Zeta function regularization for a scalar field in a compact domain

We express the zeta function associated to the Laplacian operator on $S^1_r\times M$ in terms of the zeta function associated to the Laplacian on $M$, where $M$ is a compact connected Riemannian manifold. This gives formulas for the partition function of the associated physical model at low and high temperature for any compact domain $M$. Furthermore, we provide an exact formula for the zeta function at any value of $r$ when $M$ is a $D$-dimensional box or a $D$-dimensional torus; this allows a rigorous calculation of the zeta invariants and the analysis of the main thermodynamic functions associated to the physical models at finite temperature.Comment: 19 pages, no figures, to appear in J. Phys.

Radiocarbon Evidence for the Importance of Surface Vegetation on Fermentation and Methanogenesis in Contrasting Types of Boreal Peatlands

We found a consistent distribution pattern for radiocarbon in dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), and methane replicated across spatial and temporal scales in northern peatlands from Minnesota to Alaska. The 14C content of DOC is relatively modern throughout the peat column, to depths of 3 m. In sedge-dominated peatlands, the 14C contents of the products of respiration, CH4 and DIC, are essentially the same and are similar to that of DOC. In Sphagnum- and woody plant-dominated peatlands with few sedges, however, the respiration products are similar but intermediate between the 14C contents of the solid phase peat and the DOC. Preliminary data indicates qualitative differences in the pore water DOC, depending on the extent of sedge cover, consistent with the hypothesis that the DOC in sedge-dominated peatlands is more reactive than DOC in peatlands where Sphagnum or other vascular plants dominate. These data are supported by molecular level analysis of DOC by ultrahigh-resolution mass spectrometry that suggests more dramatic changes with depth in the composition of DOC in the sedge-dominated peatland pore waters relative to changes observed in DOC where Sphagnum dominates. The higher reactivity of DOC from sedge-dominated peatlands may be a function of either different source materials or environmental factors that are related to the abundance of sedges in peatlands

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Saints and lovers: myths of the avant-garde in Michel Georges-Michel's Les Montparnos

This article examines Michel Georges-Michel’s 1924 novel Les Montparnos as a study of the myths circulating around the Montparnasse avant-garde of the 1920s, and their function in relation to art. Key amongst these myths is the idea of art as a religion, according to which avant-garde artists are conceived as secular saints and martyrs. While this notion of artist as saint is strongly present in early-twentieth-century biographies of Van Gogh, Georges-Michel explicitly relates his fictionalized version of Modigliani’s life not to such recent models but rather to the Renaissance masters, and especially to Raphael, a link which is explained in terms of the post-war ‘retour à l’ordre’ in French artistic culture. The novel’s references to Raphael as archetypal painter-lover are also related to its construction of a myth of the artist as virile and sexually prolific, and to its identification of creative and sexual impulses

The Critique of Scholastic Language in Renaissance Humanism and Early Modern Philosophy

This article studies some key moments in the long tradition of the critiqueof scholastic language, voiced by humanists and early-modern philosophers alike. It aims at showing how the humanist idiom of “linguistic usage,” “convention,” “custom,” “common” and “natural” language, and “everyday speech” was repeated and put to new use by early-modern philosophers in their own critique of scholastic language. Focusing on Valla, Vives, Sanches, Gassendi, Hobbes, and Leibniz, the article shows that all these thinkers shared a conviction that scholastic language, at least in its more baroque forms, was artificial, unnatural, uninformative, ungrammatical, and quasi-precise. The scholastics were accused of having introduced a terminology that was a far cry from the common language people spoke, wrote, and read. But what was meant by “common language” and such notions? They were not so easy to define. For the humanists, it meant the Latin of the great classical authors, but this position, as the article suggests, had its tensions. In the later period it became even more difficult to give positive substance to these notions, as the world became, linguistically speaking, increasingly more pluralistic. Yet the attack on scholasticlanguage continued to be conducted in these terms. The article concludes that the long road of what we may call the democratization of philosophical language, so dear to early-modern philosophers, had its roots – ironically perhaps – in the humanist return to classical Latin as the common language

The experience of admission to psychiatric hospital among Chinese adult patients in Hong Kong

<p>Abstract</p> <p>Background</p> <p>The paper reports on a study to evaluate the psychometric properties and cultural appropriateness of the Chinese translation of the Admission Experience Survey (AES).</p> <p>Methods</p> <p>The AES was translated into Chinese and back-translated. Content validity was established by focus groups and expert panel review. The Chinese version of the Admission Experience Survey (C-AES) was administered to 135 consecutively recruited adult psychiatric patients in the Castle Peak Hospital (Hong Kong SAR, China) within 48 hours of admission. Construct validity was assessed by comparing the scores from patients admitted voluntarily versus patients committed involuntarily, and those received physical or chemical restraint versus those who did not. The relationship between admission experience and psychopathology was examined by correlating C-AES scores with the Brief Psychiatric Rating Scale (BPRS) scores.</p> <p>Results</p> <p>Spearman's item-to-total correlations of the C-AES ranged from 0.50 to 0.74. Three factors from the C-AES were extracted using factor analysis. Item 12 was omitted because of poor internal consistency and factor loading. The factor structure of the Process Exclusion Scale (C-PES) corresponded to the English version, while some discrepancies were noted in the Perceived Coercion Scale (C-PCS) and the Negative Pressure Scale (C-NPS). All subscales had good internal consistencies. Scores were significantly higher for patients either committed involuntarily or subjected to chemical or physical restrain, independent on severity of psychotic symptoms.</p> <p>Conclusion</p> <p>The Chinese AES is a psychometrically sound instrument assessing the three different aspects of the experience of admission, namely "negative pressure, "process exclusion" and "perceived coercion". The potential of C-AES in exploring subjective experience of psychiatric admission and effects on treatment adherence should be further explored.</p

Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen

Author manuscript: 2010 September 22.Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers[superscript 1, 2]. The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag- and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinas—an organ that critically requires cyclin D1 function[superscript 3, 4]—cyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1-/-) retinas. Transduction of an activated allele of Notch1 into Ccnd1-/- retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term ‘genetic–proteomic’, can be used to study the in vivo function of essentially any protein

Mothers Matter Too: Benefits of Temperature Oviposition Preferences in Newts

The maternal manipulation hypothesis states that ectothermic females modify thermal conditions during embryonic development to benefit their offspring (anticipatory maternal effect). However, the recent theory suggests that the ultimate currency of an adaptive maternal effect is female fitness that can be maximized also by decreasing mean fitness of individual offspring. We evaluated benefits of temperature oviposition preferences in Alpine newts (Ichthyosaura [formerly Triturus] alpestris) by comparing the thermal sensitivity of maternal and offspring traits across a range of preferred oviposition temperatures (12, 17, and 22°C) and by manipulating the egg-predation risk during oviposition in a laboratory thermal gradient (12–22°C). All traits showed varying responses to oviposition temperatures. Embryonic developmental rates increased with oviposition temperature, whereas hatchling size and swimming capacity showed the opposite pattern. Maternal oviposition and egg-predation rates were highest at the intermediate temperature. In the thermal gradient, females oviposited at the same temperature despite the presence of caged egg-predators, water beetles (Agabus bipustulatus). We conclude that female newts prefer a particular temperature for egg-deposition to maximize their oviposition performance rather than offspring fitness. The evolution of advanced reproductive modes, such as prolonged egg-retention and viviparity, may require, among others, the transition from selfish temperature preferences for ovipositon to the anticipatory maternal effect