Search

Purpose: Breast cancer follow-up (surveillance and aftercare) varies from one-size-fits-all to more personalised approaches. A systematic review was performed to get insight in existing evidence on (cost-)effectiveness of personalised follow-up. Methods: PubMed, Scopus and Cochrane were searched between 01–01-2010 and 10–10-2022 (review registered in PROSPERO:CRD42022375770). The inclusion population comprised nonmetastatic breast cancer patients ≥ 18 years, after completing curative treatment. All intervention-control studies studying personalised surveillance and/or aftercare designed for use during the entire follow-up period were included. All review processes including risk of bias assessment were performed by two reviewers. Characteristics of included studies were described. Results: Overall, 3708 publications were identified, 64 full-text publications were read and 16 were included for data extraction. One study evaluated personalised surveillance. Various personalised aftercare interventions and outcomes were studied. Most common elements included in personalised aftercare plans were treatment summaries (75%), follow-up guidelines (56%), lists of available supportive care resources (38%) and PROs (25%). Control conditions mostly comprised usual care. Four out of seven (57%) studies reported improvements in quality of life following personalisation. Six studies (38%) found no personalisation effect, for multiple outcomes assessed (e.g. distress, satisfaction). One (6.3%) study was judged as low, four (25%) as high risk of bias and 11 (68.8%) as with concerns. Conclusion: The included studies varied in interventions, measurement instruments and outcomes, making it impossible to draw conclusions on the effectiveness of personalised follow-up. There is a need for a definition of both personalised surveillance and aftercare, whereafter outcomes can be measured according to uniform standards. [ABSTRACT FROM AUTHOR]

The renewed interest in the relationship between the Gospel of Mark and the apostle Paul has led to more nuanced arguments for Paul's influence on Mark based on refined methodologies. In this article, I critically evaluate the current state of the argument, concluding that it depends on too many variables and expects too much of our sparse evidence to make a convincing argument that Mark is distinctly Pauline. Therefore, the Gospel of Mark should be read independently of Paul so that its unique features might be first understood within its own narrative world, rather than interpreted through a Pauline lens. [ABSTRACT FROM AUTHOR]

This article critically evaluates the meanings of "within Judaism" and related phrases when applied to the texts now collected in the New Testament. It uses social-scientific approaches to social categories and group boundaries to develop a theoretically informed approach for considering how the literature of the earliest Christ followers may or may not be considered Jewish texts, and how such claims can be evaluated. Examples from New Testament and Early Jewish texts illustrate the theoretical discussion throughout. [ABSTRACT FROM AUTHOR]

Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy. The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak. Sixty recommendations were provided for suspected allergy to β-lactam antibiotics (BLAs) and non–β-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team. Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non–β-lactam antibiotics, thereby strongly supporting antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

In the last 60 years, the proportion of white Americans expressing anti-black prejudice in face-to-face survey interviews has declined dramatically. To test whether social desirability pressures affect the expression of anti-black prejudice, we analyzed a within-subjects experiment in the 2008 American National Election Study in which white respondents first reported their endorsement of stereotypes of blacks confidentially via audio computer-assisted self-interviewing (ACASI) and weeks or months later orally during second interviews. Shifting to ACASI led to a small but significant increase in negative views of blacks. Unexpectedly, shifting to ACASI also led to a similarly large increase in negative views of whites. Furthermore, the ACASI reports had no more predictive validity than did the oral reports. This evidence suggests that social desirability pressures do not seriously compromise oral reports of racial stereotypes in face-to-face interviews. [ABSTRACT FROM AUTHOR]

Large scale quantum calculations for molar enthalpy of formation (Δf H0), standard entropy (S0), and heat capacity (CV) are presented. A large data set may help to evaluate quantum thermochemistry tools in order to uncover possible hidden shortcomings and also to find experimental data that might need to be reinvestigated, indeed we list and annotate approximately 200 problematic thermochemistry measurements. Quantum methods systematically underestimate S0 for flexible molecules in the gas phase if only a single (minimum energy) conformation is taken into account. This problem can be tackled in principle by performing thermochemistry calculations for all stable conformations [Zheng et al., Phys. Chem. Chem. Phys. 13, 10885-10907 (2011)], but this is not practical for large molecules. We observe that the deviation of composite quantum thermochemistry recipes from experimental S0 corresponds roughly to the Boltzmann equation (S = R lnΩ), where R is the gas constant and Ω the number of possible conformations. This allows an empirical correction of the calculated entropy for molecules with multiple conformations. With the correction we find an RMSD from experiment of ≋13 J/mol K for 1273 compounds. This paper also provides predictions of Δf H0, S0, and CV for well over 700 compounds for which no experimental data could be found in the literature. Finally, in order to facilitate the analysis of thermodynamics properties by others we have implemented a new tool obthermo in the OpenBabel program suite [O'Boyle et al., J. Cheminf. 3, 33 (2011)] including a table of reference atomization energy values for popular thermochemistry methods. [ABSTRACT FROM AUTHOR]

This nationwide study provides an overview of trends and variations in radiotherapy use as part of multimodal treatment of invasive non-metastatic breast cancer in the Netherlands in 2008–2019. Women with invasive non-metastatic breast cancer were selected from the population-based Netherlands Cancer Registry. Treatments trends were presented over time. Factors associated with (1) boost irradiation in breast-conserving therapy and (2) regional radiotherapy instead of axillary lymph node dissection (ALND) in N+ disease were identified using multilevel logistic regression analyses. Radiotherapy use increased from 61% (2008) to 70% (2016), caused by breast-conserving therapy instead of mastectomy, increased post-mastectomy radiotherapy, and increased regional radiotherapy (32% in 2011 to 61% in 2019) instead of ALND in N+ disease. Omission of radiotherapy after breast-conserving surgery (BCS) in 2016–2019 (4–9%, respectively), mainly in elderly, decreased overall radiotherapy use to 67%. Radiotherapy treatment was further de-escalated by decreased boost irradiation in breast-conserving therapy (66% in 2011 to 37% in 2019) and partial (1% in 2011 to 6% in 2019) instead of whole breast irradiation following BCS. Boost irradiation was associated with high-risk features: younger age (OR>75 vs <50:0.04, 95%CI:0.03–0.05), higher grade (OR grade III vs I:11.46, 95%CI:9.90–13.26) and residual disease (OR focal residual vs R0-resection:28.08, 95%CI:23.07–34.17). Variation across the country was found for both boost irradiation use (OR South vs North:0.58, 95%CI:0.49–0.68), and regional radiotherapy instead of ALND (OR Southwest vs North:0.55, 95%CI:0.37–0.80). Overall radiotherapy use increased in 2008–2016, while a decreasing trend was observed after 2016, caused by post-BCS radiotherapy omission. Boost irradiation in breast-conserving therapy became omitted in low-risk patients, and regional radiotherapy use increased as an alternative for ALND in N+ disease. • Overall radiotherapy (RT) use in M0 breast cancer increased in 2008–2016 (61–70%). • Thereafter, RT use decreased to 67% (2019) because of post-BCS RT omission in elderly. • Breast-conserving therapy: boost use decreased, partial breast irradiation increased. • Low-risk patients less likely received boost irradiation in breast-conserving therapy. • Regional RT was increasingly used as alternative for ALND in nodal disease. [ABSTRACT FROM AUTHOR]

Disbalances in the adaptive and humoral immune system may cause IgG4-related disease. This rare disease can affect multiple organ systems, including the retroperitoneum. Retroperitoneal fibrosis can result in postrenal obstruction with accompanied renal failure and/or pain. By means of two case presentations we want to draw attention to this rare disease entity and share our experiences regarding favorable treatment responses with rituximab after unsuccessful treatment with prednisolone. [ABSTRACT FROM AUTHOR]

Cox Proportional Hazards (CPH) analysis is the standard for survival analysis in oncology. Recently, several machine learning (ML) techniques have been adapted for this task. Although they have shown to yield results at least as good as classical methods, they are often disregarded because of their lack of transparency and little to no explainability, which are key for their adoption in clinical settings. In this paper, we used data from the Netherlands Cancer Registry of 36,658 non-metastatic breast cancer patients to compare the performance of CPH with ML techniques (Random Survival Forests, Survival Support Vector Machines, and Extreme Gradient Boosting [XGB]) in predicting survival using the c -index. We demonstrated that in our dataset, ML-based models can perform at least as good as the classical CPH regression (c -index ∼ 0.63 ), and in the case of XGB even better (c -index ∼ 0.73 ). Furthermore, we used Shapley Additive Explanation (SHAP) values to explain the models' predictions. We concluded that the difference in performance can be attributed to XGB's ability to model nonlinearities and complex interactions. We also investigated the impact of specific features on the models' predictions as well as their corresponding insights. Lastly, we showed that explainable ML can generate explicit knowledge of how models make their predictions, which is crucial in increasing the trust and adoption of innovative ML techniques in oncology and healthcare overall. [ABSTRACT FROM AUTHOR]

Cox Proportional Hazards (CPH) analysis is the standard for survival analysis in oncology. Recently, several machine learning (ML) techniques have been adapted for this task. Although they have shown to yield results at least as good as classical methods, they are often disregarded because of their lack of transparency and little to no explainability, which are key for their adoption in clinical settings. In this paper, we used data from the Netherlands Cancer Registry of 36,658 non-metastatic breast cancer patients to compare the performance of CPH with ML techniques (Random Survival Forests, Survival Support Vector Machines, and Extreme Gradient Boosting [XGB]) in predicting survival using the c -index. We demonstrated that in our dataset, ML-based models can perform at least as good as the classical CPH regression (c -index ∼ 0.63 ), and in the case of XGB even better (c -index ∼ 0.73 ). Furthermore, we used Shapley Additive Explanation (SHAP) values to explain the models' predictions. We concluded that the difference in performance can be attributed to XGB's ability to model nonlinearities and complex interactions. We also investigated the impact of specific features on the models' predictions as well as their corresponding insights. Lastly, we showed that explainable ML can generate explicit knowledge of how models make their predictions, which is crucial in increasing the trust and adoption of innovative ML techniques in oncology and healthcare overall. [ABSTRACT FROM AUTHOR]

Previous studies have discovered a somewhat paradoxical empirical pattern whereby members of some higher educated first- and second-generation migrant groups in the Netherlands, who are structurally better integrated, harbour more negative attitudes toward natives than their lower educated counterparts, a.k.a. 'the integration paradox'. This finding goes against intergroup contact theory which predicts that the greater contact with natives among highly educated migrants should improve their attitudes toward natives. Here we ask whether this negative relationship between education and attitudes toward natives can already be observed at an earlier stage in the lives of immigrants, in adolescence. In survey data on Dutch first- and second-generation immigrant adolescents, we find no integration paradox: Instead, education positively predicts attitudes toward natives. This positive relationship can largely be attributed to the greater opportunity for befriending native peers in higher educational tracks, which in turn produces more favourable attitudes toward natives, consistent with contact theory. We conclude that if the integration paradox is a robust phenomenon in adulthood, it is either restricted to migrants who do not grow up in the Netherlands, or the attitudes of immigrants radically change after they finish high school. [ABSTRACT FROM AUTHOR]

Purpose: Propensity trimming, hierarchical modelling and instrumental variable (IV) analysis are statistical techniques dealing with confounding, cluster-related variation or confounding by severity. This study aimed to explain (dis)advantages of these techniques in estimating the effect of breast-conserving therapy (BCT) and mastectomy on 10-year distant metastasis-free survival (DMFS). Methods: All women diagnosed in 2005 with primary T1-2N0-1 breast cancer treated with BCT or mastectomy were selected from the Netherlands Cancer Registry. We used multivariable Cox regression to correct for confounding. Propensity trimming was used to create a more homogeneous population for which the treatment choice was not self-evident. Hospital of surgery was used as hierarchical level to handle hospital-related variation, and as IV to deal with unmeasured confounding. Results: Multivariable Cox regression showed higher 10-year DMFS for BCT than mastectomy [HR 0.70 (95% CI 0.60–82)]. Propensity trimming on the 10–90th and the 20–80th percentile of the propensity score distribution and hierarchical modelling showed similar HRs. IV analysis showed no significant difference between BCT and mastectomy. Conclusion: Unmeasured confounding is very difficult to eliminate in observational research. We cannot conclude that BCT or mastectomy has a causal relationship with 10-year DMFS. It is crucial to critically evaluate all model's assumptions, and to be careful in drawing firm conclusions. [ABSTRACT FROM AUTHOR]

Presents long molecular dynamics simulations of water using popular water models. Dependence of properties on the system size; Impact of the cut-off treatment on density, energy, dynamic, and dielectric properties; Generation of two special-purpose water model.

We describe a generalizable approach to the development of phase transferable effective intermolecular potentials and apply the method to the study of N2. The method is based on a polarizable shell model description of the isolated molecule and uses experimental data to establish the parameters. Consideration of the Ne dimer shows this to be a conceptual advance over point polarizability descriptions of atomic interaction. Our parametrization of N2 accurately describes not only the molecule’s electrostatic field (i.e., a practical representation of the molecular charge distribution) but also its response to electrical and mechanical stress (polarization and deformation). The purely intermolecular terms in our potential reflect shell-shell interactions. These are parametrized by fitting properties of the low temperature solid phase of nitrogen. We derive a phase transferable potential able to account for the second virial coefficient of the gas phase, the pressure induced phase transition between nitrogen’s cubic and tetragonal phases, and a wide range of liquid properties (pair distribution function, heat of vaporization, self-diffusion coefficient and dielectric constant). © 1995 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Reports on the deposition mechanism involved in photochemical vapor deposition of tungsten (W) of gallium arsenide. Examination of the temperature dependence of the deposition rate; Properties of W; Details of the procedure of the deposition experiments.

Examines the deposition of tungsten (W) in gallium arsenide through hydrogen formed without the use of laser. Details of the experimental techniques used; Information on a commonly used activation technique for W chemical vapor deposition; Overview of maximum W coverages obtained after a deposition time of ten minutes.

Objective: Many cancer survivors are facing difficulties in getting a life insurance; raised premiums and declinatures are common. We generated a prediction model estimating the conditional extra mortality risk of breast cancer patients in the Netherlands. This model can be used by life insurers to accurately estimate the additional risk of an individual patient, conditional on the years survived. Methodology: All women diagnosed with stage I-III breast cancer in 2005–2006, treated with surgery, were selected from the Netherlands Cancer Registry. For all stages separately, multivariable logistic regression was used to estimate annual mortality risks, conditional on the years survived, until 10 years after diagnosis, resulting in 30 models. The conditional extra mortality risk was calculated by subtracting mortality rates of the general Dutch population from the patient mortality rates, matched by age, gender and year. The final model was internally and externally validated, and tested by life insurers. Results: We included 23,234 patients: 10,101 stage I, 9,868 stage II and 3,265 stage III. The final models included age, tumor stage, nodal stage, lateralization, location within the breast, grade, multifocality, hormonal receptor status, HER2 status, type of surgery, axillary lymph node dissection, radiotherapy, (neo)adjuvant systemic therapy and targeted therapy. All models showed good calibration and discrimination. Testing of the model by life insurers showed that insurability using the newly-developed model increased with 13%, ranging from 0%-24% among subgroups. Conclusion: The final model provides accurate conditional extra mortality risks of breast cancer patients, which can be used by life insurers to make more reliable calculations. The model is expected to increase breast cancer patients’ insurability and transparency among life insurers. [ABSTRACT FROM AUTHOR]

Background: Landmark trials have shown breast‐conserving surgery (BCS) combined with radiotherapy to be as safe as mastectomy in breast cancer treatment. This population‐based study aimed to evaluate trends in BCS from 1989 to 2015 in nine geographical regions in the Netherlands. Methods: All women diagnosed between 1989 and 2015 with primary T1–2 N0–1 breast cancer, treated with BCS or mastectomy, were identified from the Netherlands Cancer Registry. Crude and case mix‐adjusted rates of BCS were evaluated and compared between nine Dutch regions for two time intervals: 1989–2002 and 2003–2015. The annual percentage change in BCS per region over time was assessed by means of Joinpoint regression analyses. Explanatory variables associated with the choice of initial surgery were evaluated using multivariable logistic regression. Results: A total of 202 934 patients were included, 82 200 treated in 1989–2002 and 120 734 in 2003–2015. During 1989–2002, the mean rate of BCS was 50·6 per cent, varying significantly from 39·0 to 71·7 per cent between the nine regions. For most regions, a marked rise in BCS was observed between 2002 and 2003. During 2003–2015, the mean rate of BCS increased to 67·4 per cent, but still varied significantly between regions from 58·5 to 75·5 per cent. A significant variation remained after case‐mix correction. Conclusion: This large nationwide study showed that the use of BCS increased from 1989 to 2015 in the Netherlands. After adjustment for explanatory variables, a large variation still existed between the nine regions. This regional variation underlines the need for implementation of a uniform treatment and decision‐making strategy. Regional differences remain [ABSTRACT FROM AUTHOR]

Abstract Background Survival estimates from diagnosis are of limited importance for (ex-)breast cancer patients who survived several years, as it includes information on already deceased patients. This study analysed the 10-year conditional risk of recurrent breast cancer in specific prognostic subgroups. Second, we investigated 10-year conditional overall survival (OS) and relative survival (RS), adjusted for confounding. Patients and methods All women diagnosed in 2005 with operated T1-2N0-1 breast cancer were selected from the Netherlands Cancer Registry. Patients were classified into T1N0, T1N1, T2N0 and T2N1 stage. Ten-year conditional recurrence rates were calculated from diagnosis, and for patients without an event (local [LR], regional recurrence [RR], distant metastasis [DM] or death) every year following diagnosis. Ten-year conditional OS was calculated using multivariable Cox regression. RS was estimated by dividing patient survival rates by those of the general Dutch population. Results We included 7969 patients: 52.3% had T1N0, 15.3% T1N1, 19.9% T2N0 and 12.5% T2N1 stage. For T1N0, 10-year LR rates changed from 4.6% at diagnosis to 0.5% in year 10. RR rates changed from 2.3% to 0.2%, and DM rates changed from 7.8% to 0.6%. For T2N1 stage, the LR, RR and DM rates changed from 6.2% to 0.8%, 5.2%–0.4% and 19.6%–1.5%, respectively. For the luminal A subtype, LR, RR and DM rates changed from 3.9% to 0.4%, 1.7%–0.5% and 7.3%–1.1%, while for triple negative, these rates changed from 5.6% to 0.7%, 4.9%–0.2% and 16.7%–0%, respectively. Differences between subgroups attenuated over time, and all recurrence rates became ≤1.5% in year 10. Ten-year OS and RS, adjusted for confounding, showed declining risk differences between subgroups over time. Conclusion Differences in recurrence rates, OS and RS between prognostic subgroups declined as years passed by. These results highlight the importance of taking into account disease-free years to more accurately predict (ex-)breast cancer patients' prognosis over time. Highlights • Survival estimates from diagnosis are less important for breast cancer survivors. • Conditional survival includes the numbers of years survived following diagnosis. • Differences in recurrence risks between prognostic subgroups declined over time. • Differences in overall and relative survival between subgroups declined as well. • Conditional survival and recurrences provide patients better insight in prognosis. [ABSTRACT FROM AUTHOR]

Background The incidence of ductal carcinoma in situ (DCIS) has drastically increased over the past decades. Because DCIS is resected after diagnosis similar to invasive breast cancer, the natural cause and behaviour of DCIS is not well known. We aimed to determine breast cancer–specific survival (BCSS) and overall survival (OS) according to grade in DCIS patients after surgical treatment in the Netherlands. Patients and methods All DCIS patients diagnosed between 1999 and 2012 were selected from the Netherlands Cancer Registry. The cause of death was obtained from ‘Statistics Netherlands’. BCSS and OS were estimated using multivariable Cox regression in the entire cohort and stratified for grades. Results In total, 12,256 patients were included, of whom 1509 (12.3%) presented with grade I, 3675 (30.0%) with grade II, 6064 (49.5%) with grade III and 1008 (8.2%) with an unknown grade. During a median follow-up of 7.8 years, 1138 (9.3%) deaths were observed, and 179 (1.5%) were breast cancer–related. Of these, 10 patients had grade I; 46 grade II; 95 grade III and 28 an unknown grade. After adjustment for confounding, grade II and III were related to worse BCSS than grade I with hazard ratios of 1.92 (95% confidence interval [CI]: 0.97–3.81) and 2.14 (95% CI: 1.11–4.12), respectively. No association between grades and OS was observed. Conclusion BCSS and OS in DCIS patients were excellent. Because superior rates were observed for low-grade DCIS, it seems justified to investigate whether active surveillance may be a balanced alternative for conventional surgical treatment. [ABSTRACT FROM AUTHOR]

Background PREDICT version 2.0 is increasingly used to estimate prognosis in breast cancer. This study aimed to validate this tool in specific prognostic subgroups in the Netherlands. Methods All operated women with non-metastatic primary invasive breast cancer, diagnosed in 2005, were selected from the nationwide Netherlands Cancer Registry (NCR). Predicted and observed 5- and 10-year overall survival (OS) were compared for the overall cohort, separated by oestrogen receptor (ER) status, and predefined subgroups. A >5% difference was considered as clinically relevant. Discriminatory accuracy and goodness-of-fit were determined using the area under the receiver operating characteristic curve (AUC) and the Chi-squared-test. Results We included 8834 patients. Discriminatory accuracy for 5-year OS was good (AUC 0.80). For ER-positive and ER-negative patients, AUCs were 0.79 and 0.75, respectively. Predicted 5-year OS differed from observed by −1.4% in the entire cohort, −0.7% in ER-positive and −4.9% in ER-negative patients. Five-year OS was accurately predicted in all subgroups. Discriminatory accuracy for 10-year OS was good (AUC 0.78). For ER-positive and ER-negative patients AUCs were 0.78 and 0.76, respectively. Predicted 10-year OS differed from observed by −1.0% in the entire cohort, −0.1% in ER-positive and −5.3 in ER-negative patients. Ten-year OS was overestimated (6.3%) in patients ≥75 years and underestimated (−13.%) in T3 tumours and patients treated with both endocrine therapy and chemotherapy (−6.6%). Conclusions PREDICT predicts OS reliably in most Dutch breast cancer patients, although results for both 5-year and 10-year OS should be interpreted carefully in ER-negative patients. Furthermore, 10-year OS should be interpreted cautiously in patients ≥75 years, T3 tumours and in patients considering endocrine therapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Background:The Dutch guidelines advise to start radiation therapy (RT) within 5 weeks following breast-conserving surgery (BCS). However, much controversy exists regarding timing of RT. This study investigated its effect on 10-year disease-free survival (DFS) in a Dutch population-based cohort.Methods:All women diagnosed with primary invasive stage I-IIIA breast cancer in 2003 treated with BCS+RT were included. Two populations were studied. Population 1 excluded patients receiving chemotherapy before RT. Analyses were stratified for use of adjuvant systemic therapy (AST). Population 2 included patients treated with chemotherapy, and compared chemotherapy before (BCS-chemotherapy-RT) and after RT (BCS-RT-chemotherapy). DFS was estimated using multivariable Cox regression. Locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were secondary outcomes.Results:Population 1 (n=2759) showed better DFS and DMFS for a time interval of >55 than a time interval of <42 days. Patients treated with AST showed higher DFS for >55 days (hazards ratio (HR) 0.60 (95% confidence interval (CI): 0.38-0.94)) and 42-55 days (HR 0.64 (95% CI: 0.45-0.91)) than <42 days. Results were similar for DMFS, while timing did not affect LRRFS and OS. For patients without AST, timing was not associated with DFS, DMFS and LLRFS, but 10-year OS was significantly lower for 42-55 and >55 days compared to <42 days. In population 2 (n=1120), timing did not affect survival in BCS-chemotherapy-RT. In BCS-RT-chemotherapy, DMFS was higher for >55 than <42 days.Conclusions:Starting RT shortly after BCS seems not to be associated with a better long-term outcome. The common position that RT should start as soon as possible following surgery in order to increase treatment efficacy can be questioned. [ABSTRACT FROM AUTHOR]

Background: Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer.Methods: In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1-2, N0-1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data.Findings: Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 [95% CI 0·49-0·53]; p<0·0001; adjusted HR 0·81 [0·78-0·85]; p<0·0001), and this improvement remained significant for all subgroups of different T and N stages of breast cancer. After adjustment for confounding variables, breast-conserving surgery plus radiotherapy did not significantly improve 10 year distant metastasis-free survival in the 2003 cohort overall compared with mastectomy (adjusted HR 0·88 [0·77-1·01]; p=0·07), but did in the T1N0 subgroup (adjusted 0·74 [0·58-0·94]; p=0·014). Breast-conserving surgery plus radiotherapy did significantly improve 10 year relative survival in the 2003 cohort overall (adjusted 0·76 [0·64-0·91]; p=0·003) and in the T1N0 subgroup (adjusted 0·60 [0·42-0·85]; p=0·004) compared with mastectomy.Interpretation: Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer.Funding: None. [ABSTRACT FROM AUTHOR]

The harmonic angle bending potential is used in many force fields for (bio)molecular simulation. The force associated with this potential is discontinuous at angles close to 180°, which can lead to numeric instabilities. Angle bending of linear groups, such as alkynes or nitriles, or linear molecules, such as carbon dioxide, can be treated by a simple harmonic potential if we describe the fluctuations as a deviation from a reference position of the central atom, the position of which is determined by the flanking atoms. The force constant for the linear angle potential can be derived analytically from the corresponding force constant in the traditional potential. The new potential is tested on the properties of alkynes, nitriles, and carbon dioxide. We find that the angles of the linear groups remain about 2° closer to 180° using the new potential. The bond and angle force constants for carbon dioxide were tuned to reproduce the experimentally determined frequencies. An interesting finding was that simulations of liquid carbon dioxide under pressure with the new flexible model were stable only when explicitly modeling the long-range Lennard-Jones (LJ) interactions due to the very long-range nature of the LJ interactions (>1.7 nm). In the other tested liquids, we find that a Lennard-Jones cutoff of 1.1 nm yields similar results as the particle mesh Ewald algorithm for LJ interactions. Algorithmic factors influencing the stability of liquid simulations are discussed as well. Finally, we demonstrate that the linear angle potential can be used in free energy perturbation calculations. [ABSTRACT FROM AUTHOR]

Background: Follow-up of curatively treated primary breast cancer patients consists of surveillance and aftercare and is currently mostly the same for all patients. A more personalized approach, based on patients' individual risk of recurrence and personal needs and preferences, may reduce patient burden and reduce (healthcare) costs. The NABOR study will examine the (cost-)effectiveness of personalized surveillance (PSP) and personalized aftercare plans (PAP) on patient-reported cancer worry, self-rated and overall quality of life and (cost-)effectiveness. Methods: A prospective multicenter multiple interrupted time series (MITs) design is being used. In this design, 10 participating hospitals will be observed for a period of eighteen months, while they -stepwise- will transit from care as usual to PSPs and PAPs. The PSP contains decisions on the surveillance trajectory based on individual risks and needs, assessed with the 'Breast Cancer Surveillance Decision Aid' including the INFLUENCE prediction tool. The PAP contains decisions on the aftercare trajectory based on individual needs and preferences and available care resources, which decision-making is supported by a patient decision aid. Patients are non-metastasized female primary breast cancer patients (N = 1040) who are curatively treated and start follow-up care. Patient reported outcomes will be measured at five points in time during two years of follow-up care (starting about one year after treatment and every six months thereafter). In addition, data on diagnostics and hospital visits from patients' Electronical Health Records (EHR) will be gathered. Primary outcomes are patient-reported cancer worry (Cancer Worry Scale) and overall quality of life (as assessed with EQ-VAS score). Secondary outcomes include health care costs and resource use, health-related quality of life (as measured with EQ5D-5L/SF-12/EORTC-QLQ-C30), risk perception, shared decision-making, patient satisfaction, societal participation, and cost-effectiveness. Next, the uptake and appreciation of personalized plans and patients' experiences of their decision-making process will be evaluated. Discussion: This study will contribute to insight in the (cost-)effectiveness of personalized follow-up care and contributes to development of uniform evidence-based guidelines, stimulating sustainable implementation of personalized surveillance and aftercare plans. Trial registration: Study sponsor: ZonMw. Retrospectively registered at ClinicalTrials.gov (2023), ID: NCT05975437. [ABSTRACT FROM AUTHOR]

Abstract: Background: The Body Image Concern Inventory (BICI), the Whitely Index (WI), and the Checklist Individual Strength (CIS-20R) are three questionnaires often incorporated in routine outcome monitoring (ROM). Respectively, they assess symptom severity in patients with body dysmorphic disorder, hypochondriasis, and chronic fatigue syndrome. We aimed to generate reference values for a healthy population and for a population of patients fulfilling diagnostic criteria for at least one of BDD, hypochondriasis, and CFS, treated in specialized mental health care. Methods: The healthy ROM reference-group (n=648) was recruited through general practitioners. These subjects were matched for age and sex with the ROM patient-group (n=823). To define limits (i.e., cut-off-values) for one-sided reference intervals (5th percentile [P 5] for ROM patient-group and 95th percentile [P 95] for ROM reference-group) the outermost 5% of observations were used. Discriminative powers were evaluated by receiver operating characteristics (ROC) analyses Results: Cut-off-values (P 95 ROM reference-group) were 55 for the BICI, 6 for the WI, and 92 for the CIS-20R. These values differed for men and women, being mostly higher for women. The discriminative power of all three somatoform questionnaires was very high. Limitations: Substantial non-response and limited generalizability. Conclusions: For the BICI, WI, and CIS-20R a comprehensive set of reference values was obtained. The reference values may support clinical decisions regarding adjusting or terminating therapy, and possible referral. [Copyright &y& Elsevier]

Abstract: Background: The monitoring of patients with an anxiety disorder can benefit from Routine Outcome Monitoring (ROM). As anxiety disorders differ in phenomenology, several anxiety questionnaires are included in ROM: Brief Scale for Anxiety (BSA), PADUA Inventory Revised (PI-R), Panic Appraisal Inventory (PAI), Penn State Worry Questionnaire (PSWQ), Worry Domains Questionnaire (WDQ), Social Interaction, Anxiety Scale (SIAS), Social Phobia Scale (SPS), and the Impact of Event Scale-Revised (IES-R). We aimed to generate reference values for both ‘healthy’ and ‘clinically anxious’ populations for these anxiety questionnaires. Methods: We included 1295 subjects from the general population (ROM reference-group) and 5066 psychiatric outpatients diagnosed with a specific anxiety disorder (ROM patient-group). The MINI was used as diagnostic device in both the ROM reference group and the ROM patient group. To define limits for one-sided reference intervals (95th percentile; P 95) the outermost 5% of observations were used. Receiver Operating Characteristics (ROC) analyses were used to yield alternative cut-off values for the anxiety questionnaires. Results: For the ROM reference-group the mean age was 40.3 years (SD=12.6), and for the ROM patient-group it was 36.5 years (SD=11.9). Females constituted 62.8% of the reference-group and 64.4% of the patient-group. P 95 ROM reference group cut-off values for reference versus clinically anxious populations were 11 for the BSA, 43 for the PI-R, 37 for the PAI Anticipated Panic, 47 for the PAI Perceived Consequences, 65 for the PAI Perceived Self-efficacy, 66 for the PSWQ, 74 for the WDQ, 32 for the SIAS, 19 for the SPS, and 36 for IES-R. ROC analyses yielded slightly lower reference values. The discriminative power of all eight anxiety questionnaires was very high. Limitations: Substantial non-response and limited generalizability. Conclusions: For eight anxiety questionnaires a comprehensive set of reference values was provided. Reference values were generally higher in women than in men, implying the use of gender-specific cut-off values. Each instrument can be offered to every patient with MAS disorders to make responsible decisions about continuing, changing or terminating therapy. [Copyright &y& Elsevier]

Abstract: Background: The Beck Depression Inventory-II (BDI-II), the Inventory of Depressive Symptoms (self-report) (IDS-SR) and the Montgomery-Äsberg Depression Rating Scale (MADRS) are questionnaires that assess symptom severity in patients with a depressive disorder, often part of Routine Outcome Monitoring (ROM). We aimed to generate reference values for both “healthy” and “clinically depressed” populations. Methods: We included 1295 subjects from the general population (ROM reference-group) recruited through general practitioners, and 4627 psychiatric outpatients diagnosed with Major Depressive Disorder (MDD) or dysthymia (ROM patient-group). The outermost 5% of observations were used to define limits for one-sided reference intervals (95th percentiles; P95). Receiver Operating Characteristics (ROC) analyses were used to yield alternative cut-off values. Internal consistency was assessed. Results: The mean age was 40.3yr (SD=12.6) and 39.3 (SD=12.3) for the ROM reference and patient-groups, respectively, and 62.8% versus 61.0% were female. Cut-off (P95) values differed for women and men, being respectively 15 and 12 for the BDI-II, 23 and 18 for the IDS-SR, and 12.5 and 9 for the MADRS. ROC analyses yielded almost equal reference values. The discriminative power of the BDI-II, IDS-SR and MADRS scores was very high. Internal consistency was excellent for total scores and satisfactory for all subscales, except for the IDS-SR subscale Atypical Characteristics. Limitations: Substantial non-response and limited generalizability. Conclusions: For the BDI-II, IDS-SR and MADRS a comprehensive set of reference values were provided. Reference values were higher in women than in men, implying the use of sex-specific cut-off values. Either instrument can be offered to every patient with MAS disorders to make responsible decisions about continuing, changing or terminating therapy. [Copyright &y& Elsevier]

Rationale, aims and objectives: Routine outcome monitoring (ROM) was developed to establish the outcome of psychotherapeutic and pharmacological treatments through repeated assessments before, during and after treatment. Although standardization of psychiatric assessments and their reference values are essential for patient care, for various ROM instruments reference values are not available. The aim of the Leiden ROM Study is to generate reference values for 22 ROM instruments, covering generic and specific mood, anxiety and somatoform (MAS) disorders, for the general population. This article describes the extensive process of recruitment, as well as baseline characteristics of patient versus non-patient groups. Method: Cross-sectional study in randomly selected participants aged 18-65 years from the Dutch population, included through general practitioners. Results: Extensive demographic, psychosocial, mental health, and biological data from 1302 participants, recruited via general practitioners, were collected during a two-hour standardized assessment including observer-rated and self-report scales. These data will be compared with corresponding data from 7840 patients with psychopathology who were referred to secondary care. On-going quality control and calibration ensured maintenance of high quality during data collection. Conclusions: This reference group study for mental health assessments is the first study of this size carried out in the Netherlands. The results of this study are expected to be of value to secondary psychiatric care because they allow the indication of progress in health, treatment effect and possible termination of treatment. Additionally, the reference values can be used by primary care physicians as decision threshold for referral to specialized mental health care and vice versa. [ABSTRACT FROM AUTHOR]

Abstract: Self-report measures of psychological distress or psychopathology are widely used and can be easily implemented as psychiatric screening tools. Positive psychological constructs such as vitality/optimism and work functioning have scarcely been incorporated. We aimed to develop and validate a psychological distress instrument, including measures of vitality and work functioning. A patient sample with suspected depressive, anxiety, and somatoform disorders (N=242) and a reference sample of the general population (N=516) filled in the 48-item Symptom Questionnaire (SQ-48) plus a battery of observer-rated and self-report scales (MINI Plus, MADR, BAS, INH, BSI), using a web-based ROM programme. The resulting SQ-48 is multidimensional and includes the following nine subscales: Depression (MOOD, six items), Anxiety (ANXI, six items), Somatization (SOMA, seven items), Agoraphobia (AGOR, four items), Aggression (AGGR, four items), Cognitive problems (COGN, five items), Social Phobia (SOPH, five items), Work functioning (WORK, five items), and Vitality (VITA, six items). The results showed good internal consistency as well as good convergent and divergent validity. The SQ-48 is meant to be available in the public domain for Routine Outcome Monitoring (ROM) and can be used as a screening/ monitoring tool in clinical settings (psychiatric and non-psychiatric), as a benchmark tool, or for research purposes. [Copyright &y& Elsevier]

Introduction: The Brief Symptom Inventory (BSI), Mood & Anxiety Symptom Questionnaire ?30 (MASQ-D30), Short Form Health Survey 36 (SF-36), and Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) are generic instruments that can be used in Routine Outcome Monitoring (ROM) of patients with common mental disorders. We aimed to generate reference values usually encountered in 'healthy' and 'psychiatrically ill' populations to facilitate correct interpretation of ROM results. Methods: We included the following specific reference populations: 1294 subjects from the general population (ROM reference group) recruited through general practitioners, and 5269 psychiatric outpatients diagnosed with mood, anxiety, or somatoform (MAS) disorders (ROM patient group). The outermost 5% of observations were used to define limits for one-sided reference intervals (95th percentiles for BSI, MASQ-D30 and DAPP-SF, and 5th percentiles for SF-36 subscales). Internal consistency and Receiver Operating Characteristics (ROC) analyses were performed. Results: Mean age for the ROM reference group was 40.3 years (SD=12.6) and 37.7 years (SD=12.0) for the ROM patient group. The proportion of females was 62.8% and 64.6%, respectively. The mean for cut-off values of healthy individuals was 0.82 for the BSI subscales, 23 for the three MASQ-D30 subscales, 45 for the SF-36 subscales, and 3.1 for the DAPP-SF subscales. Discriminative power of the BSI, MASQ-D30 and SF-36 was good, but it was poor for the DAPP-SF. For all instruments, the internal consistency of the subscales ranged from adequate to excellent. Discussion and conclusion: Reference values for the clinical interpretation were provided for the BSI, MASQ-D30, SF-36, and DAPP-SF. Clinical information aided by ROM data may represent the best means to appraise the clinical state of psychiatric outpatients. [ABSTRACT FROM AUTHOR]

Background Lupinus angustifolius (blue lupine) is used for human and animal consumption. Currently, the lupine content in bread varies from 0% to 10% and from 0.5% to 3% in pastry. Although lupine flour is present in many products, anaphylaxis on lupine flour is rarely seen. Objective The aim of our study was to determine the clinical relevance of sensitization to lupine flour. Methods From October 2004 until October 2005, we performed skin prick tests (SPT) with lupine flour, peanut and soy extracts in consecutive patients attending our allergy clinic with a suspected food allergy. In patients sensitized to lupine flour, double-blind placebo-controlled food challenges (DBPCFC) were performed and specific IgE was measured. Results We tested 372 patients. SPTs with peanut, soy and lupine flour were positive in 135, 58 and 22 patients, respectively. Nine patients with sensitization to lupine flour underwent DBPCFC, which was negative in eight cases. In contrast, one patient experienced significant symptoms. Four of these nine patients suspected lupine by history. Two other patients with a positive history to lupine declined from challenges. In these patients, a 3-day dietary record showed that they could consume lupine without symptoms. Specific IgE in the serum was positive for L. angustifolius, peanut and soy in all nine patients. Conclusion These results demonstrate that clinical lupine allergy is very uncommon, even in the presence of sensitization to lupine flour. The estimated prevalence of lupine allergy, among patients with a suspected food allergy, referred to a tertiary allergy centre in the Netherlands is 0.27–0.81%. In most, although not all cases, sensitization is not clinically relevant and is most likely caused by cross-sensitization to peanut. In selected cases, eliciting doses are low, making significant reactions possible. Cite this as: N. W. de Jong, M. S. van Maaren, B. J. Vlieg-Boersta, A. E. J. Dubois, H. de Groot and R. Gerth van Wijk, Clinical & Experimental Allergy, 2010 (40) 1571–1577. [ABSTRACT FROM AUTHOR]

Abstract: We investigate the Semidefinite Programming based sums of squares (SOS) decomposition method, designed for global optimization of polynomials, in the context of the (Maximum) Satisfiability problem. To be specific, we examine the potential of this theory for providing tests for unsatisfiability and providing MAX-SAT upper bounds. We compare the SOS approach with existing upper bound and rounding techniques for the MAX-2-SAT case of Goemans and Williamson [Improved approximation algorithms for maximum cut and satisfiability problems using semidefinite programming, J. Assoc. Comput. Mach. 42(6) (1995) 1115–1145] and Feige and Goemans [Approximating the value of two prover proof systems, with applications to MAX2SAT and MAXDICUT, in: Proceedings of the Third Israel Symposium on Theory of Computing and Systems, 1995, pp. 182–189] and the MAX-3-SAT case of Karloff and Zwick [A 7/8-approximation algorithm for MAX 3SAT? in: Proceedings of the 38th Annual IEEE Symposium on Foundations of Computer Science, Miami Beach, FL, USA, IEEE Press, New York, 1997], which are based on Semidefinite Programming as well. We prove that for each of these algorithms there is an SOS-based counterpart which provides upper bounds at least as tight, but observably tighter in particular cases. Also, we propose a new randomized rounding technique based on the optimal solution of the SOS Semidefinite Program (SDP) which we experimentally compare with the appropriate existing rounding techniques. Further we investigate the implications to the decision variant SAT and compare experimental results with those yielded from the higher lifting approach of Anjos [On semidefinite programming relaxations for the satisfiability problem, Math. Methods Oper. Res. 60(3) (2004) 349–367; An improved semidefinite programming relaxation for the satisfiability problem, Math. Programming 102(3) (2005) 589–608; Semidefinite optimization approaches for satisfiability and maximum-satisfiability problems, J. Satisfiability Boolean Modeling Comput. 1 (2005) 1–47]. We give some impression of the fraction of the so-called unit constraints in the various SDP relaxations. From a mathematical viewpoint these constraints should be easily dealt within an algorithmic setting, but seem hard to be avoided as extra constraints in an SDP setting. Finally, we briefly indicate whether this work could have implications in finding counterexamples to uncovered cases in Hilbert''s Positivstellensatz. [Copyright &y& Elsevier]

The thermodynamics of hydrogen bond breaking and formation was studied in solutions of alcohol (methanol, ethanol, 1-propanol) molecules. An extensive series of over 400 molecular dynamics simulations with an aggregate length of over 900 ns was analyzed using an analysis technique in which hydrogen bond (HB) breaking is interpreted as an Eyring process, for which the Gibbs energy of activation ΔG‡ can be determined from the HB lifetime. By performing simulations at different temperatures, we were able to determine the enthalpy of activation ΔH‡ and the entropy of activation TΔS‡ for this process from the Van't Hoff relation. The equilibrium thermodynamics was determined separately, based on the number of donor hydrogens that are involved in hydrogen bonds. Results (ΔH) are compared to experimental data from Raman spectroscopy and found to be in good agreement for pure water and methanol. The ΔG as well as the ΔG‡ are smooth functions of the composition of the mixtures. The main result of the calculations is that ΔG is essentially independent of the environment (around 5 kJ/mol), suggesting that buried hydrogen bonds (e.g., in proteins) do not contribute significantly to protein stability. Enthalpically HB formation is a downhill process in all substances; however, for the alcohols there is an entropic barrier of 6−7 kJ/mol, at 298.15 K, which cannot be detected in pure water. [ABSTRACT FROM AUTHOR]

Egg hatch, larval growth, and metamorphosis of southern flounder, Paralichthys lethostigma, were examined at 13, 17, 21, and 25°C in laboratory experiments. The experiments were separated into four developmental phases: (1) from fertilization until hatch; (2) from hatch until mouth opening; (3) from first feeding until the onset of metamorphosis; (4) from the onset until the completion of metamorphosis. Time to egg hatch were 109, 58, 39, 30 hours at 13, 17, 21, and 25°C, respectively. Size at hatch varied little among temperatures, while percent hatch was significantly higher at 17°C (P < 0.05). There was no significant difference in total length at mouth opening among temperatures (P > 0.05). However, those larvae raised at higher temperatures reached mouth opening earlier, as it took on average 7.4, 3.9, 2.8, and 2.2 days from hatch at 13, 17, 21, and 25°C, respectively. During phase three, the growth rate was optimal at 17°C, as growth rates were 0.046, 0.110, 0.106 and 0.096 mm/day at 13, 17, 21, and 25°C, respectively. Larvae in phase four completed metamorphosis sooner at higher temperatures than at lower temperatures. It took 26.4, 15.7, and 13.1 days to complete metamorphosis at 17, 21, and 25°C, respectively, while only 16% of those at 13 progressed to stage “G” within the 27 days that phase four encompassed. No difference in total length was found among treatments (P > 0.05) at the completion of metamorphosis, but fish in the 21°C treatment had a significantly higher survival (P < 0.05). It can be concluded that southern flounder could be produced in the highest quantity and at the largest size by raising them at 17°C from fertilization until the onset of metamorphosis, and at 21°C during metamorphosis. [ABSTRACT FROM PUBLISHER]

Southern flounder (Paralichthys lethostigma) larvae were cultured at 17°C and observations were made to describe the morphological development from hatch until the completion of metamorphosis. A complete nine-part staging scheme was described with diagrams to show how larvae transform from a pelagic form with eyes on opposite sides of the body to a benthic form with both eyes on the left side of the body. The descriptions track the development of features that are easy to identify under low power microscopy. Behavioral patterns are included for each stage, particularly as they pertain to feeding. Such a staging scheme will help hatchery managers monitor development and confirm normal morphology and behavior. [ABSTRACT FROM PUBLISHER]

Background: Clinical prediction models are not routinely validated. To facilitate validation procedures, the online Evidencio platform ( https://www.evidencio.com ) has developed a tool partly automating this process. This study aims to determine whether semi-automated validation can reliably substitute manual validation.Methods: Four different models used in breast cancer care were selected: CancerMath, INFLUENCE, Predicted Probability of Axillary Metastasis, and PREDICT v.2.0. Data were obtained from the Netherlands Cancer Registry according to the inclusion criteria of the original development population. Calibration (intercepts and slopes) and discrimination (area under the curve (AUC)) were compared between semi-automated and manual validation.Results: Differences between intercepts and slopes of all models using semi-automated validation ranged from 0 to 0.03 from manual validation, which was not clinically relevant. AUCs were identical for both validation methods.Conclusions: This easy to use semi-automated validation option is a good substitute for manual validation and might increase the number of validations of prediction models used in clinical practice. In addition, the validation tool was considered to be user-friendly and to save a lot of time compared to manual validation. Semi-automated validation will contribute to more accurate outcome predictions and treatment recommendations in the target population. [ABSTRACT FROM AUTHOR]

Introduction: Prick‐to‐prick (PTP) test with fresh food is accepted as a reliable tool for measuring sensitization to fruits and vegetables. Not all fruits and vegetables are available throughout the year. The objective of this study was to investigate whether skin prick test (SPT) performed with frozen juice of fruits and vegetables (FJFV) is a good alternative to PTP tests performed with fresh fruits and vegetables (FFV). Methods: Adult patients suspected of having a food allergy to fruits and/or vegetables were included. A questionnaire was used to score symptoms after consumption of apple, kiwi, peach, tomato, and carrot. SPTs with FJFV, and PTP tests with FFV were performed. Intra‐class correlation coefficients (ICC) between the SPT and PTP test results were calculated. The sensitivity and specificity of both diagnostic tests towards food allergen specific symptoms (FASS) were calculated. Results: Thirty‐six patients were included. FASS was positive in 75% for apple, 53% for kiwi, 44% for peach, 25% for tomato, and 22% for carrot. ICC between SPT and PTP test results were moderate for apple (0.72) and kiwi (0.71), strong for peach (0.75) and tomato (0.89), and very strong for carrot (0.94). Sensitivity was equal for the SPT and PTP tests for apple (0.93), peach (0.81), and carrot (1.00), and comparable for kiwi (0.50 resp. 0.70), and tomato (0.44 resp. 0.56). Specificity was equal for apple (0.33), peach (0.15), and carrot (0.41), and comparable for kiwi (0.29 resp. 0.21) and tomato (0.80 resp. 0.72). Conclusions: Results of SPT with FJFV and PTP test with FFV are comparable. SPT with FJFV is a good alternative in the daily practice of the allergists. [ABSTRACT FROM AUTHOR]

We have studied mixtures of alcohol and water in an extensive series of 465 molecular-dynamics simulations with an aggregate length of 713 ns, in order to study excess properties of mixing, in particular the relation between mobility and viscosity. Methanol/water, ethanol/water, and 1-propanol/water mixtures were simulated using an alcohol content of 0–100 mass % in steps of 10%, using the OPLS (optimized potential for liquid simulations) force field for the alcohol molecules and the TIP4P (transferable intermolecular potential with four particles) water model. Computed densities and energies show very good agreement with experimental data for bulk simulations and the mixtures are satisfactory as well. The shear viscosity was computed using nonequilibrium molecular-dynamics simulations. Other properties studied include diffusion constants and rotational correlation times. We find the mobility to correlate well with the viscosity data, i.e., at intermediate alcohol concentrations the viscosity is maximal and the mobility is minimal. Furthermore, we have combined the viscosity and diffusion calculations in order to compute an effective hydrodynamic radius of the particles in the mixtures, using the Stokes–Einstein relation. This analysis indicates that there is no collective diffusion of molecular clusters in these mixtures. For all properties we find that the excess values are underestimated in the simulations, which, given that the pure liquids are described rather well, raises the question whether the potential function is too simplistic to describe mixtures quantitatively. The set of simulations presented here can hence be regarded as a force-field benchmark. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The faecal immunochemical test (FIT) is widely employed for colorectal cancer screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring haemoglobin, calprotectin, and serpin family F member 2, has demonstrated enhanced sensitivity for advanced neoplasia, especially advanced adenomas, at equal specificity to FIT. This study aimed to prospectively validate and investigate the clinical utlitity of mtFIT versus FIT in a setting of population-based colorectal cancer screening. Individuals aged 55–75 years and who were eligible for the Dutch national FIT-based colorectal cancer screening programme were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 μg/g haemoglobin cutoff) or mtFIT (based on decision-tree algorithm) led to a colonoscopy referral. The primary outcome was the relative detection rate of mtFIT versus FIT for all advanced neoplasia. Secondary outcomes were the relative detection rates of colorectal cancer, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on colorectal cancer incidence, mortality, and cost, determined with microsimulation modelling. The study has been registered in ClinicalTrials.gov , NCT05314309 , and is complete. Between March 25 and Dec 7, 2022, 35 786 individuals were invited to participate in the study, of whom 15 283 (42·7%) consented, and 13 187 (86·3%) of 15 283 provided both mtFIT and FIT samples with valid results. Of the 13 187 participants, 6637 (50·3%) were male and 6550 (49·7%) were female. mtFIT showed a 9·11% (95% CI 8·62–9·61) positivity rate and 2·27% (95% CI 2·02–2·54) detection rate for advanced neoplasia, compared with a positivity rate of 4·08% (3·75–4·43) and a detection rate of 1·21% (1·03–1·41) for FIT. Detection rates of mtFIT versus FIT were 0·20% (95% CI 0·13–0·29) versus 0·17% (0·11–0·27) for colorectal cancer; 1·64% (1·43–1·87) versus 0·86% (0·72–1·04) for advanced adenoma, and 0·43% (0·33–0·56) versus 0·17% (0·11–0·26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce colorectal cancer incidence by 21% and associated mortality by 18% compared with the current Dutch colorectal cancer screening programme, at feasible costs. Furthermore, at equal positivity rates, mtFIT outperformed FIT in terms of diagnostic yield. At an equally low positivity rate, mtFIT-based screening was predicted to further decrease colorectal cancer incidence by 5% and associated mortality by 4% compared with FIT-based screening. The higher detection rate of mtFIT for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer incidence and associated mortality reductions in programmatic colorectal cancer screening. Stand Up to Cancer, Dutch Cancer Society, Dutch Digestive Foundation, and Health~Holland. [ABSTRACT FROM AUTHOR]

Background: The Dutch guidelines advise to start radiation therapy (RT) within 5 weeks following breast-conserving surgery (BCS). However, much controversy exists regarding timing of RT. This study investigated its effect on 10-year disease-free survival (DFS) in a Dutch population-based cohort.Methods: All women diagnosed with primary invasive stage I-IIIA breast cancer in 2003 treated with BCS+RT were included. Two populations were studied. Population 1 excluded patients receiving chemotherapy before RT. Analyses were stratified for use of adjuvant systemic therapy (AST). Population 2 included patients treated with chemotherapy, and compared chemotherapy before (BCS-chemotherapy-RT) and after RT (BCS-RT-chemotherapy). DFS was estimated using multivariable Cox regression. Locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were secondary outcomes.Results: Population 1 (n=2759) showed better DFS and DMFS for a time interval of >55 than a time interval of <42 days. Patients treated with AST showed higher DFS for >55 days (hazards ratio (HR) 0.60 (95% confidence interval (CI): 0.38-0.94)) and 42-55 days (HR 0.64 (95% CI: 0.45-0.91)) than <42 days. Results were similar for DMFS, while timing did not affect LRRFS and OS. For patients without AST, timing was not associated with DFS, DMFS and LLRFS, but 10-year OS was significantly lower for 42-55 and >55 days compared to <42 days. In population 2 (n=1120), timing did not affect survival in BCS-chemotherapy-RT. In BCS-RT-chemotherapy, DMFS was higher for >55 than <42 days.Conclusions: Starting RT shortly after BCS seems not to be associated with a better long-term outcome. The common position that RT should start as soon as possible following surgery in order to increase treatment efficacy can be questioned. [ABSTRACT FROM AUTHOR]

Motivation: The molecular dynamics simulation package GROMACS is a widely used tool used in a broad range of different applications within physics, chemistry and biology. It is freely available, user friendly and extremely efficient. The GROMACS software is force field agnostic, and compatible with many molecular dynamics force fields; coarse-grained, unified atom, all atom as well as polarizable models based on the charge on a spring concept. To validate simulations, it is necessary to compare results from the simulations to experimental data. To ease the process of setting up topologies and structures for simulations, as well as providing pre-calculated physical properties along with experimental values for the same we provide a web-based database, containing 145 organic molecules at present.Results: Liquid properties of 145 organic molecules have been simulated using two different force fields, OPLS all atom and Generalized Amber Force Field. So far, eight properties have been calculated (the density, enthalpy of vaporization, surface tension, heat capacity at constant volume and pressure, isothermal compressibility, volumetric expansion coefficient and the static dielectric constant). The results, together with experimental values are available through the database, along with liquid structures and topologies for the 145 molecules, in the two force fields.Availability: The database is freely available under http://virtualchemistry.org.Contact: spoel@xray.bmc.uu.se; carl.caleman@cfel.de [ABSTRACT FROM AUTHOR]

The article presents a case study of a 74-year old female bursitis patient who experienced anaphylactic shock after receiving Kenacort-A® triamcinolone acetonide injection and Xylocaine® lidocaine injection. It states that the patient experienced anaphylactic reactions which involved uticaria, angio-edema, weakness, nausea, and vomiting. It mentions that after intradermal tests, the patient showed positive reactions to the 1:10 000 and 1:1000 dilutions of Kenacort-A®.