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The link between winter (December-January-February) precipitation events at 15 Mediterranean coastal locations and synoptic features (cyclones and Northern Hemisphere teleconnection patterns) is analyzed. A list of precipitation events has been produced; q percentile thresholds (Thq) and corresponding frequency Nq (for q equal to 25, 50, 90 and 98) have been considered. A negative trend has been detected in total precipitation and N50 at many locations, while no significant trend in N25, N90 and N98 has been found. The negative phase of the North Atlantic Oscillation (NAO) and the East Atlantic/West Russia pattern (EAWR) compete for exerting the largest influence on the frequency of the 25th, 50th and 90th percentiles, with EAWR and NAO exerting their largest influence in the central and western Mediterranean areas, respectively. All percentiles show a similar behavior except for the 98th percentile, which shows no convincing link to any teleconnection pattern. The cyclone tracks that are associated with precipitation events have been selected using the ERA-40 reanalysis data, and a strong link between intense precipitation and cyclones is shown for all stations. In general, the probability of detecting a cyclone within a distance of 20° from each station increases with the intensity of the precipitation event and decreases with the duration of a dry period. The origin and track of cyclones producing intense precipitation differ among different areas. When precipitation occurs in the northwestern Mediterranean, cyclones are generally either of Atlantic origin or secondary cyclones associated with the passage of major cyclones north of the Mediterranean Basin, while they are mostly generated inside the region itself for events at the eastern Mediterranean coast. An important fraction of intense events in the southern areas is produced by cyclones that are generated over northern Africa. The analysis of sea level pressure and geopotential height at 500 hPa highlights the important role of cyclone depth, circulation strength, surrounding synoptic condition, and of slow speed of the cyclone center for producing intense precipitation events.

We investigate the response of winter precipitation and storm activity in the North Atlantic–European–Mediterranean region (NAEM) to the Indian Ocean Dipole (IOD) from 1979 to 2024. We observe a positive NAO‐like pattern over NAEM, which appears in December and shifts eastward through February. IOD further modulates precipitation by inducing changes in total precipitation, event frequency, and wet spell duration. The strength of the observed teleconnection is primarily significant in December. Additionally, we observe a reduction in cyclone activity in December over the East Atlantic and Western Mediterranean. These changes in cyclone track density are primarily driven by variations in the Eady Growth Rate, which are linked to enhanced vertical wind shear associated with a strengthened meridional temperature gradient over the NAEM. The results underscore a significant remote impact of the IOD on early winter hydro‐climate variability over the NAEM region, offering a potential value for improving sub‐seasonal to seasonal prediction.

Sjögren’s syndrome (SS) or sicca syndrome was described by Swedish ophthalmologist Sjögren in the year 1933 for the first time. The etiology of the SS is multifunctional and includes a combination of genetic predisposition and environmental as well as epigenetic factors. It is an autoimmune disease characterized by features of systemic autoimmunity, dysfunction, and inflammation in the exocrine glands (mainly salivary and lacrimal glands) and lymphocytic infiltration of exocrine glands. In fact, the involvement of lacrimal and salivary glands results in the typical features of dry eye and salivary dysfunction (xerostomia). Only in one-third of the patients also present systemic extraglandular manifestations. T cells were originally considered to play the initiating role in the autoimmune process, while B cells were restricted to autoantibody production. In recent years, it is understood that the roles of B cells are multiple. Moreover, autoantibodies and blood B cell analysis are major contributors to a clinical diagnosis of Sjögren’s syndrome. Recently, there has been rising interest in microRNA implication in autoimmunity. Unfortunately, to date, there are only a few studies that have investigated their participation in SS etiopathogenesis. The purpose of this work is to gather the data present in the literature to clarify this complex topic.

Background The diffuse distribution of nicotinic cholinergic receptors (nAChRs) in both brain and peripheral immune cells points out their involvement in several pathological conditions. Indeed, the deregulated function of the nAChR was previously correlated with cognitive decline and neuropsychiatric symptoms in Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB). The evaluation in peripheral immune cells of nAChR subtypes, which could reflect their expression in brain regions, is a prominent investigation area. Objectives This study aims to evaluate the expression levels of both the nAChR subunits and the main known inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with DLB and AD to better characterize their involvement in these two diseases. Results Higher gene expression levels of TNFα, IL6 and IL1β were observed in DLB and AD patients in comparison with healthy controls (HC). In our cohort, a reduction of nAChRα4, nAChRβ2 and nAChRβ4 was detected in both DLB and AD with respect to HC. Considering nAChR gene expressions in DLB and AD, significant differences were observed for nAChRα3, nAChRα4, nAChRβ2 and nAChRβ4 between the two groups. Moreover, the acetylcholine esterase (AChE) gene expression was significantly higher in DLB than in AD. Correlation analysis points out the relation between different nAChR subtype expressions in DLB (nAChRβ2 vs nAChRα3; nAChRα4 vs nAChRα3) and AD (nAChRα4 vs nAChRα3; nAChRα4 vs nAChRβ4; nAChRα7 vs nAChRα3; nAChRα7 vs nAChRα4). Conclusions Different gene expressions of both pro-inflammatory cytokines and nAChR subtypes may represent a peripheral link between inflammation and neurodegeneration. Inflammatory cytokines and different nAChRs should be valid and accurate peripheral markers for the clinical diagnosis of DLB and AD. However, although nAChRs show a great biological role in the regulation of inflammation, no significant correlation was detected between nAChR subtypes and the examined cytokines in our cohort of patients.

Purpose There is no agreement on the most appropriate post-operative pathway for the management of positive margins after laser cordectomy for early stage glottic tumours (T1-2N0M0). This literature review and meta-analysis aim to evaluate the post-operative treatment with the best oncological results among follow-up, radiotherapy (RT) and surgical second look. The parameters utilized were incidence of recurrence, overall (OS), disease-specific (DSS) and disease-free (DFS) survival and larynx preservation (LP). Methods The articles were found through a string typed into PubMed from 2007 to 2022. The studies with detailed oncological results were selected according to inclusion criteria, and then the meta-analysis was carried out. Results Sixteen studies met the inclusion criteria for 2808 patients. The positive margin was found in 748 patients (26.6%), of which 416 were referred to follow-up, 89 to RT and 242 to a surgical second look. A false positive margin was found in 58/104 patients (56%). The recurrence rate in patients with positive margins was significantly higher ( p  = 0.003). In OS, DSS, DFS and LP, the odds ratio (OR) value was always greater than 1, assessing the role of the positive margin as a risk factor. Conclusions Prospective studies will be necessary to establish the role of positive margin as a prognostic factor. A surgical second look in case of positive margin seems to be the best option for the patient in terms of lower risk of recurrence and better oncological results. Better collaboration between surgeon and pathologist would be desirable to limit the real and false positive margins.

An adaptation of the oscars algorithm for bound constrained global optimization is presented, and numerically tested. The algorithm is a stochastic direct search method, and has low overheads which are constant per sample point. Some sample points are drawn randomly in the feasible region from time to time, ensuring global convergence almost surely under mild conditions. Additional sample points are preferentially placed near previous good sample points to improve the rate of convergence. Connections with partitioning strategies are explored for oscars and the new method, showing these methods have a reduced risk of sample point redundancy. Numerical testing shows that the method is viable in practice, and is substantially faster than oscars in 4 or more dimensions. Comparison with other methods shows good performance in moderately high dimensions. A power law test for identifying and avoiding proper local minima is presented and shown to give modest improvement.

We investigated the effects of variations in the 4 primary mid-latitude large-scale atmospheric circulation patterns on nutrients potentially limiting phytoplankton growth in the Mediterranean Sea (nitrate and phosphate), with a focus on the key deep convective areas of the basin (Gulf of Lions, Southern Adriatic Sea, Southern Aegean Sea and Rhodes Gyre). Monthly indices of these 4 modes of variability, together with a high-resolution hindcast of the Mediterranean Sea physics and biogeochemistry covering the period 1961–1999, were used to determine the physical mechanisms explaining the influence of these patterns on nutrient distribution and variability. We found a decrease in the concentration of phosphate and nitrate for each unit of increase in the index values of the East Atlantic and East Atlantic/West Russian variability modes in the area of the Gulf of Lions, while a signal of the opposite sign was associated with the North Atlantic Oscillation in the Aegean Sea and Rhodes Gyre. In both cases, the variability observed was related to a significant variation in the mixed layer depth driven by heat losses and wind stress over the areas. The East Atlantic pattern played a major role in driving the long-term dynamics of both phosphate and nitrate availability in the Gulf of Lions, with a particularly pronounced effect in December and January. For both the Aegean Sea and Rhodes Gyre, the most prominent correlations were found between the North Atlantic Oscillation and phosphate, with a highly consistent behavior in the 2 areas associated with common physical forcing and exchange of properties among them.

We describe a new, state‐of‐the‐art, Earth System Regional Climate Model (RegCM‐ES), which includes the coupling between the atmosphere, ocean, and land surface, as well as a hydrological and ocean biogeochemistry model, with the capability of using a variety of physical parameterizations. The regional coupled model has been implemented and tested over some of the COordinated Regional climate Downscaling Experiment (CORDEX) domains and more regional settings featuring climatically important coupled phenomena. Regional coupled ocean‐atmosphere models can be especially useful tools to provide information on the mechanisms of air‐sea interactions and feedbacks occurring at fine spatial and temporal scales. RegCM‐ES shows a good representation of precipitation and SST fields over the domains tested, as well as realistic simulations of coupled air‐sea processes and interactions. The RegCM‐ES model, which can be easily implemented over any regional domain of interest, is open source, making it suitable for usage by the broad scientific community. Plain Language Summary The increasing availability of observational data sets of high temporal and spatial resolution is providing a more complete view of the ocean and atmosphere, revealing strong air‐sea coupling processes. In order to obtain an accurate representation and better understanding of the climate system, its variability, and possible future change, the inclusion of all mechanisms of interaction among the different climate components becomes ever more desirable. Regional coupled ocean‐atmosphere models can be especially useful tools to provide information on the mechanisms of air‐sea interactions and feedback occurring at regional fine spatial and temporal scales. Here we present a new, state‐of‐the‐art, Earth System Regional Climate Model (RegCM‐ES). Key Points A new Regional Earth System Model (RegCM‐ES) successfully simulates climate features in regions where coupled air‐sea processes are important RegCM‐ES shows reduction of precipitation biases and good performance simulating the effects of air‐sea interactions over frontal regions RegCM‐ES is an open source community model, making it suitable for use by a large scientific community on any regional domain of interest

The region of Apulia, which is located in the south-east tip of the Italian Peninsula, has a typical Mediterranean climate with mild winters and hot-dry summers. Agriculture, an important sector of its economy, is potentially threatened by future climate change. This study describes the evolution of seasonal temperature and precipitation from the recent past to the next decades and estimates future potential impacts of climate change on three main agricultural products: wine, wheat and olives. Analysis is based on instrumental data, on an ensemble of climate projections and on a linear regression model linking these three agricultural products to seasonal values of temperature and precipitation. In Apulia, precipitation and temperature time series show trends toward warmer and marginally drier conditions during the whole analyzed (1951–2005) period: 0.18 °C/decade in mean annual minimum temperature and −14.9 mm/decade in the annual total precipitation. Temperature trends have been progressively increasing and rates of change have become noticeably more intense during the last 25 years of the twentieth century. Model simulations are consistent with observed trends for the period 1951–2000 and show a large acceleration of the warming rate in the period 2001–2050 with respect to the period 1951–2000. Further, in the period 2001–2050, simulations show a decrease in precipitation, which was not present in the previous 50 years. Wine production, wheat and olive harvest records show large inter-annual variability with statistically significant links to seasonal temperature and precipitation, whose strength, however, strongly depends on the considered variables. Linear regression analysis shows that seasonal temperature and precipitation variability explains a small, but not negligible, fraction of the inter-annual variability of these crops (40, 18, 9 % for wine, olives and wheat, respectively). Results (which consider no adaptation of crops and no fertilization effect of CO₂) suggest that evolution of these seasonal climate variables in the first half of the twenty-first century could decrease all considered variables. The most affected is wine production (−20 ÷ −26 %). The effect is relevant also on harvested olives (−8 ÷ −19 %) and negligible on harvested wheat (−4 ÷ −1 %).

An 18-month-old infant presented to the emergency department following a fall from a couch onto a three-pin electrical plug that embedded in the right parietal area.