade 2-4 hematologic toxicities related to radium-223 treatment: extent of disease (6-20 vs. < 6 bone metastases; odds ratio [OR] = 2.76; P = .022) and elevated prostate-specific antigen (OR = 1.65; P = .006) for anemia; prior docetaxel (OR = 2.16; P = .035), decreased hemoglobin (OR = 1.35; P = .008), and decreased platelets (OR = 1.44; P = .030) for thrombocytopenia. Neutropenia events were too few in placebo patients for a comparative analysis. There were no significant associations between hematologic toxicities and number of radium-223 injections received (4-6 vs. 1-3). CONCLUSION: Radium-223 has a favorable safety profile with a low myelosuppression incidence. Understanding baseline factors associated with myelosuppression may assist clinicians in avoiding severe myelosuppression events with radium-223
Assessing Perceived Risk and STI Prevention Behavior: A National Population-Based Study with Special Reference to HPV
Aim: This thesis aims to provide a multidimensional assessment of infection risks and
to evaluate strategies for HPV prevention including vaccination with quadrivalent HPVvaccines,
dose-level vaccine effectiveness and condom use in high STI risk situations.
Methods: Multiple population-based registers and questionnaire responses provided data
for this thesis. Various multivariable and univariate regression models were fit.
Findings: Overall, quadrivalent HPV-vaccination was highly effective against genital
warts (GW) also referred to as condyloma, which is the first HPV disease endpoint
possible to measure. However, effectiveness was contingent upon young age-at-first
vaccination, with effectiveness declining steadily the older the age-at-first vaccination.
Among women above 20 years of age there was low to immeasurable effectiveness and
suggestive evidence vaccinations in this age group tended to reach women at high GW
risk. There were marked socioeconomic disparities in the opportunistic (on-demand with
co-pay) vaccination strategy evaluated, with women and girls who have parents with
the highest education level compared to the lowest having a 15 times greater likelihood
to be vaccinated (Study III). Once vaccination was initiated, however, high parental
education level was unrelated to vaccination completion. Maximum protection against
GW was found among girls vaccinated under the age of 17 who had received three doses
of the vaccine. No differences in effectiveness were found for girls who received twodoses
between ages 10-16 with that of those who received three-doses between ages 17-
19 (Study IV). GW affects more men than women in Sweden as of 2010 with 453 per
100 000 men and 365 per 100 000 women treated. A decline between 25-30% was seen
between 2006 and 2010 among women in the age groups with the highest vaccination
coverage. No decline was found amongst men and their GW incidence has steadily
increased between 2006 and 2010 (Study II). Reported condom use in high risk situations
was low among both men and women, with 41% of men and 34% of women reporting
always/almost always condom use with temporary partners. STI risk perception was also
low, with approximately 10% of sexually active respondents considering themselves at
large risk of contracting an STI. There was no association between men’s condom use and
their STI risk perception but there was an association for women (Study I).
Conclusions: Results suggest that males bear a substantial burden of HPV-related
condyloma where incidence has dropped among women. When planning HPVvaccination
among females, efforts should target girls under age 14 for maximum
effectiveness. Quadrivalent HPV-vaccination offers most protection against condyloma at
three doses. Gross social inequity was found with opportunistic HPV-vaccination. There
were large gender differences in factors associated with condom use in high risk situations
and STI risk perceptions
Trends in non-metastatic prostate cancer management in the Northern and Yorkshire region of England, 2000–2006
Background:
Our objective was to analyse variation in non-metastatic prostate cancer management in the Northern and Yorkshire region of England.
Methods:
We included 21 334 men aged ⩾55, diagnosed between 2000 and 2006. Principal treatment received was categorised into radical prostatectomy (11%), brachytherapy (2%), external beam radiotherapy (16%), hormone therapy (42%) and no treatment (29%).
Results:
The odds ratio (OR) for receiving a radical prostatectomy was 1.53 in 2006 compared with 2000 (95% CI 1.26–1.86), whereas the OR for receiving hormone therapy was 0.57 (0.51–0.64). Age was strongly associated with treatment received; radical treatments were significantly less likely in men aged ⩾75 compared with men aged 55–64 years, whereas the odds of receiving hormone therapy or no treatment were significantly higher in the older age group. The OR for receiving radical prostatectomy, brachytherapy or external beam radiotherapy were all significantly lower in the most deprived areas when compared with the most affluent (0.64 (0.55–0.75), 0.32 (0.22–0.47) and 0.83 (0.74–0.94), respectively) whereas the OR for receiving hormone therapy was 1.56 (1.42–1.71).
Conclusions:
This study highlights the variation and inequalities that exist in the management of non-metastatic prostate cancer in the Northern and Yorkshire region of England
Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial
<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (<sup>125</sup>I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with <sup>125</sup>I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during <sup>125</sup>I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p
Theoretical investigation of the electronic structure of Fe(II) complexes at spin-state transitions
The electronic structure relevant to low spin (LS)high spin (HS) transitions in Fe(II) coordination compounds with a FeN6 core are studied. The selected [Fe(tz)6]2+(1) (tz=1H-tetrazole), [Fe(bipy)3]2+(2) (bipy=2,2’-bipyridine) and [Fe(terpy)2]2+ (3) (terpy=2,2’:6’,2’’-terpyridine) complexes have been actively studied experimentally, and with their respective mono-, bi-, and tridentate ligands, they constitute a comprehensive set for theoretical case studies. The methods in this work include density functional theory (DFT), time-dependent DFT (TD-DFT) and multiconfigurational second order perturbation theory (CASPT2). We determine the structural parameters as well as the energy splitting of the LS-HS states (ΔEHL) applying the above methods, and comparing their performance. We also determine the potential energy curves representing the ground and low-energy excited singlet, triplet, and quintet d6 states along the mode(s) that connect the LS and HS states. The results indicate that while DFT is well suited for the prediction of structural parameters, an accurate multiconfigurational approach is essential for the quantitative determination of ΔEHL. In addition, a good qualitative agreement is found between the TD-DFT and CASPT2 potential energy curves. Although the TD-DFT results might differ in some respect (in our case, we found a discrepancy at the triplet states), our results suggest that this approach, with due care, is very promising as an alternative for the very expensive CASPT2 method. Finally, the two dimensional (2D) potential energy surfaces above the plane spanned by the two relevant configuration coordinates in [Fe(terpy)2]2+ were computed both at the DFT and CASPT2 levels. These 2D surfaces indicate that the singlet-triplet and triplet-quintet states are separated along different coordinates, i.e. different vibration modes. Our results confirm that in contrast to the case of complexes with mono- and bidentate ligands, the singlet-quintet transitions in [Fe(terpy)2]2+ cannot be described using a single configuration coordinate
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