Numerical modeling as a tool for evaluating the renewability of geothermal resources: the case study of the Euganean Geothermal System (NE Italy).

Renewable natural resources are strategic for reducing greenhouse gas emissions and the human footprint. The renewability of these resources is a crucial aspect that should be evaluated in utilization of scenario planning. The renewability of geothermal resources is strictly related to the physical and geological processes that favor water circulation and heating. In the Veneto region (NE Italy), thermal waters of the Euganean Geothermal System are the most profitable regional geothermal resource, and its renewability assessment entails the evaluation of fluid and heat recharge, regional and local geological settings, and physical processes controlling system development. This renewability assessment is aimed at defining both the importance of such components and the resource amount that can be exploited without compromising its future preservation. In the second part of the twentieth century, the Euganean thermal resource was threatened by severe overexploitation that caused a sharp decrease in the potentiometric level of the thermal aquifers. Consequently, regulation for their exploitation is required. In this work, the renewability of the Euganean Geothermal System was assessed using the results from numerical simulations of fluid flow and heat transport. The simulations were based on a detailed hydrogeological reconstruction that reproduced major regional geological heterogeneities through a 3D unstructured mesh, while a heterogeneous permeability field was used to reproduce the local fracturing of the thermal aquifers. The model results highlight the role played by the resolved structural elements, in particular the subsurface high-angle faults of the exploitation field, and by the anomalous regional crustal heat flow affecting the central Veneto region.

Specific dermatoses of pregnancy other than pemphigoid gestationis.

Specific dermatoses of pregnancy are skin disorders that occur specifically during or immediately after pregnancy and cannot be found in non-pregnant patients. According to the current consensus, they include atopic eruption of pregnancy (AEP), polymorphic eruption of pregnancy (PEP), pemphigoid gestationis (PG), and intrahepatic cholestasis of pregnancy (ICP). The diagnosis of specific dermatoses of pregnancy can be challenging due to their variation in clinical presentation; moreover, the tests currently available do not always provide the clue for the diagnosis. However, some distinctive features may be helpful to differentiate between such entities. Accordingly, the knowledge of specific dermatoses of pregnancy and of their management is critical, since their early recognition may allow to provide care for the mother and prevent potential increased fetal risk. In fact, while AEP and PEP do not affect maternal and fetal prognosis, PG and, mainly, ICP are associated to maternal complications as well as the risk of fetal loss. In this paper, the epidemiology, pathogenesis, clinical features as well as management of AEP and PEP are reviewed in detail, while PG is described in another article of this issue. Moreover, the main features of ICP, which cannot be considered a primarily skin disease but may be managed first by dermatologists, are reported.

Geostatistics as a tool to improve the natural background level definition: An application in groundwater.

The Natural Background Level (NBL), suggested by UE BRIDGE project, is suited for spatially distributed datasets providing a regional value that could be higher than the Threshold Value (TV) set by every country. In hydro-geochemically dis-homogeneous areas, the use of a unique regional NBL, higher than TV, could arise problems to distinguish between natural occurrences and anthropogenic contaminant sources. Hence, the goal of this study is to improve the NBL definition employing a geostatistical approach, which reconstructs the contaminant spatial structure accounting geochemical and hydrogeological relationships. This integrated mapping is fundamental to evaluate the contaminant's distribution impact on the NBL, giving indications to improve it. We decided to test this method on the Drainage Basin of Venice Lagoon (DBVL, NE Italy), where the existing NBL is seven times higher than the TV. This area is notoriously affected by naturally occurring arsenic contamination. An available geochemical dataset collected by 50 piezometers was used to reconstruct the spatial distribution of arsenic in the densely populated area of the DBVL. A cokriging approach was applied exploiting the geochemical relationships among As, Fe and NH4+. The obtained spatial predictions of arsenic concentrations were divided into three different zones: i) areas with an As concentration lower than the TV, ii) areas with an As concentration between the TV and the median of the values higher than the TV, and iii) areas with an As concentration higher than the median. Following the BRIDGE suggestions, where enough samples were available, the 90th percentile for each zone was calculated to obtain a local NBL (LNBL). Differently from the original NBL, this local value gives more detailed water quality information accounting the hydrogeological and geochemical setting, and contaminant spatial variation. Hence, the LNBL could give more indications about the distinction between natural occurrence and anthropogenic contamination.

Tuscan consensus on the diagnosis, treatment and follow-up of moderate-to-severe psoriasis.

BACKGROUND: Psoriasis is traditionally defined as an inflammatory chronic-relapsing disease of the skin. As widely demonstrated, this disease is also associated with multiple comorbidities: arthropathy, inflammatory bowel disease, metabolic, cardiovascular, ocular and psychological disorders. The disease also has a significant impact on patients' quality of life, whose work ability decreases considerably with clear consequences for the social costs. Therefore, if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer from psoriasis, it is of paramount importance focusing the attention on a rational model of clinical and therapeutic management of the disease. All the leading experts in Tuscany have come together with the aim of defining unanimously accepted regional guidelines for the diagnosis, treatment, follow-up and management of psoriasis, and of providing practical guidance/protocol on diagnosis, treatment, follow-up and management of special cases of moderate-to-severe plaque psoriasis. METHODS: In a working group formed ad hoc, the main topics have been discussed and approved by plenary vote. RESULTS: Diagnosis must include a proper general health condition overview, a careful evaluation of skin and joints, the assessment and management of other comorbidities and the definition of disease severity. With regards to the therapy the best time to start a systemic treatment, the therapeutic goal, the most appropriate drug and blood tests to be performed in case of moderate severe-psoriasis have been taken into account. During follow-up, proper monitoring of systemic therapy and its management in the long term has also been suggested. Eventually, the experts have addressed the problem of how to manage the disease in special conditions, such as during surgery, pregnancy, in children and in case of infections (HBV, HCV, HIV). CONCLUSIONS: The main aim of this Consensus was to find agreement on the criteria for diagnosis, treatment and follow-up of psoriasis, shared by all the Dermatologic Therapy Units of Tuscany. A need to create an easier way for the patient to access specialized dermatology outpatient services, and to reduce the waiting list and costs related to the management of psoriasis has been stressed. Most importantly, during the Consensus all of the participants agreed on the central role of the patient, and on the need of a multidisciplinary management of the disease which requires communication among specialists and regional centers in order to build on existing experience.

Persistent Neutrophil to Lymphocyte Ratio >3 during Treatment with Enzalutamide and Clinical Outcome in Patients with Castration-Resistant Prostate Cancer.

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ≤3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8-90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7-4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5-9.7) in those with NLR ≤3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5-14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2-20.9) in those with baseline NLR ≤3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07-1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10-1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients.

Association Between Early PSA Increase and Clinical Outcome in Patients Treated with Enzalutamide for Metastatic Castration Resistant Prostate Cancer.

OBJECTIVE: Prostate-specific antigen (PSA) decline by 50 % from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the association between PSA changes at 4 weeks and clinical outcome. PATIENTS AND METHODS: Eligible patients had PSA levels assessed at baseline, and monthly during enzalutamide treatment. Early PSA increase was defined as an increased PSA level at 4 weeks ≥20 % (PSA + 20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥30 % (PSA30w4) and ≥50 % (PSA50w4) from baseline. Progression-free survival (PFS), overall survival (OS) and their 95 % confidence intervals (CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. The impact of early PSA increase and decline on PFS and OS was evaluated by Cox regression analyses. RESULTS: We assessed 193 patients with median age of 73 years (range 43-91 years). The median follow-up was 11.7 months (range 0.5-27.4 months). PSA + 20w4 predicted both PFS and OS [HR 6.50 (95 % CI 2.63-16.07; p < 0.0001) and HR 10.54 (95 % CI 4.02-27.64; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95 % CI 0.21-0.67; p = 0.0009) and HR 0.34 (95 % CI 0.19-0.60; p = 0.0003), respectively]. CONCLUSIONS: An early PSA increase, defined as a PSA level at 4 weeks ≥20 % (PSA + 20w4), could be useful to quickly identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA + 20W4 as an early biomarker of primary resistance to enzalutamide.

Dental Age Estimation Helps Create a New Identity.

Age estimation involves the reconstruction of age by biological parameters such as skeletal and dental development in minors, or reduction of pulp chamber in adults, to gain indications concerning the chronological age of the person. In most cases, it is needed in forensic scenarios to verify if the supposed age of an individual is correct; in exceptional cases, age estimation is instead required by judicial authorities to create a new identity usually in persons who do not remember who they are.This article aims at reporting the case of J. who was found in 2005 with signs of amnesia because he did not remember his name and age. After several unsuccessful attempts at identifying him, the judicial authority decided to assign a new identity, which was to be constructed according to the real biological data of the individual. The help of a forensic pathologist and a forensic odontologist was then requested, and age estimation was reached by applying methods for adults based on the physiological reduction of pulp chamber. Dental age estimation yielded a final result of approximately 31 years, which was the new age assigned to the person.This article shows a peculiar application of dental age estimation, which can be used not only to ascertain or deny supposed age, but is sometimes needed to create a new identity.

Regulatory T cells as well as IL-10 are reduced in the skin of patients with dermatitis herpetiformis.

BACKGROUND: Dermatitis herpetiformis (DH) and celiac disease (CD) are considered as autoimmune diseases that share a defined trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not fully understood and no data are available about the immune regulation in such a disease. OBJECTIVE: The aim of this study was to assess if alterations in the pattern of the immune response and, in particular, impairments of regulatory T (Tregs) cells may contribute to the phenotypic differences between DH and CD. METHODS: We investigated the presence of Tregs cell markers, in the skin, the duodenum and the blood of patients with DH by immunohistochemistry, confocal microscopy and flow cytometry. As controls, we included patients with bullous pemphigoid, patients with CD without skin lesions, as well as healthy subjects (HS). RESULTS: In the skin of DH patient, we found a significantly lower proportion of FOXP3(+) Tregs and IL-10(+) cells than in HS (p < 0.001 for both cell populations). In duodenal samples, no differences where found in the proportion of Tregs between patients with DH and patients with CD without skin manifestations. Finally, the frequency of CD25(bright)FOXP3(+) cells within the CD4(+) subset was significantly reduced in CD patients either with or without DH with respect to HS (p = 0.029 and p = 0.017, respectively). CONCLUSIONS: Our findings suggested that a reduction of Tregs may play a major role in the skin, leading to a defective suppressive function and thus to the development of the lesions. By contrast, no differences could be detected about Tregs between patients with DH and patients with CD in the duodenum, suggesting that the mechanisms of the intestinal damage are similar in both diseases.

PSA flare with abiraterone in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: The aim of this study was to assess early serum prostate-specific antigen (PSA) changes in patients treated with abiraterone and to correlate those changes with clinical outcome. PATIENTS AND METHODS: We retrospectively evaluated 103 patients with castrate-resistant prostate cancer (CRPC) treated with compassionate use of abiraterone in Romagna, Italy. In these patients, serum PSA levels were monitored every 4 weeks, and a time course of serum PSA levels was obtained. The PSA flare phenomenon was evaluated. The log-rank test was applied to compare survival between groups of patients according to early PSA level changes. RESULTS: Of 103 patients, 43 (41.7%) had an immediate PSA response, whereas 9 (8.7%) had an initial PSA flare. Of the 9 patients with PSA flare, 5 attained a subsequent PSA response. The temporary PSA flare exceeded baseline values by a median of 19.7% (range, 5%-62.9%). The median PFS of the 9 patients in the PSA-flare group was higher compared with patients without the PSA flare (10.5 vs. 6.4 months; P = .0999) but was similar to the subgroup of patients with immediate PSA response (10.5 vs. 10.7 months; P = .7019). In the multivariate analysis, only the PSA response remained as a predictor of progression-free survival (PFS) (P < .0001) and overall survival (OS) (P = .0003), respectively. CONCLUSION: PSA flare occurs not infrequently in patients with CRPC who respond to abiraterone. Patients should be informed of this possible PSA flare phenomenon.

Metabolic syndrome prevalence in psoriasis: a cross-sectional study in the Italian population.

BACKGROUND: The pathogenesis of psoriasis is complex, with a significant role suggested for pro-inflammatory mediators. There is strong evidence of an association between psoriasis and the metabolic syndrome (MetS), a cluster of cardiovascular risk factors, which impose a substantial disease burden. OBJECTIVE: This study aimed to evaluate the prevalence of MetS and to examine the implications of disease severity, type 2 diabetes mellitus, and cardiovascular disease in a large cohort of Italian psoriatic patients representative of the whole population. METHODS: This was a cross-sectional study involving 13 dermatological clinics in Italy. The primary study endpoint was a comparison of the prevalence of MetS between psoriatic patients and a non-psoriatic control group; secondary endpoints included the influence of psoriasis severity on the prevalence of MetS, and the relative prevalence and risk of type 2 diabetes mellitus and cardiovascular disorders. RESULTS: A total of 720 patients were enrolled (n = 360 per group). The prevalence of MetS was 26.84% in the psoriatic population and 15.16% in the control population (p = 0.0001; adjusted odds ratio 1.96). MetS was associated with a greater degree of psoriasis severity, and the prevalence and risk of diabetes tended to be higher in psoriatic patients than in the control group. CONCLUSION: In the Italian population, the prevalence of MetS and associated comorbidities is elevated in patients with psoriasis compared with non-psoriatic subjects, as has been demonstrated in other countries. Our findings reinforce the importance of considering the implications of metabolic comorbidities in treating patients with psoriasis.

Linear immunoglobulin a bullous dermatosis: need for an agreement on diagnostic criteria.

Linear immunoglobulin A bullous dermatosis (LABD) is a rare, heterogeneous, autoimmune blistering disorder. Although the main characteristics of the disease seem to be well identified, international accepted diagnostic criteria are lacking. Several authors suggested their own criteria, but they are often not complete or even in contrast with clinical and immunopathological findings from the literature, while others are too selective. In this review, the current views and the problems with the definition of reliable diagnostic criteria for LABD will be discussed.

Assessing transmissivity from specific capacity in an alluvial aquifer in the middle Venetian plain (NE Italy).

Defining aquifer permeability distribution accurately over large areas is often debated in hydrogeology. The operational efforts to calculate hydraulic conductivity with classical aquifer tests are significant; however, accurate knowledge of permeability areal distribution is fundamental both from a hydrogeological and a modeling standpoint. This paper presents an empirical relationship between the transmissivity (T) and the specific capacity (SC) values obtained from experimental aquifer and well tests. All experimental values were obtained from 50 mm wells in middle Venetian plain artesian gravel aquifers. Many other authors have presented empirical relationships between T and SC, but most are related to fissured/karst aquifers, and only a few concern alluvial porous aquifers. Analysis of the T vs. SC relationship standardized residuals shows that a linear relationship produces statistically significant normal residuals compared with an exponential relationship.

Neo-epitope tissue transglutaminase autoantibodies as a biomarker of the gluten sensitive skin disease--dermatitis herpetiformis.

BACKGROUND: The deamidated gliadin peptides (DGP) cross linked to human tissue transglutaminase (tTg) comprises a novel neo-epitope structure (Neo-tTg) for serological screening of celiac disease (CD). Our aim is to verify anti-Neo-tTg IgA and IgG in adults with dermatitis herpetiformis (DH). METHODS: Multi-centric retrospective evaluation of the IgA/G autoantibodies in sera of DH patients on a regular diet (n=40) and a gluten restricted diet (GRD, n=53) and control adults with autoimmune skin diseases (n=107) by ELISA. RESULTS: The sensitivities of Celicheck Neo IgA/G (76%, 95% CI 67-84%) and the Neo tTg-A (85%, 95% CI 70-97%) ELISA were significantly greater than that of tTg-A (56%, 95% CI 46-67%), eTg-A (62%, 95% CI 52-72%), DGP-A (55%, 95% CI 55-65%), DGP-G (61%, 95% CI 51-71%), Glia-A (55%, 95% CI 45-65%) and Glia-G (56%, 95% CI 46-66%) ELISA. The specificities of all 8 ELISA were in the range of 90-100%. The area under the curve (AUC) of receiver operator characteristic curve (ROC) for the two Neo-tTg ELISA (0.863 and 0.949) were higher than the AUCs for ROCs of tTg, DGP and eTG ELISA (range between 0.657 and 0.783). The autoantibody levels of DH patients on a normal diet were significantly higher than those on GRD in the Celicheck Neo IgA/IgG, NeotTg-A; tTg-A and the eTg-A; ELISA (p<0.01) and of no significance in the DGP and Gliadin ELISA. CONCLUSION: Neo-epitope IgA autoantibodies represent a new and sensitive serological marker of DH.

Hailey-Hailey disease treated with methotrexate.

BACKGROUND: Hailey-Hailey disease (HHD) is a chronic, recurrent blistering disorder characterized clinically by erosions occurring primarily in intertriginous regions and histologically by suprabasal acantholysis. MAIN OBSERVATIONS: We report a long standing case of HHD initially unresponsive to cyclosporin, multiple topical and systemic steroids. Good response was achieved with methotrexate 7,5 mg weekly for 16 week, intramuscularly, and topical steroids as needed. CONCLUSION: In conclusion, we suggest that methotrexate could be considered a therapeutic option for the treatment of HHD and in particular as a maintaining therapy to control the disease flares.

Dermatitis herpetiformis: from the genetics to the development of skin lesions.

Dermatitis herpetiformis (DH) is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD). Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions.