A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144

A meta-analysis of two randomised trials of early chemotherapy in asymptomatic metastatic colorectal cancer

This report constitutes a prospectively planned meta-analysis combining two almost identical trials undertaken in Australasia and Canada to study the effect of starting chemotherapy immediately in asymptomatic patients with metastatic colorectal cancer. Patients (n=168) were randomised to receive either immediate or delayed treatment (at onset of predefined symptoms). Australasian patients received either weekly 5-fluorouracil and leucovorin (500 and 20 mg m−2, respectively) (n=59) or the daily × 5 Mayo Clinic schedule (425 and 20 mg m−2, respectively) (n=42). Canadian patients were treated with the Mayo schedule (n=67). Otherwise, the two studies were almost identical in design and each used the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 instrument for measuring quality of life (QoL). Treatment was continued until 6 months had elapsed or disease progression occurred. Low accrual led to trial suspension before the predetermined sample size for either study was reached. Median survival was not significantly better with immediate treatment (median 13.0 vs 11.0 months; hazard ratio, 1.15; 95% confidence interval (CI) 0.79–1.72; P=0.49). There was no statistically significant difference in progression-free survival (time from randomisation until first evidence of progression after chemotherapy, 10.2 vs 10.8 months; hazard ratio, 1.08; 95% CI 0.71–1.64; P=0.73). There was no difference in overall QoL or its individual domains between the two treatment strategies at baseline or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved QoL compared to withholding treatment until symptoms occurred

The Hubbard model within the equations of motion approach

The Hubbard model has a special role in Condensed Matter Theory as it is considered as the simplest Hamiltonian model one can write in order to describe anomalous physical properties of some class of real materials. Unfortunately, this model is not exactly solved except for some limits and therefore one should resort to analytical methods, like the Equations of Motion Approach, or to numerical techniques in order to attain a description of its relevant features in the whole range of physical parameters (interaction, filling and temperature). In this manuscript, the Composite Operator Method, which exploits the above mentioned analytical technique, is presented and systematically applied in order to get information about the behavior of all relevant properties of the model (local, thermodynamic, single- and two- particle ones) in comparison with many other analytical techniques, the above cited known limits and numerical simulations. Within this approach, the Hubbard model is shown to be also capable to describe some anomalous behaviors of the cuprate superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells

<p>Abstract</p> <p>Background</p> <p>All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human β-defensin 2 is the most potent molecule and is inducible by exposure to inflammatory stimuli such as bacterial components or proinflammatory cytokines. Even though the β-defensin 2 is an important AIIM, the induction mechanism of this molecule has not been clearly established. We believe that this report is the first attempt to elucidate NTHi induced β-defensin expression in airway mucosa, which includes the middle ear.</p> <p>Methods</p> <p>Monoclonal antibody blocking method was employed in monitoring the TLR-dependent NTHi response. Two gene knock down methods – dominant negative (DN) plasmid and small interfering RNA (siRNA) – were employed to detect and confirm the involvement of several key genes in the signaling cascade resulting from the NTHi stimulated β-defensin 2 expression in human middle ear epithelial cell (HMEEC-1). The student's <it>t</it>-test was used for the statistical analysis of the data.</p> <p>Results</p> <p>The experimental results showed that the major NTHi-specific receptor in HMEEC-1 is the Toll-like receptor 2 (TLR2). Furthermore, recognition of NTHi component(s)/ligand(s) by TLR2, activated the Toll/IL-1 receptor (TIR)-MyD88-IRAK1-TRAF6-MKK3/6-p38 MAPK signal transduction pathway, ultimately leading to the induction of β-defensin 2.</p> <p>Conclusion</p> <p>This study found that the induction of β-defensin 2 is highest in whole cell lysate (WCL) preparations of NTHi, suggesting that the ligand(s) responsible for this up-regulation may be soluble macromolecule(s). We also found that this induction takes place through the TLR2 dependent MyD88-IRAK1-TRAF6-p38 MAPK pathway, with the primary response occurring within the first hour of stimulation. In combination with our previous studies showing that IL-1α-induced β-defensin 2 expression takes place through a MyD88-independent Raf-MEK1/2-ERK MAPK pathway, we found that both signaling cascades act synergistically to up-regulate β-defensin 2 levels. We propose that this confers an essential evolutionary advantage to the cells in coping with infections and may serve to amplify the innate immune response through paracrine signaling.</p

The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants

BACKGROUND: Late onset sepsis is a frequent complication of prematurity associated with increased mortality and morbidity. The commensal bacteria of the gastrointestinal tract play a key role in the development of healthy immune responses. Healthy term infants acquire these commensal organisms rapidly after birth. However, colonisation in preterm infants is adversely affected by delivery mode, antibiotic treatment and the intensive care environment. Altered microbiota composition may lead to increased colonisation with pathogenic bacteria, poor immune development and susceptibility to sepsis in the preterm infant.Probiotics are live microorganisms, which when administered in adequate amounts confer health benefits on the host. Amongst numerous bacteriocidal and nutritional roles, they may also favourably modulate host immune responses in local and remote tissues. Meta-analyses of probiotic supplementation in preterm infants report a reduction in mortality and necrotising enterocolitis. Studies with sepsis as an outcome have reported mixed results to date.Allergic diseases are increasing in incidence in "westernised" countries. There is evidence that probiotics may reduce the incidence of these diseases by altering the intestinal microbiota to influence immune function. METHODS/DESIGN: This is a multi-centre, randomised, double blinded, placebo controlled trial investigating supplementing preterm infants born at < 32 weeks' gestation weighing < 1500 g, with a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis). A total of 1,100 subjects are being recruited in Australia and New Zealand. Infants commence the allocated intervention from soon after the start of feeds until discharge home or term corrected age. The primary outcome is the incidence of at least one episode of definite (blood culture positive) late onset sepsis before 40 weeks corrected age or discharge home. Secondary outcomes include: Necrotising enterocolitis, mortality, antibiotic usage, time to establish full enteral feeds, duration of hospital stay, growth measurements at 6 and 12 months' corrected age and evidence of atopic conditions at 12 months' corrected age. DISCUSSION: Results from previous studies on the use of probiotics to prevent diseases in preterm infants are promising. However, a large clinical trial is required to address outstanding issues regarding safety and efficacy in this vulnerable population. This study will address these important issues. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415The product "ABC Dophilus Probiotic Powder for Infants®", Solgar, USA has its 3 probiotics strains registered with the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ--German Collection of Microorganisms and Cell Cultures) as BB-12 15954, B-02 96579, Th-4 15957

Season of Birth and Dopamine Receptor Gene Associations with Impulsivity, Sensation Seeking and Reproductive Behaviors

Season of birth (SOB) has been associated with many physiological and psychological traits including novelty seeking and sensation seeking. Similar traits have been associated with genetic polymorphisms in the dopamine system. SOB and dopamine receptor genetic polymorphisms may independently and interactively influence similar behaviors through their common effects on the dopaminergic system.Based on a sample of 195 subjects, we examined whether SOB was associated with impulsivity, sensation seeking and reproductive behaviors. Additionally we examined potential interactions of dopamine receptor genes with SOB for the same set of traits. Phenotypes were evaluated using the Sociosexual Orientation Inventory, the Barratt Impulsivity Scale, the Eysenck Impulsivity Questionnaire, the Sensation Seeking Scale, and the Delay Discounting Task. Subjects were also asked about their age at first sex as well as their desired age at the birth of their first child. The dopamine gene polymorphisms examined were Dopamine Receptor D2 (DRD2) TaqI A and D4 (DRD4) 48 bp VNTR. Primary analyses included factorial genderxSOB ANOVAs or binary logistic regression models for each dependent trait. Secondary analysis extended the factorial models by also including DRD2 and DRD4 genotypes as independent variables. Winter-born males were more sensation seeking than non-winter born males. In factorial models including both genotype and season of birth as variables, two previously unobserved effects were discovered: (1) a SOBxDRD4 interaction effect on venturesomeness and (2) a DRD2xDRD4 interaction effect on sensation seeking.These results are consistent with past findings that SOB is related to sensation seeking. Additionally, these results provide tentative support for the hypothesis that SOB modifies the behavioral expression of dopaminergic genetic polymorphism. These findings suggest that SOB should be included in future studies of risky behaviors and behavioral genetic studies of the dopamine system

Evidence-based guidelines for use of probiotics in preterm neonates

<p>Abstract</p> <p>Background</p> <p>Current evidence indicates that probiotic supplementation significantly reduces all-cause mortality and definite necrotising enterocolitis without significant adverse effects in preterm neonates. As the debate about the pros and cons of routine probiotic supplementation continues, many institutions are satisfied with the current evidence and wish to use probiotics routinely. Because of the lack of detail on many practical aspects of probiotic supplementation, clinician-friendly guidelines are urgently needed to optimise use of probiotics in preterm neonates.</p> <p>Aim</p> <p>To develop evidence-based guidelines for probiotic supplementation in preterm neonates.</p> <p>Methods</p> <p>To develop core guidelines on use of probiotics, including strain selection, dose and duration of supplementation, we primarily used the data from our recent updated systematic review of randomised controlled trials. For equally important issues including strain identification, monitoring for adverse effects, product format, storage and transport, and regulatory hurdles, a comprehensive literature search, covering the period 1966-2010 without restriction on the study design, was conducted, using the databases PubMed and EMBASE, and the proceedings of scientific conferences; these data were used in our updated systematic review.</p> <p>Results</p> <p>In this review, we present guidelines, including level of evidence, for the practical aspects (for example, strain selection, dose, duration, clinical and laboratory surveillance) of probiotic supplementation, and for dealing with non-clinical but important issues (for example, regulatory requirements, product format). Evidence was inadequate in some areas, and these should be a target for further research.</p> <p>Conclusion</p> <p>We hope that these evidence-based guidelines will help to optimise the use of probiotics in preterm neonates. Continued research is essential to provide answers to the current gaps in knowledge about probiotics.</p

Emerging roles of ATF2 and the dynamic AP1 network in cancer

Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lau, Eric . Burnham Institute for Medical Research; Estados UnidosFil: Ronai, Zeev . Burnham Institute for Medical Research; Estados Unido