Two ways to be endemic. Alps and Apennines are different functional refugia during climatic cycles

Endemics co-occur because they evolved in situ and persist regionally or because they evolved ex situ and later dispersed to shared habitats, generating evolutionary or ecological endemicity centres, respectively. We investigate whether different endemicity centres can intertwine in the region ranging from Alps to Sicily, by studying their butterfly fauna. We gathered an extensive occurrence data set for butterflies of the study area (27,123 records, 269 species, in cells of 0.5 × 0.5 degrees of latitude-longitude). We applied molecular-based delimitation methods (GMYC model) to 26,557 cytochrome c oxidase subunit 1 (COI) sequences of Western Palearctic butterflies. We identified entities based on molecular delimitations and/or the checklist of European butterflies and objectively attributed occurrences to their most probable entity. We obtained a zoogeographic regionalisation based on the 69 endemics of the area. Using phylogenetic ANOVA we tested if endemics from different centres differ from each other and from nonendemics for key ecological traits and divergence time. Endemicity showed high incidence in the Alps and Southern Italy. The regionalisation separated the Alps from the Italian Peninsula and Sicily. The endemics of different centres showed a high turnover and differed in phylogenetic distances, phenology and distribution traits. Endemics are on average younger than nonendemics and the Peninsula-Sicily endemics also have lower variance in divergence than those from the Alps. The observed variation identifies Alpine endemics as paleoendemics, now occupying an ecological centre, and the Peninsula-Sicily ones as neoendemics, that diverged in the region since the Pleistocene. The results challenge the common view of the Alpine-Apennine area as a single “Italian refugium”

A comparison of sacral neuromodulation vs. transvaginal electrical stimulation for the treatment of refractory overactive bladder: The impact on quality of life, body image, sexual function, and emotional well-being

Overactive bladder syndrome (OAB) is defined by the presence of urinary urgency, with or without urge incontinence, usually accompanied by an increase in urinary frequency and nocturia in the absence of urinary tract infections (UTI) or other diseases. The overall prevalence of OAB symptoms in the female population is reported to be 16.6% and increases with advancing age and menopause. The aetiology of OAB is not fully understood and is likely to affect a heterogeneous population of patients due to changes to their central and peripheral nervous systems. Although OAB is frequently associated with female sexual dysfunction (FSD), its real impact on sexual function in women has been evaluated only in a few studies. The first line of treatment for OAB includes behavioural modification and physical therapy, either as monotherapies or in combination. Many patients who have not had success in managing their symptoms with more conservative therapies may decide to resort to third-line treatments for refractory OAB. These treatments include neuromodulation therapies, particularly transvaginal electrical stimulation (TES) and sacral neuromodulation (SN). The aim of this short commentary is to provide an overview of the effectiveness of these treatments and of their impact on quality of life, body image, sexual function, and emotional well-being

Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94

Foreground removal from CMB temperature maps using an MLP neural network

One of the main obstacles in extracting the Cosmic Microwave Background (CMB) signal from observations in the mm-submm range is the foreground contamination by emission from galactic components: mainly synchrotron, free-free and thermal dust emission. Due to the statistical nature of the intrinsic CMB signal it is essential to minimize the systematic errors in the CMB temperature determinations. Following the available knowledge of the spectral behavior of the galactic foregrounds simple, power law-like spectra have been assumed. The feasibility of using a simple neural network for extracting the CMB temperature signal from the combined CMB and foreground signals has been investigated. As a specific example, we have analysed simulated data, like that expected from the ESA Planck Surveyor mission. A simple multilayer perceptron neural network with 2 hidden layers can provide temperature estimates, over more than 80 percent of the sky, that are to a high degree uncorrelated with the foreground signals. A single network will be able to cover the dynamic range of the Planck noise level over the entire sky.Comment: Accepted for publication in Astrophysics and Space Scienc

The isolated Erebia pandrose Apennine population is genetically unique and endangered by climate change

Climate change is causing shifts in the distribution of many species and populations inhabiting mountain tops are particularly vulnerable to these threats because they are constrained in altitudinal shifts. Apennines are a relatively narrow and low mountain chain located in Southern Europe, which hosts many isolated populations of mountain species. The butterfly Erebia pandrose was recorded for the last time in the Apennines in 1977, on the top of a single massif (Monti della Laga). We confirmed the presence of a small, isolated population of E. pandrose in the Apennines, at a distance of more than 400 km to any other known populations. Then, we examined the cytochrome c oxidase subunit 1 mitochondrial DNA marker of this species across the Palaearctic area and estimated the potential decline over the Alps and the Apennines due to future climatic changes. The Apennine population represents an endemic lineage characterised by eight mutations over the 658 bp analysed (1.2%). In the Alps and Apennines, this species has shifted uphill more than 3 m per year since the end of the 19th century and more than 22 m per year since 1995. Species distribution models suggested that these mountain populations will experience a generalised loss of climatic suitability, which, according to our projections, could lead to the extinction of the Apennine population in a few decades. Erebia pandrose has the potential to become a flagship species for advertising the risk of losing unique fractions of genetic diversity for mountain species

Realistic Simulations of the Galactic Polarized Foreground: Consequences for 21-cm Reionization Detection Experiments

Experiments designed to measure the redshifted 21~cm line from the Epoch of Reionization (EoR) are challenged by strong astrophysical foreground contamination, ionospheric distortions, complex instrumental response and other different types of noise (e.g. radio frequency interference). The astrophysical foregrounds are dominated by diffuse synchrotron emission from our Galaxy. Here we present a simulation of the Galactic emission used as a foreground module for the LOFAR- EoR key science project end-to-end simulations. The simulation produces total and polarized intensity over $10^\circ \times 10^\circ$ maps of the Galactic synchrotron and free-free emission, including all observed characteristics of the emission: spatial fluctuations of amplitude and spectral index of the synchrotron emission, together with Faraday rotation effects. The importance of these simulations arise from the fact that the Galactic polarized emission could behave in a manner similar to the EoR signal along the frequency direction. As a consequence, an improper instrumental calibration will give rise to leakages of the polarized to the total signal and mask the desired EoR signal. In this paper we address this for the first time through realistic simulations.Comment: 14 pages, 8 figures, published in MNRA

Foreground simulations for the LOFAR - Epoch of Reionization Experiment

Future high redshift 21-cm experiments will suffer from a high degree of contamination, due both to astrophysical foregrounds and to non-astrophysical and instrumental effects. In order to reliably extract the cosmological signal from the observed data, it is essential to understand very well all data components and their influence on the extracted signal. Here we present simulated astrophysical foregrounds datacubes and discuss their possible statistical effects on the data. The foreground maps are produced assuming 5 deg x 5 deg windows that match those expected to be observed by the LOFAR Epoch-of-Reionization (EoR) key science project. We show that with the expected LOFAR-EoR sky and receiver noise levels, which amount to ~52 mK at 150 MHz after 300 hours of total observing time, a simple polynomial fit allows a statistical reconstruction of the signal. We also show that the polynomial fitting will work for maps with realistic yet idealised instrument response, i.e., a response that includes only a uniform uv coverage as a function of frequency and ignores many other uncertainties. Polarized galactic synchrotron maps that include internal polarization and a number of Faraday screens along the line of sight are also simulated. The importance of these stems from the fact that the LOFAR instrument, in common with all current interferometric EoR experiments has an instrumentally polarized response.Comment: 18 figures, 3 tables, accepted to be published in MNRA

Combining Mini-Mental State Examination and Montreal Cognitive Assessment for assessing the clinical efficacy of cholinesterase inhibitors in mild Alzheimer's disease: a pilot study

Current drugs for Alzheimer's Disease (AD), such as cholinesterase inhibitors (ChEIs), exert only symptomatic activity. Different psychometric tools are needed to assess cognitive and non-cognitive dimensions during pharmacological treatment. In this pilot study, we monitored 33 mild-AD patients treated with ChEIs. Specifically, we evaluated the effects of 6 months (Group 1 = 17 patients) and 9 months (Group 2 = 16 patients) of ChEIs administration on cognition with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Frontal Assessment Battery (FAB), while depressive symptoms were measured with the Hamilton Depression Rating Scale (HDRS). After 6 months (Group 1), a significant decrease in MoCA performance was detected. After 9 months (Group 2), a significant decrease in MMSE, MoCA, and FAB performance was observed. ChEIs did not modify depressive symptoms. Overall, our data suggest MoCA is a potentially useful tool for evaluating the effectiveness of ChEIs

Emerging toxicities in the treatment of non-small cell lung cancer : ocular disorders

The treatment of advanced disease (stage IIIb and IV) of non-small cell lung cancer (NSCLC) is based on systemic treatment with platinum-based chemotherapy or biological compounds depending on the disease molecular profile. In the last few years, intensive investigational efforts in anticancer therapy have led to the registration of new active chemotherapeutic agents, combination regimens, and biological drugs, expanding choices for customizing individual treatment. However, the introduction of new drugs in the clinical setting has led to several new toxicities, creating some difficulties in daily management. Among these, ocular toxicity is generally overlooked as more common toxicities such as myelosuppression, stomatitis, diarrhea, vomiting, "hand-foot syndrome", and neurological alterations attract greater attention. Ophthalmic complications from cytotoxic chemotherapeutics are rare, transient, and of mild/moderate intensity but irreversible acute disorders are possible. The best way to prevent potential irreversible visual complications is an awareness of the potential for ocular toxicity because dose reductions or early drug cessation can prevent serious ocular complications in the majority of cases. However, given the novelty of many therapeutic agents and the complexity of ocular pathology, oncologists may be unfamiliar with these adverse effects of anticancer therapy. Although toxicities from chemotherapy are generally intense but short lasting, toxicities related to targeted drugs are often milder but longer lasting and can persist throughout treatment. Here we review the principal clinical presentations of ocular toxicity arising from chemotherapy [1-3], target therapies [4], and newly developed drugs and provide some recommendations for monitoring and management of ocular toxicity