Combining filter method and dynamically dimensioned search for constrained global optimization

In this work we present an algorithm that combines the filter technique and the dynamically dimensioned search (DDS) for solving nonlinear and nonconvex constrained global optimization problems. The DDS is a stochastic global algorithm for solving bound constrained problems that in each iteration generates a randomly trial point perturbing some coordinates of the current best point. The filter technique controls the progress related to optimality and feasibility defining a forbidden region of points refused by the algorithm. This region can be given by the flat or slanting filter rule. The proposed algorithm does not compute or approximate any derivatives of the objective and constraint functions. Preliminary experiments show that the proposed algorithm gives competitive results when compared with other methods.The first author thanks a scholarship supported by the International Cooperation Program CAPES/ COFECUB at the University of Minho. The second and third authors thanks the support given by FCT (Funda¸c˜ao para Ciˆencia e Tecnologia, Portugal) in the scope of the projects: UID/MAT/00013/2013 and UID/CEC/00319/2013. The fourth author was partially supported by CNPq-Brazil grants 308957/2014-8 and 401288/2014-5.info:eu-repo/semantics/publishedVersio

Bedside Interactions from the Other Side of the Bedrail

To assess the importance to patients of various aspects of bedside interactions with physician teams. Design : Cross-sectional survey. Setting : VA hospital. Patients : Ninety-seven medical inpatients. Intervention : Survey of 44 questions including short answer, multiple choice, and Likert-type questions. Measurements and Main Results : Data analysis included descriptive statistics. The sample was predominantly male, with a mean age of 62. Overall satisfaction with the hospital experience and with the team of doctors were both high (95% and 96% reported being very or mostly satisfied, respectively). Patients reported learning about several issues during their interactions with the teams; the 3 most highly rated areas were new problems, tests that will be done, and treatments that will be done. Most patients (76%) felt that their teams cared about them very much. Patients were made comfortable when the team showed that they cared, listened, and appeared relaxed (reported by 63%, 57%, and 54%, respectively). Patients were made uncomfortable by the team using language they did not understand (22%) and when several people examined them at once (13%). Many (58%) patients felt personally involved in teaching. The majority of patients liked having medical students and residents involved in their care (69% and 64%, respectively). Conclusions : Patients have much to teach about what is important about interacting with physician teams. Although patients' reactions to team interactions are generally positive, patients are different with respect to what makes them comfortable and uncomfortable. Taking their preferences into account could improve the experience of being in a teaching hospital.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75456/1/j.1525-1497.2005.40192.x.pd

MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME)

Chronic Fatigue Syndrome (CFS/ME) is a complex multisystem disease of unknown aetiology which causes debilitating symptoms in up to 1% of the global population. Although a large cohort of genes have been shown to exhibit altered expression in CFS/ME patients, it is currently unknown whether microRNA (miRNA) molecules which regulate gene translation contribute to disease pathogenesis. We hypothesized that changes in microRNA expression in patient leukocytes contribute to CFS/ME pathology, and may therefore represent useful diagnostic biomarkers that can be detected in the peripheral blood of CFS/ME patients.miRNA expression in peripheral blood mononuclear cells (PBMC) from CFS/ME patients and healthy controls was analysed using the Ambion Bioarray V1. miRNA demonstrating differential expression were validated by qRT-PCR and then replicated in fractionated blood leukocyte subsets from an independent patient cohort. The CFS/ME associated miRNA identified by these experiments were then transfected into primary NK cells and gene expression analyses conducted to identify their gene targets.Microarray analysis identified differential expression of 34 miRNA, all of which were up-regulated. Four of the 34 miRNA had confirmed expression changes by qRT-PCR. Fractionating PBMC samples by cell type from an independent patient cohort identified changes in miRNA expression in NK-cells, B-cells and monocytes with the most significant abnormalities occurring in NK cells. Transfecting primary NK cells with hsa-miR-99b or hsa-miR-330-3p, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity, suggesting that defective NK cell function contributes to CFS/ME pathology.This study demonstrates altered microRNA expression in the peripheral blood mononuclear cells of CFS/ME patients, which are potential diagnostic biomarkers. The greatest degree of miRNA deregulation was identified in NK cells with targets consistent with cellular activation and altered effector function

Techniques for direct experimental evaluation of structure-transport relationships in disordered porous solids

Determining structure-transport relationships is critical to optimising the activity and selectivity performance of porous pellets acting as heterogeneous catalysts for diffusion-limited reactions. For amorphous porous systems determining the impact of particular aspects of the void space on mass transport often requires complex characterization and modelling steps to deconvolve the specific influence of the feature in question. These characterization and modelling steps often have limited accuracy and precision. It is the purpose of this work to present a case-study demonstrating the use of a more direct experimental evaluation of the impact of pore network features on mass transport. The case study evaluated the efficacy of the macropores of a bidisperse porous foam structure on improving mass transport over a purely mesoporous system. The method presented involved extending the novel integrated gas sorption and mercury porosimetry method to include uptake kinetics. Results for the new method were compared with those obtained by the alternative NMR cryodiffusometry technique, and found to lead to similar conclusions. It was found that the experimentally-determined degree of influence of the foam macropores was in line with expectations from a simple resistance model for a disconnected macropore network

Validation of a self-efficacy instrument and its relationship to performance of crisis resource management skills

Self-efficacy is thought to be important for resuscitation proficiency in that it influences the development of and access to the associated medical knowledge, procedural skills and crisis resource management (CRM) skills. Since performance assessment of CRM skills is challenging, self-efficacy is often used as a measure of competence in this area. While self-efficacy may influence performance, the true relationship between self-efficacy and performance in this setting has not been delineated. We developed an instrument to measure pediatric residents’ self-efficacy in CRM skills and assessed its content validity, internal structure, and relationship to other variables. After administering the instrument to 125 pediatric residents, critical care fellows and faculty, we performed an exploratory factor analysis within a confirmatory factor analysis as well as a known group comparison. The analyses specified four factors that we defined as: situation awareness, team management, environment management, and decision making. Pediatric residents reported lower self-efficacy than fellows and faculty in each factor. We also examined the correlation between self-efficacy and performance scores for a subset of 30 residents who led video recorded simulated resuscitations and had their performances rated by three observers. We found a significant, positive correlation between residents’ self-efficacy in situation awareness and environment management and their overall performance of CRM skills. Our findings suggest that in a specific context, self-efficacy as a form of self-assessment may be informative with regards to performance

PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection.

Chronic HBV (CHB) infection suppresses virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a dual-staining method that utilizes hepatitis B virus (HBV) surface antigens (HBsAg) labeled with fluorochromes as "baits" for specific ex vivo detection of HBsAg-specific B cells and analysis of their quantity, function, and phenotype. We studied healthy vaccinated subjects (n = 18) and patients with resolved (n = 21), acute (n = 11), or chronic (n = 96) HBV infection and observed that frequencies of circulating HBsAg-specific B cells were independent of HBV infection status. In contrast, the presence of serum HBsAg affected function and phenotype of HBsAg-specific B cells that were unable to mature in vitro into Ab-secreting cells and displayed an increased expression of markers linked to hyperactivation (CD21lo) and exhaustion (PD-1). Importantly, B cell alterations were not limited to HBsAg-specific B cells, but affected the global B cell population. HBsAg-specific B cell maturation could be partially restored by a method involving the combination of the cytokines IL-2 and IL-21 and CD40L-expressing feeder cells and was further boosted by the addition of anti-PD-1 Abs. In conclusion, HBV infection has a marked impact on global and HBV-specific humoral immunity, yet HBsAg-specific B cells are amenable to a partial rescue by B cell-maturing cytokines and PD-1 blockade

Image informatics strategies for deciphering neuronal network connectivity

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies

Filter-based stochastic algorithm for global optimization

We propose the general Filter-based Stochastic Algorithm (FbSA) for the global optimization of nonconvex and nonsmooth constrained problems. Under certain conditions on the probability distributions that generate the sample points, almost sure convergence is proved. In order to optimize problems with computationally expensive black-box objective functions, we develop the FbSA-RBF algorithm based on the general FbSA and assisted by Radial Basis Function (RBF) surrogate models to approximate the objective function. At each iteration, the resulting algorithm constructs/updates a surrogate model of the objective function and generates trial points using a dynamic coordinate search strategy similar to the one used in the Dynamically Dimensioned Search method. To identify a promising best trial point, a non-dominance concept based on the values of the surrogate model and the constraint violation at the trial points is used. Theoretical results concerning the sufficient conditions for the almost surely convergence of the algorithm are presented. Preliminary numerical experiments show that the FbSA-RBF is competitive when compared with other known methods in the literature.The authors are grateful to the anonymous referees for their fruitful comments and suggestions.The first and second authors were partially supported by Brazilian Funds through CAPES andCNPq by Grants PDSE 99999.009400/2014-01 and 309303/2017-6. The research of the thirdand fourth authors were partially financed by Portuguese Funds through FCT (Fundação para Ciência e Tecnologia) within the Projects UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM and UIDB/00319/2020

The effectiveness of interventions to change six health behaviours: a review of reviews

Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency). Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis. Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities. Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p

Holocene dynamics of the Southern Hemisphere westerly winds and possible links to CO2 outgassing

The Southern Hemisphere westerly winds (SHW) play an important role in regulating the capacity of the Southern Ocean carbon sink. They modulate upwelling of carbon-rich deep water and, with sea ice, determine the ocean surface area available for air–sea gas exchange. Some models indicate that the current strengthening and poleward shift of these winds will weaken the carbon sink. If correct, centennial- to millennial-scale reconstructions of the SHW intensity should be linked with past changes in atmospheric CO2, temperature and sea ice. Here we present a 12,300-year reconstruction of wind strength based on three independent proxies that track inputs of sea-salt aerosols and minerogenic particles accumulating in lake sediments on sub-Antarctic Macquarie Island. Between about 12.1 thousand years ago (ka) and 11.2 ka, and since about 7 ka, the wind intensities were above their long-term mean and corresponded with increasing atmospheric CO2. Conversely, from about 11.2 to 7.2 ka, the wind intensities were below their long-term mean and corresponded with decreasing atmospheric CO2. These observations are consistent with model inferences of enhanced SHW contributing to the long-term outgassing of CO2 from the Southern Ocean