Spatial analysis of mean temperature trends in Spain over the period 1961–2006

The spatial distribution of recent mean temperature trends over Spain during the period 1961–2006 at monthly, seasonal and annual time scale is carried out in this study by applying various statistical tools to data from 473 weather stations. The magnitude of trends was derived from the slopes of the linear trends using ordinary least-square fitting. The non-parametric Mann–Kendall test was used to determine the statistical significance of trends. Maps of surface temperature trends were generated by applying a geostatistical interpolation technique to visualize the detected tendencies. This study reveals that temperature has generally increased during all months and seasons of the year over the last four decades. More than 60% of whole Spain has evidenced significant positive trends in March, June, August, spring and summer. This percentage diminishes around 40% in April, May and December. Annual temperature has significantly risen in 100% of Spain of around 0.1–0.2 °C/decade according to the Fourth Assessment Report of the IPCC

6 Aprile 2009. Il sisma, le rotture, le ricomposizioni.

Il lavoro di ricerca qui presentato prende le mosse dal terremoto che il 6 aprile 2009 ha colpito la città dell’Aquila in Abruzzo (Italia) e propone una lettura di alcune dinamiche sociali e spaziali che si sono sviluppate durante l’intero processo tellurico. All’Aquila si è di fronte ad una città distrutta che diventa palcoscenico di rappresentazioni di svariate dinamiche pertanto si tenterà da un lato di osservare come e in che misura una città, ed in particolare quella dell’Aquila, si trasforma sotto i suoi aspetti sociali, spaziali e culturali a seguito di un evento traumatico come quello del terremoto; dall’altro si ricostruirà il punto di vista, le percezioni, le rappresentazioni soggettive della catastrofe e il rapporto con gli spazi degli attori implicati nell’evento distruttivo. L’approccio di cui la ricerca si avvale è prevalentemente qualitativo: sono state svolte interviste in profondità ad abitanti e semi-strutturate ad expertises

Nomogram to predict the outcomes of patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors

Neoplasias gastrointestinales; InmunoterapiaNeoplàsies gastrointestinals; ImmunoteràpiaGastrointestinal neoplasms; ImmunotherapyBackground The efficacy of immune checkpoint inhibitors (ICIs) in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC) is unprecedented. A relevant proportion of subjects achieving durable disease control may be considered potentially ‘cured’, as opposed to patients experiencing primary ICI refractoriness or short-term clinical benefit. We developed and externally validated a nomogram to estimate the progression-free survival (PFS) and the time-independent event-free probability (EFP) in patients with MSI-high mCRC receiving ICIs. Methods The PFS and EFP were estimated using a cure model fitted on a developing set of 163 patients and validated on a set of 146 patients with MSI-high mCRC receiving anti-programmed death (ligand)1 (PD-(L)1) ± anticytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. A total of 23 putative prognostic factors were chosen and then selected using a random survival forest (RSF). The model performance in estimating PFS probability was evaluated by assessing calibration (internally—developing set and externally—validating set) and quantifying the discriminative ability (Harrell C index). Results RFS selected five variables: ICI type (anti-PD-(L)1 monotherapy vs anti-CTLA-4 combo), ECOG PS (0 vs >0), neutrophil-to-lymphocyte ratio (≤3 vs >3), platelet count, and prior treatment lines. As both in the developing and validation series most PFS events occurred within 12 months, this was chosen as cut-point for PFS prediction. The combination of the selected variables allowed estimation of the 12-month PFS (focused on patients with low chance of being cured) and the EFP (focused on patients likely to be event-free at a certain point of their follow-up). ICI type was significantly associated with disease control, as patients receiving the anti-CTLA-4-combination experienced the best outcomes. The calibration of PFS predictions was good both in the developing and validating sets. The median value of the EFP (46%) allowed segregation of two prognostic groups in both the developing (PFS HR=3.73, 95% CI 2.25 to 6.18; p<0.0001) and validating (PFS HR=1.86, 95% CI 1.07 to 3.23; p=0.0269) sets. Conclusions A nomogram based on five easily assessable variables including ICI treatment was built to estimate the outcomes of patients with MSI-high mCRC, with the potential to assist clinicians in their clinical practice. The web-based system ‘MSI mCRC Cure’ was released.The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors

My heart sings to me: song as the memory of language in the Arbëresh community of Chieuti

For the people of Chieuti who grew up speaking the Albanian dialect that the inhabitants of their Arbëresh town in the Italian province of Puglia have spoken for more than five centuries, the rapid decline of their mother tongue is a loss that is sorely felt. Musicians and cultural activists labor to negotiate new strategies for maintaining connections to their unique heritage and impart their traditions to young people who are raised speaking Italian in an increasingly interconnected world. As they perform, they are able to act out collective narratives of longing and belonging, history, nostalgia, and sense of place. Using the traditional song Rine Rine as a point of departure, this thesis examines how songs transmit linguistic and cultural markers of Arbëresh identity and serve to illuminate Chieuti's position as a community poised in the moment of language shift

Differences in the kinetic of the first meiotic division and in active mitochondrial distribution between prepubertal and adult oocytes mirror differences in their developmental competence in a sheep model

Our aim is to verify if oocyte developmental potential is related to the timing of meiotic progression and to mitochondrial distribution and activity using prepubertal and adult oocytes as models of low and high developmental capacity respectively. Prepubertal and adult oocytes were incorporated in an in vitro maturation system to determine meiotic and developmental competence and to assess at different time points kinetic of meiotic maturation, 2D protein electrophoresis patterns, ATP content and mitochondria distribution. Maturation and fertilization rates did not differ between prepubertal and adult oocytes (95.1% vs 96.7% and 66.73% vs 70.62% respectively for prepubertal and adult oocytes). Compared to adults, prepubertal oocytes showed higher parthenogenesis (17.38% vs 2.08% respectively in prepubertals and adults; P&#60;0.01) and polispermy (14.30% vs 2.21% respectively in prepubertals and adults; P&#60;0.01), lower cleavage rates (60.00% vs 67.08% respectively in prepubertals and adults; P&#60;0.05) and blastocyst output (11.94% vs 34.% respectively in prepubertals and adults; P&#60;0.01). Prepubertal oocytes reached MI stage 1 hr later than adults and this delay grows as the first meiotic division proceeds. Simultaneously, the protein pattern was altered since in prepubertal oocytes it fluctuates, dropping and rising to levels similar to adults only at 24 hrs. In prepubertal oocytes ATP rise is delayed and did not reach levels comparable to adult ones. CLSM observations revealed that at MII, in the majority of prepubertal oocytes, the active mitochondria are homogenously distributed, while in adults they are aggregated in big clusters. Our work demonstrates that mitochondria and their functional aggregation during maturation play an active role to provide energy in terms of ATP. The oocyte ATP content determines the timing of the meiotic cycle and the acquisition of developmental competence. Taken together our data suggest that oocytes with low developmental competence have a slowed down energetic metabolism which delays later development

Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cells by a novel NF-κB inhibitor

IT-901 is a novel and selective NF-κB inhibitor with promising activity in pre-clinical models. Here we show that treatment of chronic lymphocytic leukemia cells (CLL) with IT-901 effectively interrupts NF-κB transcriptional activity. CLL cells exposed to the drug display elevated mitochondrial reactive oxygen species, which damage mitochondria, limit oxidative phosphorylation and ATP production, and activate intrinsic apoptosis. Inhibition of NF-κB signaling in stromal and myeloid cells, both tumor-supportive elements, fails to induce apoptosis, but impairs NF-κB-driven expression of molecules involved in cell-cell contacts and immune responses, essential elements in creating a pro-leukemic niche. The consequence is that accessory cells do not protect CLL cells from IT-901-induced apoptosis. In this context, IT-901 shows synergistic activity with ibrutinib, arguing in favor of combination strategies. IT-901 is also effective in primary cells from patients with Richter syndrome (RS). Its anti-tumor properties are confirmed in xenograft models of CLL and in RS patient-derived xenografts, with documented NF-κB inhibition and significant reduction of tumor burden. Together, these results provide pre-clinical proof of principle for IT-901 as a potential new drug in CLL and RS

New investigations on the 32S(3He,d)33Cl reaction at 9.6 MeV bombarding energy

The 32S(3He,d)33Cl one-proton transfer reaction is a powerful tool to investigate the spectroscopy of low-lying states in the proton-rich 33Cl nucleus. However, the extraction of firm differential cross-section data at various angles to benchmark and constrain theoretical models is made challenging by the presence of competitive reactions on target contaminants. In this paper we report on arecent measurement using a new generation hodoscope of silicon detectors, capable to detect and identify emitted deuterons down to energies of the order of 2 MeV. The high angular segmentation of our hodoscope combined with a suitable target to control possible contaminants, allowed to unambiguously disentangle the contribution of various states in 33Cl, in particular the 2.352 MeV state lying just few tens of keV above the proton separation energy