European experience on the practical use of levosimendan in patients with acute heart failure syndromes

The novel calcium sensitizer and ATP-dependent potassium channel opener levosimendan has been introduced for routine use in several European countries. Recent reports on clinical experience confirm the positive hemodynamic results and beneficial clinical effects described in the initial dose-finding and randomized comparative therapeutic trials in patients with severe low-output heart failure. In addition, studies in small series of patients with cardiogenic shock after myocardial infarction and/or surgical interventions and post-interventional myocardial dysfunction (stunning) indicate that the inotropic and vasodilating actions of levosimendan may be of value in a wider range of indications. Dose recommendations, combination with other drugs, and potential side effects are discussed in this overview

Natural history of fetal pyelocaliectasia

INTRODUCTION: It is estimated that genitourinary anomalies comprise 20% of all antenatally detected fetal anomalies, and pyelocaliectasia is the most common one. Detection of antenatal dilatation of the urinary tract does not always indicate postnatal urinary tract obstruction or even a significant genitourinary anomaly. Most cases will improve spontaneously, representing a temporary physiologic impedence and do not require surgery. MATERIALS AND METHODS: In a two-year period we studied 197 newborns, with prenatal pyelocaliectasia, without concomitant anomaly, delivered at Maternidade Dr. Daniel de Matos. In the postnatal follow-up period, the infants were followed at Pediatrics Department, at our Center. RESULTS: A male predilection was found. Ultrasonic follow-up of the 197 infants showed that pyelocaliectasia resolved in 97%, while 3% still presented it in the postnatal ultrasound. Complementary renal evaluation, with voiding cystourethrography and radionuclide imaging, was realised in 29 (15%) infants to further characterize the abnormality detected in postnatal ultrasound. Surgery was performed in four (2%) children. CONCLUSION: Prenatally diagnosed pyelocaliectasia may be safely observed, and surgical correction should be performed only if renal compromise occurs

Calabi-Yau Orbifolds and Torus Coverings

The theory of coverings of the two-dimensional torus is a standard part of algebraic topology and has applications in several topics in string theory, for example, in topological strings. This paper initiates applications of this theory to the counting of orbifolds of toric Calabi-Yau singularities, with particular attention to Abelian orbifolds of C^D. By doing so, the work introduces a novel analytical method for counting Abelian orbifolds, verifying previous algorithm results. One identifies a p-fold cover of the torus T^{D-1} with an Abelian orbifold of the form C^D/Z_p, for any dimension D and a prime number p. The counting problem leads to polynomial equations modulo p for a given Abelian subgroup of S_D, the group of discrete symmetries of the toric diagram for C^D. The roots of the polynomial equations correspond to orbifolds of the form C^D/Z_p, which are invariant under the corresponding subgroup of S_Ds. In turn, invariance under this subgroup implies a discrete symmetry for the corresponding quiver gauge theory, as is clearly seen by its brane tiling formulation.Comment: 33 pages, 5 figures, 7 tables; version published on JHE

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI

Generalising unit-refutation completeness and SLUR via nested input resolution

We introduce two hierarchies of clause-sets, SLUR_k and UC_k, based on the classes SLUR (Single Lookahead Unit Refutation), introduced in 1995, and UC (Unit refutation Complete), introduced in 1994. The class SLUR, introduced in [Annexstein et al, 1995], is the class of clause-sets for which unit-clause-propagation (denoted by r_1) detects unsatisfiability, or where otherwise iterative assignment, avoiding obviously false assignments by look-ahead, always yields a satisfying assignment. It is natural to consider how to form a hierarchy based on SLUR. Such investigations were started in [Cepek et al, 2012] and [Balyo et al, 2012]. We present what we consider the "limit hierarchy" SLUR_k, based on generalising r_1 by r_k, that is, using generalised unit-clause-propagation introduced in [Kullmann, 1999, 2004]. The class UC, studied in [Del Val, 1994], is the class of Unit refutation Complete clause-sets, that is, those clause-sets for which unsatisfiability is decidable by r_1 under any falsifying assignment. For unsatisfiable clause-sets F, the minimum k such that r_k determines unsatisfiability of F is exactly the "hardness" of F, as introduced in [Ku 99, 04]. For satisfiable F we use now an extension mentioned in [Ansotegui et al, 2008]: The hardness is the minimum k such that after application of any falsifying partial assignments, r_k determines unsatisfiability. The class UC_k is given by the clause-sets which have hardness <= k. We observe that UC_1 is exactly UC. UC_k has a proof-theoretic character, due to the relations between hardness and tree-resolution, while SLUR_k has an algorithmic character. The correspondence between r_k and k-times nested input resolution (or tree resolution using clause-space k+1) means that r_k has a dual nature: both algorithmic and proof theoretic. This corresponds to a basic result of this paper, namely SLUR_k = UC_k.Comment: 41 pages; second version improved formulations and added examples, and more details regarding future directions, third version further examples, improved and extended explanations, and more on SLUR, fourth version various additional remarks and editorial improvements, fifth version more explanations and references, typos corrected, improved wordin

Correlates of comorbid anxiety and externalizing disorders in childhood obsessive compulsive disorder

The present study examines the influence of diagnostic comorbidity on the demographic, psychiatric, and functional status of youth with a primary diagnosis of obsessive compulsive disorder (OCD). Two hundred and fifteen children (ages 5–17) referred to a university-based OCD specialty clinic were compared based on DSM-IV diagnostic profile: OCD without comorbid anxiety or externalizing disorder, OCD plus anxiety disorder, and OCD plus externalizing disorder. No age or gender differences were found across groups. Higher OCD severity was found for the OCD + ANX group, while the OCD + EXT group reported greater functional impairment than the other two groups. Lower family cohesion was reported by the OCD + EXT group compared to the OCD group and the OCD + ANX group reported higher family conflict compared to the OCD + EXT group. The OCD + ANX group had significantly lower rates of tic disorders while rates of depressive disorders did not differ among the three groups. The presence of comorbid anxiety and externalizing psychopathology are associated with greater symptom severity and functional and family impairment and underscores the importance of a better understanding of the relationship of OCD characteristics and associated disorders. Results and clinical implications are further discussed

10 simple rules to create a serious game, illustrated with examples from structural biology

Serious scientific games are games whose purpose is not only fun. In the field of science, the serious goals include crucial activities for scientists: outreach, teaching and research. The number of serious games is increasing rapidly, in particular citizen science games, games that allow people to produce and/or analyze scientific data. Interestingly, it is possible to build a set of rules providing a guideline to create or improve serious games. We present arguments gathered from our own experience ( Phylo , DocMolecules , HiRE-RNA contest and Pangu) as well as examples from the growing literature on scientific serious games

Flavor of quiver-like realizations of effective supersymmetry

We present a class of supersymmetric models which address the flavor puzzle and have an inverted hierarchy of sfermions. Their construction involves quiver-like models with link fields in generic representations. The magnitude of Standard-Model parameters is obtained naturally and a relatively heavy Higgs boson is allowed without fine tuning. Collider signatures of such models are possibly within the reach of LHC in the near future.Comment: LaTeX, 17 pages, 3 figures. V2: reference adde