ANOVA kernels and RKHS of zero mean functions for model-based sensitivity analysis

Given a reproducing kernel Hilbert space (H,〈.,.〉)(H,〈.,.〉) of real-valued functions and a suitable measure μμ over the source space D⊂RD⊂R, we decompose HH as the sum of a subspace of centered functions for μμ and its orthogonal in HH. This decomposition leads to a special case of ANOVA kernels, for which the functional ANOVA representation of the best predictor can be elegantly derived, either in an interpolation or regularization framework. The proposed kernels appear to be particularly convenient for analyzing the effect of each (group of) variable(s) and computing sensitivity indices without recursivity.

Positive affect moderates the effect of negative affect on cardiovascular disease-related hospitalizations and all-cause mortality after cardiac rehabilitation

BACKGROUND Little is known as to whether negative emotions adversely impact the prognosis of patients who undergo cardiac rehabilitation. We prospectively investigated the predictive value of state negative affect (NA) assessed at discharge from cardiac rehabilitation for prognosis and the moderating role of positive affect (PA) on the effect of NA on outcomes. METHODS A total of 564 cardiac patients (62.49 ± 11.51) completed a comprehensive three-month outpatient cardiac rehabilitation program, filling in the Global Mood Scale (GMS) at discharge. The combined endpoint was cardiovascular disease (CVD)-related hospitalizations plus all-cause mortality at follow-up. Cox regression models estimated the predictive value of NA, as well as the moderating influence of PA on outcomes. Survival models were adjusted for sociodemographic factors, traditional cardiovascular risk factors, and severity of disease. RESULTS During a mean follow-up period of 3.4 years, 71 patients were hospitalized for a CVD-related event and 15 patients died. NA score (range 0-20) was a significant and independent predictor (hazard ratio (HR) 1.091, 95% confidence interval (CI) 1.012-1.175; p = 0.023) with a three-point higher level in NA increasing the relative risk by 9.1%. Furthermore, PA interacted significantly with NA (p < 0.001). The relative risk of poor prognosis with NA was increased in patients with low PA (p = 0.012) but remained unchanged in combination with high PA (p = 0.12). CONCLUSION The combination of NA with low PA was particularly predictive of poor prognosis. Whether reduction of NA and increase of PA, particularly in those with high NA, improves outcome needs to be tested.

Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host.

Salmonella enterica subspecies 1 serovar Typhimurium is a principal cause of human enterocolitis. For unknown reasons, in mice serovar Typhimurium does not provoke intestinal inflammation but rather targets the gut-associated lymphatic tissues and causes a systemic typhoid-like infection. The lack of a suitable murine model has limited the analysis of the pathogenetic mechanisms of intestinal salmonellosis. We describe here how streptomycin-pretreated mice provide a mouse model for serovar Typhimurium colitis. Serovar Typhimurium colitis in streptomycin-pretreated mice resembles many aspects of the human infection, including epithelial ulceration, edema, induction of intercellular adhesion molecule 1, and massive infiltration of PMN/CD18(+) cells. This pathology is strongly dependent on protein translocation via the serovar Typhimurium SPI1 type III secretion system. Using a lymphotoxin beta-receptor knockout mouse strain that lacks all lymph nodes and organized gut-associated lymphatic tissues, we demonstrate that Peyer's patches and mesenteric lymph nodes are dispensable for the initiation of murine serovar Typhimurium colitis. Our results demonstrate that streptomycin-pretreated mice offer a unique infection model that allows for the first time to use mutants of both the pathogen and the host to study the molecular mechanisms of enteric salmonellosis.

Team training to establish a safety culture in dialysis access surgery.

Operating room (OR) team safety training and learning in the field of dialysis access is well suited for the use of simulators, simulated case learning and root cause analysis of adverse outcomes. The objectives of OR team training are to improve communication and leadership skills, to use checklists and to prevent errors. Other objectives are to promote a change in the attitudes towards vascular access from learning through mistakes in a nonpunitive environment, to positively impact the employee performance and to increase staff retention by making the workplace safer, more efficient and user friendly.

High-quality lung fixation by controlled closed loop perfusion for stereological analysis in a large animal model

Stereology is an essential method for quantitative analysis of lung structure. Adequate fixation is a prerequisite for stereological analysis to avoid bias in pulmonary tissue, dimensions and structural details. We present a technique for in situ fixation of large animal lungs for stereological analysis, based on closed loop perfusion fixation.

German Validation of the Conners Adult ADHD Rating Scale-Self-Report: Confirmation of Factor Structure in a Large Sample of Participants With ADHD

Objective: The Conners Adult ADHD Rating Scales (CAARS) assess symptoms specific to adults that are frequently used and have been translated into German. The current study tests the factor structure of the CAARS in a large sample of German adults with ADHD and compares the means of the CAARS subscales with those of healthy German controls. Method: CAARS were completed by 466 participants with ADHD and 851 healthy control participants. Confirmatory factor analysis was used to establish model fit with the American original. Comparisons between participants with ADHD and healthy controls and influences of gender, age, and degree of education were analyzed. Results: Confirmatory factor analysis showed a very good fit with the model for the American original. Differences between ADHD participants and healthy controls on all Conners Adult ADHD Rating Scales-Self-Report (CAARS-S) subscales were substantial and significant. Conclusion: The factor structure of the original American model was successfully replicated in this sample of adult German ADHD participants. (J. of Att. Dis. 2012; XX(X) 1-XX).

Flavor-phenomenology of two-Higgs-doublet models with generic Yukawa structure

In this article, we perform an extensive study of flavor observables in a two-Higgs-doublet model with generic Yukawa structure (of type III). This model is interesting not only because it is the decoupling limit of the minimal supersymmetric standard model but also because of its rich flavor phenomenology which also allows for sizable effects not only in flavor-changing neutral-current (FCNC) processes but also in tauonic B decays. We examine the possible effects in flavor physics and constrain the model both from tree-level processes and from loop observables. The free parameters of the model are the heavy Higgs mass, tanβ (the ratio of vacuum expectation values) and the “nonholomorphic” Yukawa couplings ϵfij(f=u,d,ℓ). In our analysis we constrain the elements ϵfij in various ways: In a first step we give order of magnitude constraints on ϵfij from ’t Hooft’s naturalness criterion, finding that all ϵfij must be rather small unless the third generation is involved. In a second step, we constrain the Yukawa structure of the type-III two-Higgs-doublet model from tree-level FCNC processes (Bs,d→μ+μ−, KL→μ+μ−, D¯¯¯0→μ+μ−, ΔF=2 processes, τ−→μ−μ+μ−, τ−→e−μ+μ− and μ−→e−e+e−) and observe that all flavor off-diagonal elements of these couplings, except ϵu32,31 and ϵu23,13, must be very small in order to satisfy the current experimental bounds. In a third step, we consider Higgs mediated loop contributions to FCNC processes [b→s(d)γ, Bs,d mixing, K−K¯¯¯ mixing and μ→eγ] finding that also ϵu13 and ϵu23 must be very small, while the bounds on ϵu31 and ϵu32 are especially weak. Furthermore, considering the constraints from electric dipole moments we obtain constrains on some parameters ϵu,ℓij. Taking into account the constraints from FCNC processes we study the size of possible effects in the tauonic B decays (B→τν, B→Dτν and B→D∗τν) as well as in D(s)→τν, D(s)→μν, K(π)→eν, K(π)→μν and τ→K(π)ν which are all sensitive to tree-level charged Higgs exchange. Interestingly, the unconstrained ϵu32,31 are just the elements which directly enter the branching ratios for B→τν, B→Dτν and B→D∗τν. We show that they can explain the deviations from the SM predictions in these processes without fine-tuning. Furthermore, B→τν, B→Dτν and B→D∗τν can even be explained simultaneously. Finally, we give upper limits on the branching ratios of the lepton flavor-violating neutral B meson decays (Bs,d→μe, Bs,d→τe and Bs,d→τμ) and correlate the radiative lepton decays (τ→μγ, τ→eγ and μ→eγ) to the corresponding neutral current lepton decays (τ−→μ−μ+μ−, τ−→e−μ+μ− and μ−→e−e+e−). A detailed Appendix contains all relevant information for the considered processes for general scalar-fermion-fermion couplings.

Coupled human and natural system dynamics as key to the sustainability of Lake Victoria's ecosystem services

East Africa’s Lake Victoria provides resources and services to millions of people on the lake’s shores and abroad. In particular, the lake’s fisheries are an important source of protein, employment, and international economic connections for the whole region. Nonetheless, stock dynamics are poorly understood and currently unpredictable. Furthermore, fishery dynamics are intricately connected to other supporting services of the lake as well as to lakeshore societies and economies. Much research has been carried out piecemeal on different aspects of Lake Victoria’s system; e.g., societies, biodiversity, fisheries, and eutrophication. However, to disentangle drivers and dynamics of change in this complex system, we need to put these pieces together and analyze the system as a whole. We did so by first building a qualitative model of the lake’s social-ecological system. We then investigated the model system through a qualitative loop analysis, and finally examined effects of changes on the system state and structure. The model and its contextual analysis allowed us to investigate system-wide chain reactions resulting from disturbances. Importantly, we built a tool that can be used to analyze the cascading effects of management options and establish the requirements for their success. We found that high connectedness of the system at the exploitation level, through fisheries having multiple target stocks, can increase the stocks’ vulnerability to exploitation but reduce society’s vulnerability to variability in individual stocks. We describe how there are multiple pathways to any change in the system, which makes it difficult to identify the root cause of changes but also broadens the management toolkit. Also, we illustrate how nutrient enrichment is not a self-regulating process, and that explicit management is necessary to halt or reverse eutrophication. This model is simple and usable to assess system-wide effects of management policies, and can serve as a paving stone for future quantitative analyses of system dynamics at local scales.

Chlorhexidine and preservation of sound tooth structure in older adults. A placebo-controlled trial

The Trial to Enhance Elderly Teeth Health (TEETH) was designed to test the impact of regular rinsing with a 0.12% chlorhexidine (CHX) solution on tooth loss, and the causes of tooth loss (caries, periodontal disease and trauma) were also investigated. This paper reports on the effectiveness of a 0.12% CHX solution for controlling caries using a tooth surface (coronal and root) survival analysis. A total of 1,101 low income elders in Seattle (United States) and Vancouver (Canada), aged 60-75 years, were recruited for a double-blind clinical trial and assigned to either a CHX (n = 550) or a placebo (n = 551) mouth rinse. Subjects alternated between daily rinsing for 1 month, followed by weekly rinsing for 5 months. All sound coronal and root surfaces at baseline were followed annually for up to 5 years. At each follow-up examination, those tooth surfaces with caries, restored, or extracted were scored as 'carious'. The hazard ratio associated with CHX for a sound surface to become filled, decayed, or extracted was 0.87 for coronal surfaces (95% confidence interval: 0.71-1.14, p = 0.20) and 0.91 for root surfaces (95% confidence interval: 0.73-1.14, p = 0.41). These findings suggest that regular rinsing with CHX does not have a substantial effect on the preservation of sound tooth structure in older adults.

Affective attitudes to face images associated with intracerebral EEG source location before face viewing

We investigated whether different, personality-related affective attitudes are associated with different brain electric field (EEG) sources before any emotional challenge (stimulus exposure). A 27-channel EEG was recorded in 15 subjects during eyes-closed resting. After recording, subjects rated 32 images of human faces for affective appeal. The subjects in the first (i.e., most negative) and fourth (i.e., most positive) quartile of general affective attitude were further analyzed. The EEG data (mean=25±4.8 s/subject) were subjected to frequency-domain model dipole source analysis (FFT-Dipole-Approximation), resulting in 3-dimensional intracerebral source locations and strengths for the delta–theta, alpha, and beta EEG frequency band, and for the full range (1.5–30 Hz) band. Subjects with negative attitude (compared to those with positive attitude) showed the following source locations: more inferior for all frequency bands, more anterior for the delta–theta band, more posterior and more right for the alpha, beta and 1.5–30 Hz bands. One year later, the subjects were asked to rate the face images again. The rating scores for the same face images were highly correlated for all subjects, and original and retest affective mean attitude was highly correlated across subjects. The present results show that subjects with different affective attitudes to face images had different active, cerebral, neural populations in a task-free condition prior to viewing the images. We conclude that the brain functional state which implements affective attitude towards face images as a personality feature exists without elicitors, as a continuously present, dynamic feature of brain functioning.

Observational Research on NCDs in HIV-Positive Populations: Conceptual and Methodological Considerations

: Noncommunicable diseases (NCDs) account for a growing burden of morbidity and mortality among people living with HIV in low- and middle-income countries (LMICs). HIV infection and antiretroviral therapy interact with NCD risk factors in complex ways, and research into this "web of causation" has so far been largely based on data from high-income countries. However, improving the understanding, treatment, and prevention of NCDs in LMICs requires region-specific evidence. Priority research areas include: (1) defining the burden of NCDs among people living with HIV, (2) understanding the impact of modifiable risk factors, (3) evaluating effective and efficient care strategies at individual and health systems levels, and (4) evaluating cost-effective prevention strategies. Meeting these needs will require observational data, both to inform the design of randomized trials and to replace trials that would be unethical or infeasible. Focusing on Sub-Saharan Africa, we discuss data resources currently available to inform this effort and consider key limitations and methodological challenges. Existing data resources often lack population-based samples; HIV-negative, HIV-positive, and antiretroviral therapy-naive comparison groups; and measurements of key NCD risk factors and outcomes. Other challenges include loss to follow-up, competing risk of death, incomplete outcome ascertainment and measurement of factors affecting clinical decision making, and the need to control for (time-dependent) confounding. We review these challenges and discuss strategies for overcoming them through augmented data collection and appropriate analysis. We conclude with recommendations to improve the quality of data and analyses available to inform the response to HIV and NCD comorbidity in LMICs.

Granular layer in the periplasmic space of gram-positive bacteria and fine structures of Enterococcus gallinarum and Streptococcus gordonii septa revealed by cryo-electron microscopy of vitreous sections.

High-resolution structural information on optimally preserved bacterial cells can be obtained with cryo-electron microscopy of vitreous sections. With the help of this technique, the existence of a periplasmic space between the plasma membrane and the thick peptidoglycan layer of the gram-positive bacteria Bacillus subtilis and Staphylococcus aureus was recently shown. This raises questions about the mode of polymerization of peptidoglycan. In the present study, we report the structure of the cell envelope of three gram-positive bacteria (B. subtilis, Streptococcus gordonii, and Enterococcus gallinarum). In the three cases, a previously undescribed granular layer adjacent to the plasma membrane is found in the periplasmic space. In order to better understand how nascent peptidoglycan is incorporated into the mature peptidoglycan, we investigated cellular regions known to represent the sites of cell wall production. Each of these sites possesses a specific structure. We propose a hypothetic model of peptidoglycan polymerization that accommodates these differences: peptidoglycan precursors could be exported from the cytoplasm to the periplasmic space, where they could diffuse until they would interact with the interface between the granular layer and the thick peptidoglycan layer. They could then polymerize with mature peptidoglycan. We report cytoplasmic structures at the E. gallinarum septum that could be interpreted as cytoskeletal elements driving cell division (FtsZ ring). Although immunoelectron microscopy and fluorescence microscopy studies have demonstrated the septal and cytoplasmic localization of FtsZ, direct visualization of in situ FtsZ filaments has not been obtained in any electron microscopy study of fixed and dehydrated bacteria.