Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function.

INTRODUCTION: The objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis. METHODS: Twenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP). RESULTS: MAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003). CONCLUSIONS: The MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.

Pulmonary veins to left atrium cycle length gradient predicts procedural and clinical outcomes of persistent atrial fibrillation ablation.

BACKGROUND Rapid pulmonary vein (PV) activity has been shown to maintain paroxysmal atrial fibrillation (AF). We evaluated in persistent AF the cycle length (CL) gradient between PVs and the left atrium (LA) in an attempt to identify the subset of patients where PVs play an important role. METHODS AND RESULTS Ninety-seven consecutive patients undergoing first ablation for persistent AF were studied. For each PV, the CL of the fastest activation was assessed over 1 minute (PVfast) using Lasso recordings. The PV to LA CL gradient was quantified by the ratio of PVfast to LA appendage (LAA) AF CL. Stepwise ablation terminated AF in 73 patients (75%). In the AF termination group, the PVfast CL was much shorter than the LAA CL resulting in lower PVfast/LAA ratios compared with the nontermination group (71±10% versus 92±7%; P<0.001). Within the termination group, PVfast/LAA ratios were notably lower if AF terminated after PV isolation or limited adjunctive substrate ablation compared with patients who required moderate or extensive ablation (63±6% versus 75±8%; P<0.001). PVfast/LAA ratio <69% predicted AF termination after PV isolation or limited substrate ablation with 74% positive predictive value and 95% negative predictive value. After a mean follow-up of 29±17 months, freedom from arrhythmia recurrence off-antiarrhythmic drugs was achieved in most patients with PVfast/LAA ratios <69% as opposed to the remaining population (80% versus 43%; P<0.001). CONCLUSIONS The PV to LA CL gradient may identify the subset of patients in whom persistent AF is likely to terminate after PV isolation or limited substrate ablation and better long-term outcomes are achieved.

Positive braids of maximal signature

We characterise positive braid links with positive Seifert form via a finite number of forbidden minors. From this we deduce a one-to-one correspondence between prime positive braid links with positive Seifert form and simply laced Dynkin diagrams, as well as a simple classification of alternating positive braid knots.

Dispositional self-control capacity and trait anxiety as relates to coping styles

In the present article, we analyzed the relationship between dispositional self-control capacity, trait anxiety, and coping styles. Since self-control is often crucial for adapting one’s behavior to be positive, we predicted that dispositional differences in the capacity to exert self-control play a role in determining individuals coping styles. To test this assumption, we assessed participants’ (N = 163) dispositional self-control capacity using the Self-Control Scale, and their dispositional coping styles by using the short version of the German Coping Questionnaire SVF78 (German: Stressverarbeitungsfragebogen). A path analysis supported our hypothesis; higher levels of dispositional self-control capacity were positively associated with positive coping style and negatively associated with negative coping style. Basing on attentional control theory, we further assumed that this relationship was mediated by trait anxiety. In a second study based on a sample of N = 98 participants, we additionally applied the trait version of the State-Trait Anxiety Inventory. The results of a path analysis revealed that trait anxiety mediated the relationship between dispositional self-control capacity and coping styles. The results suggest that it may be useful to take a closer look at the role of self-control in the anxiety-coping relationship.

The Beach in Anglophone Literatures and Cultures: Reading Littoral Space

From early colonial encounters to the ecological disasters of the twenty-first century, the performativity of contact has been a crucial element in the political significance of the beach. Conceptualising the beach as a creative trope and as a socio-cultural site, as well as an aesthetically productive topography, this collection examines its multiplicity of meanings and functions as a natural environment engendering both desire and fear in the human imagination from the Victorian period to the present. The contributors examine literature, film, and art, in addition to moments of encounter and environmental crisis, to highlight the beach as a social space inspiring particular codes of behaviour and specific discourses, as a geographical frontier between land and water, as an historical site of contact and conflict, and as a vacationscape promising regeneration and withdrawal from everyday life. The diversity of the beach is reflected in the geographical range, with essays on locales and texts from Britain, Ireland, the Caribbean, South Africa, the United States, Polynesia, and New Zealand. Focusing on the changed function of the beach as a result of processes of industrialisation and the rise of a modern leisure and health culture, this interdisciplinary volume theorises the beach as a demarcater of the precarious boundary between land and the sea, as well as between nature and culture.

Gauged R-symmetry and its anomalies in 4D N=1 supergravity and phenomenological implications

We consider a class of models with gauged U(1) R symmetry in 4D N=1 super-gravity that have, at the classical level, a metastable ground state, an infinitesimally small (tunable) positive cosmological constant and a TeV gravitino mass. We analyse if these properties are maintained under the addition of visible sector (MSSM-like) and hidden sector state(s), where the latter may be needed for quantum consistency. We then discuss the anomaly cancellation conditions in supergravity as derived by Freedman, Elvang and Körs and apply their results to the special case of a U(1) R symmetry, in the presence of the Fayet-Iliopoulos term (ξ) and Green-Schwarz mechanism(s). We investigate the relation of these anomaly cancellation conditions to the “naive” field theory approach in global SUSY, in which case U(1) R cannot even be gauged. We show the two approaches give similar conditions. Their induced constraints at the phenomenological level, on the above models, remain strong even if one lifted the GUT-like conditions for the MSSM gauge couplings. In an anomaly-free model, a tunable, TeV-scale gravitino mass may remain possible provided that the U(1) R charges of additional hidden sector fermions (constrained by the cubic anomaly alone) do not conflict with the related values of U(1) R charges of their scalar superpartners, constrained by existence of a stable ground state. This issue may be bypassed by tuning instead the coefficients of the Kahler connection anomalies (b K , b CK ).

Examining Gender Differences in Received, Provided and Invisible Social Control: An Application of the Dual-Effects-Model

The dual-effects model of social control not only assumes that social control leads to better health practices but also arouses psychological distress. However, findings are inconsistent. The present study advances the current literature by examining social control from a dyadic perspective in the context of smoking. In addition, the study examines whether control, continuous smoking abstinence, and affect are differentially related for men and women. Before and three weeks after a self-set quit attempt, we examined 106 smokers (77 men, mean age: 40.67, average number of cigarettes smoked per day: 16.59 [SD=8.52, range=1-40] at baseline and 5.27 [SD=6.97, range=0-40] at follow-up) and their nonsmoking heterosexual partners, assessing received and provided control, continuous abstinence, and affect. With regard to smoker's affective reactions, partner's provided control was related to an increase in positive and to a decrease in negative affect, but only for female smokers. Moreover, the greater the discrepancy between smoker received and partner's provided control was the more positive affect increased and the more negative affect decreased, but again only for female smokers. These findings demonstrate that female smokers' well-being was raised over time if they were not aware of the control attempts of their nonsmoking partners, indicating positive effects of invisible social control. This study's results emphasize the importance of applying a dyadic perspective and taking gender differences in the dual-effects model of social control into account.

Which Radiographic Hip Parameters Do Not Have to Be Corrected for Pelvic Rotation and Tilt?

Background Acetabular anatomy on AP pelvic radiographsdepends on pelvic orientation during radiograph acquisition. However, not all parameters may change to a clinically relevant degree with differences in pelvic orientation. This issue may influence the diagnosis of acetabular pathologies and planning of corrective acetabular surgery (reorientation or rim trimming). However, to this point, it has not been well characterized. Questions/purposes We asked (1) which radiographic parameters change in a clinical setting when normalized to neutral pelvic orientation; (2) which parameters do not change in an experimental setting when the pelvis is experimentally rotated/tilted; and (3) which of these changes are ‘‘ultimately’’ relevant based on a prespecified definition of relevance. Methods In a clinical setup, 11 hip parameters were evaluated in 101 patients (126 hips) by two observers and the interobserver difference was calculated. All parameters were normalized to an anatomically defined neutral pelvic orientation with the help of a lateral pelvic radiograph and specific software. Differences between nonnormalized and normalized values were calculated (effect of normalization). In an experimental setup involving 20 cadaver pelves (40 hips), the maximum range for each parameter was computed with the pelvis rotated (range, −12° to 12°) and tilted (range, −24° to 24°). ‘‘Ultimately’’ relevant changes existed if the effect of normalization exceeded the interobserver difference (eg, 37% versus 6% for prevalence of a positive crossover sign) and/or the maximum experimental range exceeded 1 SD of interobserver difference (eg, 27% versus 6% for anterior acetabular coverage). Results In the clinical setup, all parameters except the ACM angle and craniocaudal acetabular coverage changed when being normalized, eg, effect of normalization for lateral center-edge angle, acetabular index, and sharp angle ranged from −5° to 4° (p values < 0.029). In the experimental setup, five parameters showed no major changes, whereas six parameters did change (all p values < 0.001). Ultimately relevant changes were found for anteroposterior acetabular coverage, retroversion index, and prevalence of a positive crossover or posterior wall sign. Conclusions Lateral center-edge angle, ACM angle, Sharp angle, acetabular and extrusion index, and craniocaudal acetabular coverage showed no relevant changes with varying pelvic orientation and can therefore be acquired independent from individual pelvic tilt and rotation in clinical practice. In contrast, anteroposterior acetabular coverage, crossover and posterior wall sign, and retroversion index call for specific efforts that address individual pelvic orientation such as computer-assisted evaluation of radiographs. Level of Evidence Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Desertification and Global Change: Innovative Management of Scarce Resources in Semi-Arid Areas. Experiences from development and research: Challenges for a better future

While most events related to the International Year of Deserts and Desertification 2006 took mainly a problem-oriented perspective and approach, the Bern Symposium held in May 2006 tried to adopt a more positive attitude by attempting to take stock of experience as well as best and worst practices in the past, both in development practice and in research. Through this deliberate focus on potentials, positive experiences, solutions and pathways, predominant passive and reactive attitudes and hopelessness might be better overcome. The Symposium was organized by CDE, NCCR North-South and Forum SLM.

Reliable LC3 and p62 autophagy marker detection in formalin fixed paraffin embedded human tissue by immunohistochemistry

Autophagy assures cellular homeostasis, and gains increasing importance in cancer, where it impacts on carcinogenesis, propagation of the malignant phenotype and development of resistance. To date, its tissue-based analysis by immunohistochemistry remains poorly standardized. Here we show the feasibility of specifically and reliably assessing the autophagy markers LC3B and p62 (SQSTM1) in formalin fixed and paraffin embedded human tissue by immunohistochemistry. Preceding functional experiments consisted of depleting LC3B and p62 in H1299 lung cancer cells with subsequent induction of autophagy. Western blot and immunofluorescence validated antibody specificity, knockdown efficiency and autophagy induction prior to fixation in formalin and embedding in paraffin. LC3B and p62 antibodies were validated on formalin fixed and paraffin embedded cell pellets of treated and control cells and finally applied on a tissue microarray with 80 human malignant and non-neoplastic lung and stomach formalin fixed and paraffin embedded tissue samples. Dot-like staining of various degrees was observed in cell pellets and 18/40 (LC3B) and 22/40 (p62) tumors, respectively. Seventeen tumors were double positive for LC3B and p62. P62 displayed additional significant cytoplasmic and nuclear staining of unknown significance. Interobserver-agreement for grading of staining intensities and patterns was substantial to excellent (kappa values 0.60 - 0.83). In summary, we present a specific and reliable IHC staining of LC3B and p62 on formalin fixed and paraffin embedded human tissue. Our presented protocol is designed to aid reliable investigation of dysregulated autophagy in solid tumors and may be used on large tissue collectives.

Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.

AIMS We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required.

Bovine Staphylococcus aureus: Subtyping, evolution, and zoonotic transfer.

Staphylococcus aureus is globally one of the most important pathogens causing contagious mastitis in cattle. Previous studies using ribosomal spacer (RS)-PCR, however, demonstrated in Swiss cows that Staph. aureus isolated from bovine intramammary infections are genetically heterogeneous, with Staph. aureus genotype B (GTB) and GTC being the most prominent genotypes. Furthermore, Staph. aureus GTB was found to be contagious, whereas Staph. aureus GTC and all the remaining genotypes were involved in individual cow disease. In addition to RS-PCR, other methods for subtyping Staph. aureus are known, including spa typing and multilocus sequence typing (MLST). They are based on sequencing the spa and various housekeeping genes, respectively. The aim of the present study was to compare the 3 analytic methods using 456 strains of Staph. aureus isolated from milk of bovine intramammary infections and bulk tanks obtained from 12 European countries. Furthermore, the phylogeny of animal Staph. aureus was inferred and the zoonotic transfer of Staph. aureus between cattle and humans was studied. The analyzed strains could be grouped into 6 genotypic clusters, with CLB, CLC, and CLR being the most prominent ones. Comparing the 3 subtyping methods, RS-PCR showed the highest resolution, followed by spa typing and MLST. We found associations among the methods but in many cases they were unsatisfactory except for CLB and CLC. Cluster CLB was positive for clonal complex (CC)8 in 99% of the cases and typically positive for t2953; it is the cattle-adapted form of CC8. Cluster CLC was always positive for t529 and typically positive for CC705. For CLR and the remaining subtypes, links among the 3 methods were generally poor. Bovine Staph. aureus is highly clonal and a few clones predominate. Animal Staph. aureus always evolve from human strains, such that every human strain may be the ancestor of a novel animal-adapted strain. The zoonotic transfer of IMI- and milk-associated strains of Staph. aureus between cattle and humans seems to be very limited and different hosts are not considered as a source for mutual, spontaneous infections. Spillover events, however, may happen.

Geochronology and isotope geochemistry of Eocene dykes intruding the Ladakh Batholith

In order to determine the extent and timing of dyke formation in the Ladakh Batholith we examined about 30 mostly andesitic dykes intruding the Ladakh batholith in a ca. 50 km wide area to the west of Leh (NW India). The dykes in the east of the area trend E-NE and those in the west trend N-NW. The difference in orientation is also evident in the petrography and isotopic signatures. The eastern dykes contain corroded quartz xenocrysts and show negative ε0(Nd) and positive ε0(Sr) values, where as the western dykes do not contain quartz xenocrysts and exhibit positive ε0(Nd) and near-zero ε0(Sr) values. The variability in Sr-Nd isotopes (ε0(Nd) = 3.6 to −9.6, ε0(Sr) = 0.4 to 143) and the quartz xenocrysts can best be explained by (differing degrees of) crustal assimilation of the parent magma of the dykes. Separated minerals from five dykes were dated by 40Ar-39Ar incremental heating: amphibole ages range between 50 and 54 Ma, and one biotite dated both by Rb-Sr and by 40Ar-39Ar gave an age of 45 Ma. One dated pseudotachylyte sample attests to brittle faulting at ca. 54 Ma. The combination of structural field evidence with petrographic, isotopic and geochronological analyses demonstrates that the dykes did not form from a single, progressively differentiating magma chamber, despite having formed in the same tectonic setting around the same time, and that processes such as crustal assimilation and magma mixing/mingling also played a significant role in magma petrogenesis.

Development of a rapid column-switching LC-MS/MS method for the quantification of THCCOOH and THCCOOH-glucuronide in whole blood for assessing cannabis consumption frequency

The concentration of 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THCCOOH) in whole blood is used as a parameter for assessing the consumption behavior of cannabis consumers. The blood level of THCCOOH-glucuronide might provide additional information about the frequency of cannabis use. To verify this assumption, a column-switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the rapid and direct quantification of free and glucuronidated THCCOOH in human whole blood was newly developed. The method comprised protein precipitation, followed by injection of the processed sample onto a trapping column and subsequent gradient elution to an analytical column for separation and detection. The total LC run time was 4.5 min. Detection of the analytes was accomplished by electrospray ionization in positive ion mode and selected reaction monitoring using a triple-stage quadrupole mass spectrometer. The method was fully validated by evaluating the following parameters: linearity, lower limit of quantification, accuracy and imprecision, selectivity, extraction efficiency, matrix effect, carry-over, dilution integrity, analyte stability, and re-injection reproducibility. All acceptance criteria were analyzed and the predefined criteria met. Linearity ranged from 5.0 to 500 μg/L for both analytes. The method was successfully applied to whole blood samples from a large collective of cannabis consumers, demonstrating its applicability in the forensic field.

Latent profiles of work motivation in adolescents in relation to work expectations, goal engagement, and changes in work experiences

Motivation plays a key role in successful entry into working life. Based on a cross-sectional and a one-year longitudinal study, we used a person-centered approach to explore work-related motivation (i.e., autonomous goals, positive affect, and occupational self-efficacy) among 577 students in 8th grade (Study 1) and 949 adolescents in vocational training (Study 2). Based on latent profile analysis, in both studies we identified four groups that were characterized by different levels of overall motivation and one group characterized by low positive affect and mean levels in autonomous goals and self-efficacy. Profiles characterized by high levels of motivation showed the highest levels of positive work expectations and goal engagement and the lowest levels of negative work expectations in Study 1 and the highest levels of person-job fit, work engagement, and job satisfaction in Study 2. Moreover, latent difference score analysis showed that motivational profiles predicted changes in person-job fit and work engagement across one year but not in job satisfaction. The results imply that career counselors should be aware of characteristic motivational patterns of clients that may require specific counseling approaches.