Real world experience of response to pirfenidone in patients with idiopathic pulmonary fibrosis: a two centre retrospective study.

Introduction: Pirfenidone has been shown to reduce the decline in forced vital capacity (FVC) compared to placebo in patients with idiopathic pulmonary fibrosis (IPF). Previous studies have suggested that patients with a more rapid decline in FVC during the period before starting pirfenidone experience the greatest benefit from treatment. The purpose of this retrospective observational study was to investigate the response to pirfenidone in IPF patients, comparing two groups stratified by the annual rate of decline in FVC % predicted prior to treatment. Methods: Using the rate of decline in FVC % predicted in the 12 months prior to pirfenidone, patients were stratified into slow (<5%) or rapid (≥5%) decliner groups. Comparisons in the lung function response to pirfenidone in these two groups were performed. Results: Pirfenidone resulted in no statistically significant reduction in the median annual rate of decline in FVC or FVC % predicted. In the rapid decliners, pirfenidone significantly reduced the median (IQR) annual rate of decline in FVC % predicted (-8.7 (-14.2 - -7.0) %/yr vs 2.0 (-7.1 - 6.0) %/yr; n=17; p<0.01). In the slow decliners, pirfenidone did not reduce the median (IQR) annual rate of decline in FVC % predicted (-1.3 (-3.2 - 1.3) %/yr vs -5.0 (-8.3 - -0.35) %/yr; n=17; p=0.028). Conclusions: We demonstrate the greater net effect of pirfenidone in IPF patients declining rapidly. We suggest that using an annual rate of decline in FVC of <5% and ≥5% may be useful in counselling patients with regard to pirfenidone treatment

Pair Production of small Black Holes in Heterotic String Theories

We study pair production of small BPS BH's in heterotic strings compactified on tori and in the FHSV model. After recalling the identification of small BH's in the perturbative BPS spectrum, we compute the tree-level amplitudes for processes initiated by massless vector bosons or gravitons. We then analyze the resulting cross sections in terms of energy and angular distributions. Finally, we briefly comment on scenari with large extra dimensions and on generalizations of our results to non-BPS, non-extremal and rotating BH's.Comment: 33 page

Populating the swampland: the case of U(1)^496 and E_8 x U(1)^248

For d=10 N=1 SUGRA coupled to d=10 N=1 SYM, anomaly cancellation places severe constraints on the allowed gauge groups. Besides the ones known to appear in string theory, only U(1)^496 and E_8 x U(1)^248 are allowed. There are no known theories of quantum gravity that reduce in some limit to these two last supergravity theories, and in this note I present some evidence that those quantum theories might not exist. The first observation is that, upon compactification, requring that the quantum theory possesses a moduli space with finite volume typically implies the existence of singularities where the 4d gauge group is enhanced, but for these two theories that gauge enhancement is problematic from the 10d point of view. I also point out that while these four supergravity theories present repulson-type singularities, the known mechanism that repairs those singularities for the first two - the non-Abelian enhancon - is not available for the last two theories. In short, these two supergravity theories might be too Abelian for their own good.Comment: 12 page

Prevalence of human papillomavirus in young Italian women with normal cytology: how should we adapt the national vaccination policy?

Background: Human Papillomavirus (HPV) is the most common sexually transmitted infection. In Italy, HPV vaccination is now offered free of charge to 12-year-old females. However, some regional health authorities have extended free vaccination to other age-groups, especially to girls under 18 years of age. We conducted a multicentre epidemiological study to ascertain the prevalence of different genotypes of HPV in young Italian women with normal cytology, with the aim of evaluating the possibility of extending vaccination to older females.Methods: The study was performed in 2010. Women aged 16-26 years with normal cytology were studied. Cervical samples were analyzed to identify the presence of HPV by PCR amplification of a segment of ORF L1 (450 bp). All positive HPV-DNA samples underwent viral genotype analysis by means of a restriction fragment length polymorphism assay.Results: Positivity for at least one HPV genotype was found in 18.2% of the 566 women recruited: 48.1% in the 16-17 age-class, 15.4 in the 18-20 age-class, 21.9% in the 21-23 age-class, and 15.5% in the 24-26 age-class; 10.1% of women were infected by at least one high-risk HPV genotype. HPV-16 was the most prevalent genotype. Only 4 (0.7%), 4 (0.7%) and 3 (0.5%) women were infected by HPV-18, HPV-6 and HPV-11, respectively. Of the HPV-DNA-positive women, 64.1% presented only one viral genotype, while 24.3% had multiple infections. The HPV genotypes most often involved in multiple infections were high-risk. A high prevalence was noted in the first years of sexual activity (48.1% of HPV-DNA-positive women aged 16-17 years); HPV prevalence subsequently declined and stabilized.The estimate of cumulative proportions of young women free from any HPV infection at each age was evaluated; 93.3% and 97.1% of 26 year-old women proved free from HPV-16 and/or HPV-18 and from HPV-6 and/or HPV-11, respectively.Conclusions: Our findings confirm the crucial importance of conducting studies on women without cytological damage, in order to optimise and up-date preventive interventions against HPV infection, and suggest that vaccinating 26-year-old females at the time of their first pap-test is to be recommend, though this issue should be further explored

Hermitian Yang-Mills instantons on resolutions of Calabi-Yau cones

We study the construction of Hermitian Yang-Mills instantons over resolutions of Calabi-Yau cones of arbitrary dimension. In particular, in d complex dimensions, we present an infinite family, parametrised by an integer k and a continuous modulus, of SU(d) instantons. A detailed study of their properties, including the computation of the instanton numbers is provided. We also explain how they can be used in the construction of heterotic non-Kahler compactifications.Comment: 20 pages, 1 figure; typos corrected, section 3.1 expande

SU(5) D-brane realizations, Yukawa couplings and proton stability

We discuss SU(5) Grand Unified Theories in the context of orientifold compactifications. Specifically, we investigate two and three D-brane stack realizations of the Georgi-Glashow and the flipped SU(5) model and analyze them with respect to their Yukawa couplings. As pointed out in arXiv:0909.0271 the most economical Georgi-Glashow realization based on two stacks generically suffers from a disastrous large proton decay rate. We show that allowing for an additional U(1) D-brane stack this as well as other phenomenological problems can be resolved. We exemplify with globally consistent Georgi-Glashow models based on RCFT that these D-brane quivers can be indeed embedded in a global setting. These globally consistent realizations admit rigid O(1) instantons inducing the perturbatively missing coupling 10105^H. Finally we show that flipped SU(5) D-brane realizations even with multiple U(1) D-brane stacks are plagued by severe phenomenological drawbacks which generically cannot be overcome.Comment: 34 pages v2 minor correction

Fjords as Aquatic Critical Zones (ACZs)

In recent decades, the land-ocean aquatic continuum, commonly defined as the interface, or transition zone, between terrestrial ecosystems and the open ocean, has undergone dramatic changes. On-going work has stressed the importance of treating Aquatic Critical Zones (ACZs) as a sensitive system needing intensive investigation. Here, we discuss fjords as an ACZ in the context of sedimentological, geochemical, and climatic impacts. These diverse physical features of fjords are key in controlling the sources, transport, and burial of organic matter in the modern era and over the Holocene. High sediment accumulation rates in fjord sediments allow for high-resolution records of past climate and environmental change where multiple proxies can be applied to fjord sediments that focus on either marine or terrestrial-derived components. Humans through land-use change and climatic stressors are having an impact on the larger carbon stores in fjords. Sediment delivery whether from accelerating erosion (e.g. mining, deforestation, road building, agriculture) or from sequestration of fluvial sediment behind dams has been seriously altered in the Anthropocene. Climate change affecting rainfall and river discharge into fjords will impact the thickness and extent of the low-salinity layer in the upper reaches of the fjord, slowing the rate of the overturning circulation and deep-water renewal – thereby impacting bottom water oxygen concentrations

Anti-asthma medication prescribing to children in the Lombardy Region of Italy: chronic versus new users

<p>Abstract</p> <p>Background</p> <p>Although anti-asthma medications are amongst those most frequently under or over prescribed it is generally accepted that prescriptions for such agents can be used as a proxy for disease prevalence. The aims of this study were to estimate prevalence and incidence of childhood asthma in a representative Italian area by analysing three years of anti-asthmatic prescriptions and hospitalizations of subjects with chronic or first time treatment, and to underline appropriateness of therapeutic choices.</p> <p>Methods</p> <p>The analysis involved prescriptions given to 6-17 year olds between 2003 and 2005 in Italy's Lombardy Region. The youths were classified as potential asthmatics, based on the different degree of drug utilization: occasional, low or high users, and grouped as 'new onset' or 'chronic' cases based on the duration of therapy dispensed. The analysis of prescriptions and hospitalization rate of these groups provided an estimate of the 2005 asthma prevalence and incidence and allowed an estimation of the level of appropriateness of treatments.</p> <p>Results</p> <p>During 2005, the estimated incidence of potential asthmatics was 0.8% and the estimated prevalence was 3.5%. When viewed retrospectively for two years, records showed that 47% of potential asthmatics received prescriptions also during 2004 and 30% also during 2003. During the three years considered, 7.5%, 2.8%, and 1.5% of high, low, and occasional users, respectively, were hospitalized for asthma. The most important inappropriateness found was the prescription of long acting beta adrenergics as first time treatment.</p> <p>Conclusions</p> <p>This study allowed a proxy of asthma incidence, prevalence, and severity. The analyses highlighted a low compliance with the guidelines, suggesting that educational interventions are needed to obtain a more rational management of childhood asthma, especially in subjects starting therapy.</p

Can disordered mobile phone use be considered a behavioral addiction? An update on current evidence and a comprehensive model for future research

Despite the many positive outcomes, excessive mobile phone use is now often associated with potentially harmful and/or disturbing behaviors (e.g., symptoms of deregulated use, negative impact on various aspects of daily life such as relationship problems, and work intrusion). Problematic mobile phone use (PMPU) has generally been considered as a behavioral addiction that shares many features with more established drug addictions. In light of the most recent data, the current paper reviews the validity of the behavioral addiction model when applied to PMPU. On the whole, it is argued that the evidence supporting PMPU as an addictive behavior is scarce. In particular, it lacks studies that definitively show behavioral and neurobiological similarities between mobile phone addiction and other types of legitimate addictive behaviors. Given this context, an integrative pathway model is proposed that aims to provide a theoretical framework to guide future research in the field of PMPU. This model highlights that PMPU is a heterogeneous and multi-faceted condition