A Multistage Stochastic Programming Approach to the Dynamic and Stochastic VRPTW - Extended version

We consider a dynamic vehicle routing problem with time windows and stochastic customers (DS-VRPTW), such that customers may request for services as vehicles have already started their tours. To solve this problem, the goal is to provide a decision rule for choosing, at each time step, the next action to perform in light of known requests and probabilistic knowledge on requests likelihood. We introduce a new decision rule, called Global Stochastic Assessment (GSA) rule for the DS-VRPTW, and we compare it with existing decision rules, such as MSA. In particular, we show that GSA fully integrates nonanticipativity constraints so that it leads to better decisions in our stochastic context. We describe a new heuristic approach for efficiently approximating our GSA rule. We introduce a new waiting strategy. Experiments on dynamic and stochastic benchmarks, which include instances of different degrees of dynamism, show that not only our approach is competitive with state-of-the-art methods, but also enables to compute meaningful offline solutions to fully dynamic problems where absolutely no a priori customer request is provided.Comment: Extended version of the same-name study submitted for publication in conference CPAIOR201

Time to tweak the TTO: results from a comparison of alternative specifications of the TTO

Abstract This article examines the effect that different specifications of the time trade-off (TTO) valuation task may have on values for EQ-5D-5L health states. The new variants of the TTO, namely lead-time TTO and lag-time TTO, along with the classic approach to TTO were compared using two durations for the health states (15 and 20 years). The study tested whether these methods yield comparable health-state values. TTO tasks were administered online. It was found that lag-time TTO produced lower values than lead-time TTO and that the difference was larger in the longer time frame. Classic TTO values most resembled those of the lag-time TTO in a 20-year time frame in terms of mean absolute difference. The relative importance of different domains of health was systematically affected by the duration of the health state. In the tasks with a 10-year health-state duration, anxiety/ depression had the largest negative impact on health-state values; in the tasks with a 5-year duration, the pain/discomfort domain had the largest negative impact

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Introducing the composite time trade-off: a test of feasibility and face validity

__Abstract__ __Introduction__ This study was designed to test the feasibility and face validity of the composite time trade-off (composite TTO), a new approach to TTO allowing for a more consistent elicitation of negative health state values. __Methods__ The new instrument combines a conventional TTO to elicit values for states regarded better than dead and a lead-time TTO for states worse than dead. __Results__ A total of 121 participants completed the composite TTO for ten EQ-5D-5L health states. Mean values ranged from −0.104 for health state 53555 to 0.946 for 21111. The instructions were clear to 98 % of the respondents, and 95 % found the task easy to understand, indicating feasibility. Further, the average number of steps taken in the iteration procedure to achieve the point of indifference in the TTO and the average duration of each task were indicative of a deliberate cognitive process. __Conclusion__ Face validity was confirmed by the high mean values for the mild health states (>0.90) and low mean values for the severe states (<0.42). In conclusion, this study demonstrates the feasibility and face validity of the composite TTO in a face-to-face standardized computer-assisted interview setting

On the (not so) constant proportional trade-off in TTO

Abstract. Purpose: The linear and power QALY models require that people in Time Trade-off (TTO) exercises sacrifice the same proportion of lifetime to obtain a health improvement, irrespective of the absolute amount. However, evidence on these constant proportional trade-offs (CPTOs) is mixed, indicating that these versions of the QALY model do not represent preferences. Still, it may be the case that a more general version of the QALY model represents preferences. This version has the property that people want to sacrifice the same proportion of utilities of lifetime for a health improvement, irrespective of the amount of this lifetime. Methods: We use a new method to correct TTO scores for utility of life duration and test whether decision makers trade off utility of duration and quality at the same rate irrespective of duration. Results: We find a robust violation of CPTO for both uncorrected and corrected TTO scores. Remarkably, we find higher values for longer durations, contrary to most previous studies. This represents the only study correcting for utility of life duration to find such a violation. Conclusions: It seems that the trade-off of life years is indeed not so constantly proportional and, therefore, that health state valuations depend on durations

Dealing with the health state ‘dead’ when using discrete choice experiments to obtain values for EQ-5D-5L heath states - Springer

__Abstract__ __Objective__ : To evaluate two different methods to obtain a dead (0)—full health (1) scale for EQ-5D-5L valuation studies when using discrete choice (DC) modeling. __Method__ : The study was carried out among 400 respondents from Barcelona who were representative of the Spanish population in terms of age, sex, and level of education. The DC design included 50 pairs of health states in five blocks. Participants were forced to choose between two EQ-5D-5L states (A and B). Two extra questions concerned whether A and B were considered worse than dead. Each participant performed ten choice exercises. In addition, values were collected using lead-time trade-off (lead-time TTO), for which 100 states in ten blocks were selected. Each participant performed five lead-time TTO exercises. These consisted of DC models offering the health state ‘dead’ as one of the choices—for which all participants’ responses were used (DCdead)—and a model that included only the responses of participants who chose at least one state as worse than dead (WTD) (DCWTD). The study also estimated DC models rescaled with lead-time TTO data and a lead-time TTO linear model. __Results__ : The DCdead and DCWTD models produced relatively similar results, although the coefficients in the DCdead model were slightly lower. The DC model rescaled with lead-time TTO data produced higher utility decrements. Lead-time TTO produced the highest utility decrements. __Conclusions__: The incorporation of the state ‘dead’ in the DC models produces results in concordance with DC models that do not include ‘dead’

The catch 22 of condoms in US correctional facilities

<p>Abstract</p> <p>Background</p> <p>Despite the high prevalence of sexually transmitted infections (STIs) and HIV infection in US correctional settings, most jails and prisons in the United States prevent inmates from using condoms to prevent STIs/HIV.</p> <p>Discussion</p> <p>This article makes the following arguments to justify a scalable and feasible next step in the prevention of HIV/STIs among inmates: condoms are a basic and essential part of HIV/STI prevention, HIV/STI transmission occurs in the context of corrections, and several model programs show the feasibility of condom distribution in prisons. A lower end estimate for HIV incidence among incarcerated applied to 2,000,000 new inmates annually results in thousands of new HIV infections acquired each year in corrections that could be prevented with condoms in corrections facilities. Programs from parts of the United States, Canada, and much of Europe show how programs distributing condoms in correctional facilities can be safe and effective.</p> <p>Summary</p> <p>Public health and corrections officials must work together to ensure that condoms and broader sexual disease prevention programs are integrated into US jail and prison health systems.</p

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Protocol for the CUPIDO trials; multicenter randomized controlled trials to assess the value of combining prolapse surgery and incontinence surgery in patients with genital prolapse and evident stress incontinence (CUPIDO I) and in patients with genital prolapse and occult stress incontinence (CUPIDO II)

Background: About 40% of all patients with genital prolapse report stress-incontinence. In about half of the 60% patients that do not report stress-incontinence, occult urinary stress-incontinence can be detected. In these patients stress-incontinence is masked due to kinking or compression of the urethra by the prolapse. In case surgical correction is indicated there are two strategies to manage patients with combined prolapse and (occult) stress incontinence. This strategy is either (i) a combination of prolapse surgery and stress-incontinence surgery or (ii) to correct the prolapse first and evaluate afterwards whether additional stress-incontinence surgery is indicated. The advantage of combining prolapse and stress-incontinence surgery is that only few patients report stress-incontinence following such combination. However, this combination has been associated with an increased risk on complications, of which the development of obstructive micturition symptoms, overactive bladder symptoms and bladder retention are the most important ones. Furthermore, combining two procedures may be unnecessary as performing only prolapse surgery may cure stress-incontinence In the randomized CUPIDO trials both strategies are compared in patients with prolapse and evident stress incontinence (CUPIDO I trial) and in patients with prolapse and occult stress incontinence (CUPIDO II trial). Methods/Design: The CUPIDO trials are two multicenter randomized controlled trials in which women with stress urinary incontinence (SUI) or occult stress urinary incontinence (OSUI) are randomized to prolapse surgery combined with anti incontinence surgery (concomitant surgery) or to prolapse surgery only. Patients with at least stage 2 POP are eligible, women with evident SUI are randomized in CUPIDO I. Patients without SUI are eligible for CUPIDO II and will have urodynamic evaluation or a standardized redression test. Women with OSUI are randomized, women without OSUI are followed up but not randomized. The primary outcome measure is absence of SUI twelve months after surgery. Furthermore, economic evaluations are conducted, and the effectiveness of urodynamic investigation is evaluated against a non-invasive way to determine SUI in women with POP. A total of 450 women will be included in the study