Optimisation of stochastic networks with blocking: a functional-form approach

This paper introduces a class of stochastic networks with blocking, motivated by applications arising in cellular network planning, mobile cloud computing, and spare parts supply chains. Blocking results in lost revenue due to customers or jobs being permanently removed from the system. We are interested in striking a balance between mitigating blocking by increasing service capacity, and maintaining low costs for service capacity. This problem is further complicated by the stochastic nature of the system. Owing to the complexity of the system there are no analytical results available that formulate and solve the relevant optimization problem in closed form. Traditional simulation-based methods may work well for small instances, but the associated computational costs are prohibitive for networks of realistic size. We propose a hybrid functional-form based approach for finding the optimal resource allocation, combining the speed of an analytical approach with the accuracy of simulation-based optimisation. The key insight is to replace the computationally expensive gradient estimation in simulation optimisation with a closed-form analytical approximation that is calibrated using a single simulation run. We develop two implementations of this approach and conduct extensive computational experiments on complex examples to show that it is capable of substantially improving system performance. We also provide evidence that our approach has substantially lower computational costs compared to stochastic approximation

Factors of resilience in informal caregivers of people with dementia from integrative international data analysis

Background/Aims: Although caring for a person with dementia can be stressful, some caregivers appear to experience few negative consequences to their well-being. This study aimed to examine what proportion of caregivers demonstrates resilience under different challenging circumstances and to identify factors related to their resilience. Methods: Baseline data from 4 studies from the Netherlands and UK among informal caregivers of people with dementia were harmonized and integrated. Caregiver resilience was defined as high levels of psychological well-being despite different types of high caregiving demands. Multivariate regression analyses identified factors significantly related to caregiver resilience. Results: The integrated data set included 15 harmonized variables with data from 1,048 caregivers facing a high care demand. The prevalence of resilience varied between 35 and 43%, depending on the demand for high care. Being a male caregiver, caring for a female, living apart from your relative, and low caregiver burden were positively related to caregiver resilience. Conclusion: Caregivers have the capacity to demonstrate resilience despite significant challenges. This study demonstrates how harmonization of data from multiple existing studies can be used to increase power and explore the consistency of findings. This contributes to a better understanding of which factors are likely to facilitate caregiver resilience and offers insights for developing services

Comparing the sensitivities of two screening tests in nonblinded randomized paired screen-positive trials with differential screening uptake

Before a new screening test can be used in routine screening, its performance needs to be compared to the standard screening test. This comparison is generally done in population screening trials with a screen-positive design where participants undergo one or both screening tests after which disease verification takes place for those positive on at least one screening test. We consider the randomized paired screen-positive design of Alonzo and Kittelson where participants are randomized to receive one of the two screening tests and only participants with a positive screening test subsequently receive the other screening test followed by disease verification. The tests are usually offered in an unblinded fashion in which case the screening uptake may differ between arms, in particular when one test is more burdensome than the other. When uptake is associated with disease, the estimator for the relative sensitivity derived by Alonzo and Kittelson may be biased and the type I error of the associated statistical test is no longer guaranteed to be controlled. We present methods for comparing sensitivities of screening tests in randomized paired screen-positive trials that are robust to differential screening uptake. In a simulation study, we show that our methods adequately control the type I error when screening uptake is associated with disease. We apply the developed methods to data from the IMPROVE trial, a nonblinded cervical cancer screening trial comparing the accuracy of HPV testing on self-collected versus provider-collected samples. In this trial, screening uptake was higher among participants randomized to self-collection

Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment

AimsCD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and resultsWe conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a live polling' pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair ( = 0.12-0.35 for CD30-positive tumour cell percentage and = 0.16-0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity ( = 0.30-0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal ( = 0.35-0.60). ConclusionsLack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response

Case finding of mild cognitive impairment and dementia and subsequent care; results of a cluster RCT in primary care

Purpose Despite a call for earlier diagnosis of dementia, the diagnostic yield of case finding and its impact on the mental health of patients and relatives are unclear. This study assessed the effect of a two-component intervention of case finding and subsequent care on these outcomes. Methods In a cluster RCT we assessed whether education of family physicians (FPs; trial stage 1) resulted in more mild cognitive impairment (MCI) and dementia diagnoses among older persons in whom FPs suspected cognitive decline and whether case finding by a practice nurse and the FP (trial stage 2) added to this number of diagnoses. In addition, we assessed mental health effects of case finding and subsequent care (trial stage 2). FPs of 15 primary care practices (PCPs = clusters) judged the cognitive status of all persons ≤ 65 years. The primary outcome, new MCI and dementia diagnoses by FPs after 12 months as indicated on a list, was assessed among all persons in whom FPs suspected cognitive impairment but without a formal diagnosis of dementia. The secondary outcome, mental health of patients and their relatives, was assessed among persons consenting to participate in trial stage 2. Trial stage 1 consisted of either intervention component 1: training FPs to diagnose MCI and dementia, or control: no training. Trial stage 2 consisted of either intervention component 2: case finding of MCI and dementia and care by a trained nurse and the FP, or control: care as usual. Results Seven PCPs were randomized to the intervention; eight to the control condition. MCI or dementia was diagnosed in 42.3 (138/326) of persons in the intervention, and in 30.5 (98/321) in the control group (estimated difference GEE: 10.8, OR: 1.51, 95-CI 0.60-3.76). Among patients and relatives who consented to stage 2 of the trial (n = 145; 25), there were no differences in mental health between the intervention and control group. Conclusions We found a non-significant increase in the number of new MCI diagnoses. As we cannot exclude a clinically relevant effect, a larger study is warranted to replicate ours. Trial Registration Nederlands Trial Register NTR3389 © 2016 van den Dungen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Temperament Traits and Psychopathology in Young Clinically Referred Children Compared to a General Population Sample

Evidence from general population studies shows the contribution of various temperament traits to the development of child psychopathology. Little is known about which traits are associated with internalizing and externalizing problems in young clinically referred children. The current study assessed temperament and internalizing and externalizing problems in 216 referred children (M = 4.35 years, SD 0.89, 81% boys). A comparison was made with an age and gender matched general population sample. Referred children showed less effortful control than general population children. Less effortful control and more negative affectivity were associated with more internalizing and externalizing problems across groups. Surgency, and specifically temperamental impulsivity, was more strongly associated with externalizing problems in referred children compared to general population. Less soothability, less inhibitory control and more frustration predicted (sub)clinical levels of comborbid internalizing and externalizing problems in referred children. The results can be used in diagnostic and treatment procedures in early childhood

Work Motivation and Employment Outcomes in People with Severe Mental Illness

Purpose To study associations between the level of self-reported work motivation and employment outcomes in people with severe mental illness (SMI) enrolled in a vocational rehabilitation program. Methods Data of 151 study participants, collected from a randomised controlled trial with a 30-month follow-up period, were used for a secondary data analysis. Multiple logistic regression, linear regression and cox regression analyses were performed to analyse the association between the level of work motivation at baseline and job obtainment, duration of job, and time until job obtainment during the 30-month follow-up period. Results No statistically significant associations were found between the level of work motivation and job obtainment (OR 1.83, 95% CI 0.55-6.06, p = 0.32), job duration (B = - 0.74, 95% CI - 2.37 to 0.89, p = 0.37, R-squared = 0.03), or time until job obtainment (HR = 1.53, 95% CI 0.64-3.68, p = 0.34). Conclusions The results of this study show no statistically significant associations between the level of work motivation and employment outcomes in people with SMI enrolled in a vocational rehabilitation program. These associations may be underestimated due to range restriction of the work motivation's level. Further research is recommended to increase knowledge on the associations between work motivation and employment outcomes, as it could be relevant for further understanding success in vocational rehabilitation