632 research outputs found
Many-body interactions and melting of colloidal crystals
We study the melting behavior of charged colloidal crystals, using a
simulation technique that combines a continuous mean-field Poisson-Boltzmann
description for the microscopic electrolyte ions with a Brownian-dynamics
simulation for the mesoscopic colloids. This technique ensures that many-body
interactions between the colloids are fully taken into account, and thus allows
us to investigate how many-body interactions affect the solid-liquid phase
behavior of charged colloids. Using the Lindemann criterion, we determine the
melting line in a phase-diagram spanned by the colloidal charge and the salt
concentration. We compare our results to predictions based on the established
description of colloidal suspensions in terms of pairwise additive Yukawa
potentials, and find good agreement at high-salt, but not at low-salt
concentration. Analyzing the effective pair-interaction between two colloids in
a crystalline environment, we demonstrate that the difference in the melting
behavior observed at low salt is due to many-body interactions
Predictors of transitioning to adult mental health services and associated costs: a cross-country comparison
BACKGROUND: Young people are at risk of falling through the care gap after leaving child and adolescent mental health services (CAMHS) despite an ongoing need for mental health support. Currently, little is known about the predictors of transitioning to adult mental health services (AMHS), and associated healthcare and societal costs as young people cross the transition boundary. OBJECTIVE: To conduct a secondary data analysis exploring predictors of transitioning or falling through the gap and associated costs. METHODS: Data were used from a longitudinal study, which followed young people from seven European countries for 2âyears after reaching their CAMHS boundary. Predictors of transitioning (including sociodemographic and clinical variables) and longitudinal resource use were compared for 488 young people who transitioned to AMHS versus those who fell through the gap. FINDINGS: Young people were more likely to transition to AMHS if they were severely ill. Those from Italy, the Netherlands and the UK were more likely to fall through the gap than transition to AMHS. Healthcare costs fell for all young people over the study, with a sharper decrease for those who fell through the gap. CONCLUSIONS: Total healthcare costs fell for all participants, indicating that the intensity of mental health support reduces for all young people as they cross the CAMHS boundary, regardless of clinical need. CLINICAL IMPLICATIONS: It is important that alternative forms of mental health support are available for young people who do not meet the AMHS care threshold but still have mental health needs after leaving CAMHS
Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma
Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes.Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-MĂŒllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls.Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation.All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score.Conclusion: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.</p
The osmotic pressure of charged colloidal suspensions: A unified approach to linearized Poisson-Boltzmann theory
We study theoretically the osmotic pressure of a suspension of charged
objects (e.g., colloids, polyelectrolytes, clay platelets, etc.) dialyzed
against an electrolyte solution using the cell model and linear
Poisson-Boltzmann (PB) theory. From the volume derivative of the grand
potential functional of linear theory we obtain two novel expressions for the
osmotic pressure in terms of the potential- or ion-profiles, neither of which
coincides with the expression known from nonlinear PB theory, namely, the
density of microions at the cell boundary. We show that the range of validity
of linearization depends strongly on the linearization point and proof that
expansion about the selfconsistently determined average potential is optimal in
several respects. For instance, screening inside the suspension is
automatically described by the actual ionic strength, resulting in the correct
asymptotics at high colloid concentration. Together with the analytical
solution of the linear PB equation for cell models of arbitrary dimension and
electrolyte composition explicit and very general formulas for the osmotic
pressure ensue. A comparison with nonlinear PB theory is provided. Our analysis
also shows that whether or not linear theory predicts a phase separation
depends crucially on the precise definition of the pressure, showing that an
improper choice could predict an artificial phase separation in systems as
important as DNA in physiological salt solution.Comment: 16 pages, 5 figures, REVTeX4 styl
Electronic reminders for pathologists promote recognition of patients at risk for Lynch syndrome: cluster-randomised controlled trial
We investigated success factors for the introduction of a guideline on recognition of Lynch syndrome in patients recently diagnosed with colorectal cancer (CRC) below age 50 or a second CRC below age 70. Pathologists were asked to start microsatellite instability (MSI) testing and report to surgeons with the advice to consider genetic counselling when MSI test or family history was positive. A multicentre cluster-randomised controlled trial (ClinicalTrials.gov, number NCT00141466) was performed in 12 pathology laboratories (clusters), serving 29 community hospitals. All received an introduction to the new guideline. In the intervention group, surgeons received education and tumour test result reminders; pathologists were provided with inclusion criteria cards, an electronic patient inclusion reminder system and feedback on inclusion. Two hundred sixty-six CRC patients were eligible for recognition as at risk for Lynch syndrome. The actual recognition was 18% more successful in the intervention as compared to the control arm (77% (120 of 156) compared to 59% (65 of 110)), with an adjusted odds ratio (OR)â=â2.8 (95% confidence interval (CI) 1.1â7.0). The electronic reminder system for pathologists was most strongly associated with recognition of high-risk patients, ORâ=â4.2 (95% CI 1.7â10.1). An electronic reminder system for pathologists appeared effective for adherence to a new complex guideline and will enhance the recognition of Lynch syndrome
International external validation of a stratification tool to identify branch-duct intraductal papillary mucinous neoplasms at lowest risk of progression
BACKGROUND: Identifying branchâduct intraductal papillary mucinous neoplasms (BDâIPMNs) at lowest risk of progression may allow for a reduced intensity of surveillance. OBJECTIVE: We aimed to externally validate the previously developed DutchâAmerican Risk stratification Tool (DARTâ1; https://rtools.mayo.edu/DART/), which identifies cysts at low risk of developing worrisome features (WFs) or highârisk stigmata (HRS). METHODS: Three prospective cohorts of individuals under surveillance for BDâIPMNs were combined, independent from the original development cohort. We assessed the performance (discrimination and calibration) of DARTâ1, a multivariable Coxâproportional logistic regression model with five predictors for the development of WFs or HRS. RESULTS: Of 832 individuals (mean age 77 years, SD 11.5) under surveillance for a median of 40 months (IQR 44), 163 (20%) developed WFs or HRS. DARTâ1's discriminative ability (Câstatistic 0.68) was similar to that in the development cohort (0.64â0.72) and showed moderate calibration. DARTâ1 adequately estimated the risk for patients in the middle risk quintile, and slightly underestimated it in the lowest quintiles. Their range of predicted versus observed 3âyear risk was 0%â0% versus 0%â3.7% for Q1; 0.3%â0.4% versus 3%â11% for Q2; and 2.6%â3% versus 2.4%â9.8% for Q3. The development of WFs or HRS was associated with pancreatic cancer (p < 0.001). Vice versa, in absence of WFs or HRS, the risk of malignancy was low (0.3%). CONCLUSIONS: The performance of DARTâ1 to predict the development of WFs or HRS in BDâIPMN was validated in an external international cohort, with a discriminative ability equal as in the development cohort. Risk estimations were most accurate for patients with BDâIPMNs in the middle risk quintile and slightly underestimated in the lowest quintiles
Impacts of organic and conventional crop management on diversity and activity of free-living nitrogen fixing bacteria and total bacteria are subsidiary to temporal effects
A three year field study (2007-2009) of the diversity and numbers of the total and metabolically active free-living diazotophic bacteria and total bacterial communities in organic and conventionally managed agricultural soil was conducted at the Nafferton Factorial Systems Comparison (NFSC) study, in northeast England. The result demonstrated that there was no consistent effect of either organic or conventional soil management across the three years on the diversity or quantity of either diazotrophic or total bacterial communities. However, ordination analyses carried out on data from each individual year showed that factors associated with the different fertility management measures including availability of nitrogen species, organic carbon and pH, did exert significant effects on the structure of both diazotrophic and total bacterial communities. It appeared that the dominant drivers of qualitative and quantitative changes in both communities were annual and seasonal effects. Moreover, regression analyses showed activity of both communities was significantly affected by soil temperature and climatic conditions. The diazotrophic community showed no significant change in diversity across the three years, however, the total bacterial community significantly increased in diversity year on year. Diversity was always greatest during March for both diazotrophic and total bacterial communities. Quantitative analyses using qPCR of each community indicated that metabolically active diazotrophs were highest in year 1 but the population significantly declined in year 2 before recovering somewhat in the final year. The total bacterial population in contrast increased significantly each year. Seasonal effects were less consistent in this quantitative study
Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologistâs initiative
According to the Dutch Guideline on Hereditary Colorectal Cancer published in 2008, patients with recently diagnosed colorectal cancer (CRC) should undergo microsatellite instability (MSI) testing by a pathologist immediately after tumour resection if they are younger than 50 years, or if a second CRC has been diagnosed before the age of 70 years, owing to the high risk of Lynch syndrome (MIPA). The aim of the present MIPAPS study was to investigate general distress and cancer-specific distress following MSI testing. From March 2007 to September 2009, 400 patients who had been tested for MSI after newly diagnosed CRC were recruited from 30 Dutch hospitals. Levels of general distress (SCL-90) and cancer-specific distress (IES) were assessed immediately after MSI result disclosure (T1) and 6 months later (T2). Response rates were 23/77 (30%) in the MSI-positive patients and 58/323 (18%) in the MSI-negative patients. Levels of general distress and cancer-specific distress were moderate. In the MSI-positive group, 27% of the patients had high general distress at T1 versus 18% at T2 (p = 0.5), whereas in the MSI-negative group, these percentage were 14 and 18% (p = 0.6), respectively. At T1 and T2, cancer-specific distress rates in the MSI-positive group and MSI-negative group were 39 versus 27% (p = 0.3) and 38 versus 36% (p = 1.0), respectively. High levels of general distress were correlated with female gender, low social support and high perceived cancer risk. Moderate levels of distress were observed after MSI testing, similar to those found in other patients diagnosed with CRC. Immediately after result disclosure, high cancer-specific distress was observed in 40% of the MSI-positive patients
Pharmacokinetic boosting of olaparib:A randomised, cross-over study (PROACTIVE-study)
Background: Pharmacokinetic (PK) boosting is the intentional use of a drug-drug interaction to enhance systemic drug exposure. PK boosting of olaparib, a CYP3A-substrate, has the potential to reduce PK variability and financial burden. The aim of this study was to investigate equivalence of a boosted, reduced dose of olaparib compared to the non-boosted standard dose. Methods: This cross-over, multicentre trial compared olaparib 300 mg twice daily (BID) with olaparib 100 mg BID boosted with the strong CYP3A-inhibitor cobicistat 150 mg BID. Patients were randomised to the standard therapy followed by the boosted therapy, or vice versa. After seven days of each therapy, dense PK sampling was performed for noncompartmental PK analysis. Equivalence was defined as a 90% Confidence Interval (CI) of the geometric mean ratio (GMR) of the boosted versus standard therapy area under the plasma concentration-time curve (AUC0â12 h) within no-effect boundaries. These boundaries were set at 0.57â1.25, based on previous pharmacokinetic studies with olaparib capsules and tablets. Results: Of 15 included patients, 12 were eligible for PK analysis. The GMR of the AUC0â12 h was 1.45 (90% CI 1.27â1.65). No grade â„3 adverse events were reported during the study. Conclusions: Boosting a 100 mg BID olaparib dose with cobicistat increases olaparib exposure 1.45-fold, compared to the standard dose of 300 mg BID. Equivalence of the boosted olaparib was thus not established. Boosting remains a promising strategy to reduce the olaparib dose as cobicistat increases olaparib exposure Adequate tolerability of the boosted therapy with higher exposure should be established.</p
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