The Complexity of Routing with Few Collisions

We study the computational complexity of routing multiple objects through a network in such a way that only few collisions occur: Given a graph $G$ with two distinct terminal vertices and two positive integers $p$ and $k$, the question is whether one can connect the terminals by at least $p$ routes (e.g. paths) such that at most $k$ edges are time-wise shared among them. We study three types of routes: traverse each vertex at most once (paths), each edge at most once (trails), or no such restrictions (walks). We prove that for paths and trails the problem is NP-complete on undirected and directed graphs even if $k$ is constant or the maximum vertex degree in the input graph is constant. For walks, however, it is solvable in polynomial time on undirected graphs for arbitrary $k$ and on directed graphs if $k$ is constant. We additionally study for all route types a variant of the problem where the maximum length of a route is restricted by some given upper bound. We prove that this length-restricted variant has the same complexity classification with respect to paths and trails, but for walks it becomes NP-complete on undirected graphs

Literature review of visual representation of the results of benefit–risk assessments of medicinal products

Background The PROTECT Benefit–Risk group is dedicated to research in methods for continuous benefit–risk monitoring of medicines, including the presentation of the results, with a particular emphasis on graphical methods. Methods A comprehensive review was performed to identify visuals used for medical risk and benefit–risk communication. The identified visual displays were grouped into visual types, and each visual type was appraised based on five criteria: intended audience, intended message, knowledge required to understand the visual, unintentional messages that may be derived from the visual and missing information that may be needed to understand the visual. Results Sixty-six examples of visual formats were identified from the literature and classified into 14 visual types. We found that there is not one single visual format that is consistently superior to others for the communication of benefit–risk information. In addition, we found that most of the drawbacks found in the visual formats could be considered general to visual communication, although some appear more relevant to specific formats and should be considered when creating visuals for different audiences depending on the exact message to be communicated. Conclusion We have arrived at recommendations for the use of visual displays for benefit–risk communication. The recommendation refers to the creation of visuals. We outline four criteria to determine audience–visual compatibility and consider these to be a key task in creating any visual. Next we propose specific visual formats of interest, to be explored further for their ability to address nine different types of benefit–risk analysis information

Recommendations for benefit–risk assessment methodologies and visual representations

Purpose The purpose of this study is to draw on the practical experience from the PROTECT BR case studies and make recommendations regarding the application of a number of methodologies and visual representations for benefit–risk assessment. Methods Eight case studies based on the benefit–risk balance of real medicines were used to test various methodologies that had been identified from the literature as having potential applications in benefit–risk assessment. Recommendations were drawn up based on the results of the case studies. Results A general pathway through the case studies was evident, with various classes of methodologies having roles to play at different stages. Descriptive and quantitative frameworks were widely used throughout to structure problems, with other methods such as metrics, estimation techniques and elicitation techniques providing ways to incorporate technical or numerical data from various sources. Similarly, tree diagrams and effects tables were universally adopted, with other visualisations available to suit specific methodologies or tasks as required. Every assessment was found to follow five broad stages: (i) Planning, (ii) Evidence gathering and data preparation, (iii) Analysis, (iv) Exploration and (v) Conclusion and dissemination. Conclusions Adopting formal, structured approaches to benefit–risk assessment was feasible in real-world problems and facilitated clear, transparent decision-making. Prior to this work, no extensive practical application and appraisal of methodologies had been conducted using real-world case examples, leaving users with limited knowledge of their usefulness in the real world. The practical guidance provided here takes us one step closer to a harmonised approach to benefit–risk assessment from multiple perspectives

Effects of Intracellular Calcium and Actin Cytoskeleton on TCR Mobility Measured by Fluorescence Recovery

Background: The activation of T lymphocytes by specific antigen is accompanied by the formation of a specialized signaling region termed the immunological synapse, characterized by the clustering and segregation of surface molecules and, in particular, by T cell receptor (TCR) clustering. Methodology/Principal Findings: To better understand TCR motion during cellular activation, we used confocal microscopy and photo-bleaching recovery techniques to investigate the lateral mobility of TCR on the surface of human T lymphocytes under various pharmacological treatments. Using drugs that cause an increase in intracellular calcium, we observed a decrease in TCR mobility that was dependent on a functional actin cytoskeleton. In parallel experiments measurement of filamentous actin by FACS analysis showed that raising intracellular calcium also causes increased polymerization of the actin cytoskeleton. These in vitro results were analyzed using a mathematical model that revealed effective binding parameters between TCR and the actin cytoskeleton. Conclusion/Significance: We propose, based on our results, that increase in intracellular calcium levels leads to actin polymerization and increases TCR/cytoskeleton interactions that reduce the overall mobility of the TCR. In a physiological setting, this may contribute to TCR re-positioning at the immunological synapse

Prognostic Factors in 77 Curative Chest Wall Resections for Isolated Breast Cancer Recurrence

Background: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent. Methods: BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed. Results: Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2(P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses. Conclusions: CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients

Colour assessment outcomes – a new approach to grading the severity of color vision loss

INTRODUCTION: Recent studies have shown that a significant percentage of subjects with anomalous, congenital trichromacy can perform the suprathreshold, colour-related tasks encountered in many occupations with the same accuracy as normal trichromats. In the absence of detailed, occupation-specific studies, an alternative approach is to make use of new findings and the statistical outcomes of past practices that have been considered safe to produce graded, justifiable categories of colour vision that can be enforced. METHODS: We analyzed traditional color assessment outcomes and measured severity of colour vision loss using the CAD test in 1363 subjects (336 normals, 705 deutan, 319 protan and 3 tritan). The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. RESULTS: The correlation between the number of Ishihara (IH) test plates subjects fail and the severity of RG colour vision loss was very poor. The 38 plates IH test has high sensitivity when no errors are allowed (i.e., only 0.71% deutans and 0.63% protans pass). Protocols based on zero errors are uncommon since 18.15% of normal trichromats fail. The most common protocols employ either the 24 or the 14 plates editions with two or less errors. These protocols pass almost all normal trichromats, but the deutans and some protans that also pass (when two or less errors are allowed) can be severely deficient. This is simply because the most challenging plates have not been included in the 24 and 14 plates editions. As a result, normals no longer fail, but the deutans and protans that pass have more severe loss of colour vision since they fail less challenging plates. The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. DISCUSSION: Historical evidence and new findings that relate severity of loss to the effective use of colour signals in a number of tasks provide the basis for a new colour grading system based on six categories. A single colour assessment test is needed to establish the applicant’s Colour Vision category which can range from ‘supernormal’ (CV0), for the most stringent, colour-demanding tasks, to ‘severe colour deficiency’, when red / green colour vision is either absent or extremely weak (CV5)

Evaluation of physical activity programmes for the elderly - exploring the lessons from other sectors and examining the general characteristics of the programmes

<p>Abstract</p> <p>Background</p> <p>In Portugal, there are several physical activity (PA) programmes for elderly people developed by the local government. The importance of these programmes has been increasing since the evidence has shown that this type of health promotion interventions may reduce the deleterious effects of the ageing process. However, no study has already identified the general characteristics of these programmes nor if they use any scheme to assess the quality of the service provided. A widely-used scheme is the EFQM Excellence Model, which will be in the core of our present work. Thus, the main aims of this preliminary study were 1) to identify the general characteristics of the PA programmes developed by the Portuguese Local Public Administration 2) to determine the extent of implementation of quality initiatives in these programmes.</p> <p>Methods</p> <p>Data were collected by an on-line questionnaire sent to all Continental Municipalities (n = 278). Categorical data were expressed as absolute counts and percentages. Continuous data were expressed as the mean and SD. An open-ended question was analysed using qualitative content analysis with QSR NVivo software. Associations between categorical variables were tested by the use of contingency tables and the calculation of chi-square tests. Significance level was set at p ≤ 0.05.</p> <p>Results</p> <p>Results showed: i) a total of 125 PA programmes were identified in the 18 districts of the Portugal mainland; ii) the main goal of the majority (95.2%) was the participants' health promotion; iii) different characteristics of the programmes were found according to different regions of the country; iv) certain characteristics of the programmes were associated to the existence of other features; v) only one PA programme developed quality initiatives.</p> <p>Conclusions</p> <p>In conclusion, although there are many PA programmes for elderly people spread throughout the country, aiming at improving the health of participants, the overwhelming majority does not adopt quality control initiatives. Considering that the quality of a service increases customer satisfaction, the continuous quality improvement of the PA programmes for elderly people should therefore be implemented since they can be useful and critical for elderly satisfaction and adherence.</p

Parents' psychological adjustment in families of children with Spina Bifida: a meta-analysis

BACKGROUND: Spina Bifida (SB) is the second most common birth defect worldwide. Since the chances of survival in children with severe SB-forms have increased, medical care has shifted its emphasis from life-saving interventions to fostering the quality of life for these children and their families. Little is known, however, about the impact of SB on family adjustment. Reviewers have struggled to synthesize the few contradictory studies available. In this systematic review a new attempt was made to summarize the findings by using meta-analysis and by delimiting the scope of review to one concept of family adjustment: Parents' psychological adjustment. The questions addressed were: (a) do parents of children with SB have more psychological distress than controls? (b) do mothers and fathers differ? and (c) which factors correlate with variations in psychological adjustment? METHODS: PsycInfo, Medline, and reference lists were scanned. Thirty-three relevant studies were identified of which 15 were eligible for meta-analysis. RESULTS: SB had a negative medium-large effect on parents' psychological adjustment. The effect was more heterogeneous for mothers than for fathers. In the reviewed studies child factors (age, conduct problems, emotional problems, and mental retardation), parent factors (SES, hope, appraised stress, coping, and parenting competence), family factors (family income, partner relationship, and family climate), and environmental factors (social support) were found to be associated with variations in parents' psychological adjustment. CONCLUSION: Meta-analysis proved to be helpful in organizing studies. Clinical implications indicate a need to be especially alert to psychological suffering in mothers of children with SB. Future research should increase sample sizes through multi-center collaborations

Neighborhood deprivation and biomarkers of health in Britain: The mediating role of the physical environment

Background: Neighborhood deprivation has been consistently linked to poor individual health outcomes; however, studies exploring the mechanisms involved in this association are scarce. The objective of this study was to investigate whether objective measures of the physical environment mediate the association between neighborhood socioeconomic deprivation and biomarkers of health in Britain. Methods: We linked individual-level biomarker data from Understanding Society: The UK Household Longitudinal Survey (2010-2012) to neighborhood-level data from different governmental sources. Our outcome variables were forced expiratory volume in 1 s (FEV1%; n=16,347), systolic blood pressure (SBP; n=16,846), body mass index (BMI; n=19,417), and levels of C-reactive protein (CRP; n=11,825). Our measure of neighborhood socioeconomic deprivation was the Carstairs index, and the neighborhood-level mediators were levels of air pollutants (sulphur dioxide [SO2], particulate matter [PM10], nitrogen dioxide [NO2], and carbon monoxide [CO]), green space, and proximity to waste and industrial facilities. We fitted a multilevel mediation model following a multilevel structural equation framework in MPlus v7.4, adjusting for age, gender, and income. Results: Residents of poor neighborhoods and those exposed to higher pollution and less green space had worse health outcomes. However, only SO2exposure significantly and partially mediated the association between neighborhood socioeconomic deprivation and SBP, BMI, and CRP. Conclusion: Reducing air pollution exposure and increasing access to green space may improve population health but may not decrease health inequalities in Britain