Uncertainties in the adaptation of alpine pastures to climate change based on remote sensing products and modelling.

Over the last century, the management of pastoral systems has undergone major changes to meet the livelihood needs of alpine communities. Faced with the changes induced by recent global warming, the ecological status of many pastoral systems has seriously deteriorated in the western alpine region. We assessed changes in pasture dynamics by integrating information from remote-sensing products and two process-based models, i.e. the grassland-specific, biogeochemical growth model PaSim and the generic crop-growth model DayCent. Meteorological observations and satellite-derived Normalised Difference Vegetation Index (NDVI) trajectories of three pasture macro-types (high, medium and low productivity classes) in two study areas - Parc National des Écrins (PNE) in France and Parco Nazionale Gran Paradiso (PNGP) in Italy - were used as a basis for the model calibration work. The performance of the models was satisfactory in reproducing pasture production dynamics (R2 = 0.52 to 0.83). Projected changes in alpine pastures due to climate-change impacts and adaptation strategies indicate that: i) the length of the growing season is expected to increase between 15 and 40 days, resulting in changes in the timing and amount of biomass production, ii) summer water stress could limit pasture productivity; iii) earlier onset of grazing could enhance pasture productivity; iv) higher livestock densities could increase the rate of biomass regrowth, but major uncertainties in modelling processes need to be considered; and v) the carbon sequestration potential of pastures could decrease under limited water availability and warming.

Geographic tongue clinical response in moderate-to-severe psoriatic patients undergoing secukinumab: a real-life, multicenter retrospective observational study.

Geographic tongue (GT), a form of inverse psoriasis, is frequently linked to plaque psoriasis. The objective of the study is to evaluate IL-17 blocker (secukinumab) effect on GT severity. This reallife, multicenter, retrospective observational pilot study evaluated patients with plaque psoriasis and concomitant GT that started in label treatment with secukinumab. Patients were evaluated twice (T0=baseline and T1=after 16 weeks) by a dentist and a dermatologist collecting data on cutaneous Psoriasis Area Severity Index (PASI) and oral statuses using Hume's classification of the Geographic Tongue Severity Index (GTASI). Twenty-nine psoriatic patients with GT treated with secukinumab were enrolled for the study. Seventeen patients display type I GT, 6 type II and 6 type III with an overall GTASI of 25.52±9.57 at the baseline (T0). No correlation was found between delta GTASI and delta PASI (r=-0.27, p=0.1551). GTASI decrement from T0 to T1 was statistically significant ([95%CI -26.64 to -19.56], t=-13.36, p<0.0001). Secukinumab may enter in GT therapeutic armamentarium as the first biologic IL-17 blocker in patients with concomitant moderate-to-severe plaque psoriasis.

Cutaneous and oral comorbidities in patients with geographic tongue: a multicenter multidisciplinary cross-sectional observational study.

Geographic tongue (GT) represents a localized type of psoriasis inversa and its burden of dermatological and oral comorbidities frequently conditions its severity and diagnosis. Currently, no epidemiological studies have evaluated GT muco-cutaneous comorbidities. We aimed to study oral and dermatological comorbidities in a large sample of GT patients. In this multicenter, cross-sectional study, involving 4 primary referral centers in Italy, we evaluated adult GT patients, who were assessed by board certified dermatologists and dentists for 5 months and collected demographics and medical history. GT was evaluated using Hume's classification together with Geographic tongue severity index (GTASI) to score its severity. The prevalence of oral and dermatological comorbidities was recorded. In the sample we enrolled 137 GT patients (M/F= 5:1) with a mean age of 48,2 ± 14,7 yoa and 33.6% had GT family history. The clinical evaluation found 96 (70.1%) GT type I, 7 (5.1%) type II, 13 (9.5%) type IIIa, 19 (13.9%) type IIIb, 2 (1.5%) type IV, following Hume's classification. The mean GTASI score was 23,7 ± 14,2 and the vast majority displayed a severe form of GT. Eighty-nine patients had oral comorbidities (burning mouth syndrome, caries, parulid and lichen planus) and 80 had dermatological concurrent conditions (plaque psoriasis, inverse psoriasis and atopic dermatitis). In GT patients, both dermatological and dental evaluation should be mandatory to identify previously undiagnosed mucocutaneous comorbidities.

Implications of crop model ensemble size and composition for estimates of adaptation effects and agreement of recommendations.

Climate change is expected to severely affect cropping systems and food production in many parts of the world unless local adaptation can ameliorate these impacts. Ensembles of crop simulation models can be useful tools for assessing if proposed adaptation options are capable of achieving target yields, whilst also quantifying the share of uncertainty in the simulated crop impact resulting from the crop models themselves. Although some studies have analysed the influence of ensemble size on model outcomes, the effect of ensemble composition has not yet been properly appraised. Moreover, results and derived recommendations typically rely on averaged ensemble simulation results without accounting sufficiently for the spread of model outcomes. Therefore, we developed an Ensemble Outcome Agreement (EOA) index, which analyses the effect of changes in composition and size of a multi-model ensemble (MME) to evaluate the level of agreement between MME outcomes with respect to a given hypothesis (e.g. that adaptation measures result in positive crop responses). We analysed the recommendations of a previous study performed with an ensemble of 17 crop models and testing 54 adaptation options for rainfed winter wheat (Triticum aestivum L.) at Lleida (NE Spain) under perturbed conditions of temperature, precipitation and atmospheric CO2 concentration. Our results confirmed that most adaptations recommended in the previous study have a positive effect. However, we also showed that some options did not remain recommendable in specific conditions if different ensembles were considered. Using EOA, we were able to identify the adaptation options for which there is high confidence in their effectiveness at enhancing yields, even under severe climate perturbations. These include substituting spring wheat for winter wheat combined with earlier sowing dates and standard or longer duration cultivars, or introducing supplementary irrigation, the latter increasing EOA values in all cases. There is low confidence in recovering yields to baseline levels, although this target could be attained for some adaptation options under moderate climate perturbations. Recommendations derived from such robust results may provide crucial information for stakeholders seeking to implement adaptation measures.

promSEMBLE: Hard Pattern Mining and Ensemble Learning for Detecting DNA Promoter Sequences.

Accurate identification of DNA promoter sequences is of crucial importance in unraveling the underlying mechanisms that regulate gene transcription. Initiation of transcription is controlled through regulatory transcription factors binding to promoter core regions in the DNA sequence. Detection of promoter regions is necessary if we are to build genetic regulatory networks for biomedical and clinical applications, and for identification of rarely expressed genes. We propose a novel ensemble learning technique using deep recurrent neural networks with convolutional feature extraction and hard negative pattern mining to detect several types of promoter sequences, including promoter sequences with the TATA-box and without the TATA-box, within DNA sequences of four different species. Using extensive independent tests and previously published results, we demonstrate that our method sets a new state-of-the-art of over 98% Matthews correlation coefficient in all eight organism categories for recognizing the stretch of base pairs that code for the promoter region within DNA sequences.

Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver transplant surgery: a prospective randomized control study.

BACKGROUND: Although orthotopic liver transplantation (OLT) is nowadays considered standard practice at experienced centres, it can still be affected by a significant risk of massive bleeding and its related complications. Solvent/detergent plasma (S/D Plasma) has been proposed as an alternative to fresh frozen plasma (FFP) to curtail such complications. This study aimed at evaluating the efficacy of S/D Plasma in OLT patients by comparing it to FFP. MATERIALS AND METHODS: Sixty-three OLT patients were randomized into two groups depending on whether they were transfused with FFP or S/D plasma. A thromboelastography-based protocol aimed at achieving and maintaining predetermined coagulation goals was used to guide plasma transfusions. At the beginning and the end of surgery, standard laboratory coagulation tests were performed together with the assessment of the VII, VIII, V, XII factors and S protein blood levels. RESULTS: The two study groups equally achieved the thromboelastography goals but with a reduced amount of transfusions in the S/D plasma group (P < 0.0001). At the end of surgery, factors V and XII and S protein blood levels were lower in the S/D plasma patients who also showed lower INR, aPTT and antithrombin III levels. CONCLUSION: In cirrhotic patients undergoing OLT, the use of S\D plasma associated with thromboelastography allows the same clinical results but with a significant reduction in the amount of plasma transfusions.

Changes in salivary flow rate and pH in pregnancy.

OBJECTIVE: To evaluate changes in pH and Flow Rate (FR) of the Unstimulated Whole Saliva (UWS) in a sample of pregnant women in different gestational periods. PATIENTS AND METHODS: After collecting demographic data and medical histories, as well as conducting an oral examination, a sample of pregnant women were instructed on how to prepare prior to the sample collection. At a time between 11.00 and 12.00 a.m., they were subjected to salivary collection (spitting method, time 5 minutes); the measurement of FR was carried out using a professionally calibrated precision scale and the pH with a portable pH meter. RESULTS: The average FR of the women's detected sample (0.40 ± 0.20 ml/min) was lower than that of non-pregnant women (0.48 ± 0.15 ml/min) of the same age (p <0.05). We observed an increase (p <0.001) of FR in the first trimester (0.56 ± 0.20 ml/min) compared to second (0.34 ± 0.14 ml/min) and third (0.31 ± 0.14 ml/min) trimester. The salivary pH of pregnant women was lower than the one detected in the non-pregnant women's sample (p <0.0001). CONCLUSIONS: Our study highlighted an increase in the FR in the first trimester compared to that detected in the second and third trimesters of pregnancy which viceversa was lower than the average FR in non-pregnant women. This data, combined with the decrease in salivary pH, supports the hypothesis that correlates the FR increase with the attempt to counter the decrease in pH due to gastric regurgitation frequent in the first trimester. Further studies are necessary to evaluate salivary FR and pH in pregnant women samples related to the emesis phenomenon.

The human imperative of stabilizing global climate change at 1.5°C.

Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.

Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion.

BRAF and CRAF are critical components of the MAPK signaling pathway which is activated in many cancer types. In approximately 1% of melanomas, BRAF or CRAF are activated through structural arrangements. We describe here a metastatic melanoma with a GOLGA4-RAF1 fusion and pathogenic variants in CTNNB1 and CDKN2A. Anti-CTLA4/anti-PD1 combination immunotherapy failed to control tumor progression. In the absence of other actionable variants the patient was administered MEK inhibitor therapy on the basis of its potential action against RAF1 fusions. This resulted in a profound and clinically significant response. We demonstrated that GOLGA4-RAF1 expression was associated with ERK activation, elevated expression of the RAS/RAF downstream co-effector ETV5, and a high Ki67 index. These findings provide a rationale for the dramatic response to targeted therapy. This study shows that thorough molecular characterization of treatment-resistant cancers can identify therapeutic targets and personalize management, leading to improved patient outcomes.

Wound healing from a cellular stress response perspective.

This meeting review highlights areas of mutual interest to investigators in the cellular stress response field and to those carrying out wound-healing research. Inflammation, perhaps the major unifying theme of this meeting, is an essential component of the adult wound response and understanding the control of inflammation is a common interest shared with researchers of the cellular stress response. The particular interest of the authors of this review is in chronic non-healing wounds that frequently occur in patients with major illnesses such as diabetes and diseases of the blood vessels. This orientation has undoubtedly influenced the selection of topics. It is fair to say that the authors were often surprised and certainly impressed with the overlapping interests and possibilities for collaboration among investigators of these two research areas.

Transcranial doppler sonography is useful for the decision-making at the point of care in patients with acute hepatic failure: a single centre's experience.

Acute hepatic failure (ALF) is an uncommon disease characterized by a rapid deterioration of the hepatic function with severe derangements of the mental status in previously healthy subjects due to massive hepatocytes necrosis. Neurological impairment, due to intracranial hypertension and cerebral ischemia, is a key factor because it is a main criterion to decide when to proceed to liver transplantation, which is only treatment for these patients. Therefore, neurological monitoring holds an essential role in the clinical management of ALF patients but it needs to be performed at the point-of-care in the majority of the cases as such critically ill patients cannot be moved away from the ICU because they frequently need continuous hemodynamic, ventilatory and renal support. We herein report and discuss our experience relating to the use of transcranial sonography as a neuro-monitoring tool in ALF patients. In our series this technique allowed a repeatable and reliable non-invasive assessment of cerebral blood flow changes at the bedside thus avoiding the complications associated with the use of an intracranial probe to measure intra-cranial pressure and making it possible to correctly evaluate the timing and feasibility of liver transplantation.

[Extramedullary hematopoyesis: compensatory mechanism or clinic syndrome? Case report and review of literature]. / Hematopoyesis extramedular: ¿mecanismo compensador o síndrome clínico? Descripción de un caso y revisión bibliográfica.

Extramedullary hematopoiesis (EMH) is a compensatory mechanism occurring in patients with chronic anemia. Liver, spleen, and lymph nodes are frequently involved. However, EMH may also develop in several sites such as thymus, kidneys, retroperitoneum, paravertebral areas of the thorax, lungs, bowel and others. Rarely symptomatic, it often shows a variety of clinical features. This condition, frequently, may be fatal. A correct early diagnosis of EHM might avoid, if possible, a bad prognosis. The Authors report a case where bone marrow cells were identified in centrifuge cerebrospinal fluid of a patient suffering from non-Hodgkin lymphoma.

The healthcare system and the provision of oral healthcare in European Union member states. Part 8: Italy.

In Italy healthcare is provided for all Italian citizens and residents and it is delivered mainly by public providers, with some private or private-public entities. Italy's public healthcare system - the Servizio Sanitario Nazionale (SSN) - is organised by the Ministry of Health and administered on a devolved regional basis. It is financed by general taxation that provides universal coverage, largely free of charge at the point of service. The central government establishes the basic national health benefits package, which must be uniformly provided throughout the country, through services guaranteed under the NHS provision called LEA - (Livelli Essenziali di Assistenza [Essential Level of Assistance]) and allocates national funds to the regions. The regions, through their regional health departments, are responsible for organising, administering and delivering primary, secondary and tertiary healthcare services as well as preventive and health promotion services. Regions are allowed a large degree of autonomy in how they perform this role and regarding decisions about the local structure of the system. Complementary and supplementary private health insurance is also available. However, as in most other Mediterranean European countries, in Italy oral healthcare is mainly provided under private arrangements. The public healthcare system provides only 5-8% of oral healthcare services and this percentage varies from region to region. Oral healthcare is included in the Legislation on Essential levels of care (LEAs) for specific populations such as children, vulnerable people (medically compromised and those on low income) and individuals who need oral healthcare in some urgent/emergency cases. For other people, oral healthcare is generally not covered. Apart from the national benefits package, regions may also carry out their own initiatives autonomously, but must finance these themselves. The number of dentists working in Italy has grown rapidly in the last few years. In December 2014, there were 59,324 practicing dentists with a ratio of one dentist every 1025 inhabitants, about 90,000 dental chair-side assistants, about 26,000 dental technicians and about 4000 dental hygienists. To enrol in an Italian dental school a student must pass a competitive national entrance examination after obtaining a high school leaving certificate. For entry in the 2015-2016 cycle, there were 792 places for dentistry. In comparison with dental schools in other EU member states, the number of dental students per school is low with an average of 20 students per year, per school and a range of 10 to 60. The aims of this paper are to give a brief description of the organisation of healthcare in Italy, to outline the system for the provision of oral healthcare in Italy and to explain and discuss the latest changes.

Is solvent/detergent plasma better than standard fresh-frozen plasma? A systematic review and an expert consensus document.

BACKGROUND: Only a few studies have compared solvent/detergent plasma (SD-plasma) to standard fresh-frozen plasma (FFP) in terms of efficacy and safety. MATERIALS AND METHODS: A systematic review was performed in order to develop a consensus document on the use of SD-plasma. Moreover, a pharmacoeconomic study was performed in order to assess whether the use of SD-plasma can be cost-effective with respect to the use of FFP. A multidisciplinary panel used the systematic review and the GRADE methodology to develop evidence-based recommendations on this topic. RESULTS: Based on moderate to very low quality evidence, the panel developed the following consensus statements: (i) the panel suggested that SD-plasma is safer than FFP; (ii) the panel could not express for or against a greater efficacy of SD-plasma as compared to FFP; (iii) the panel suggested that in patients undergoing liver transplantation SD-plasma can be preferred over FFP; (iv) the panel suggested that SD-plasma can be preferred over FFP in patients with thrombotic thrombocytopenic purpura undergoing plasma-exchange procedures; (v) the panel could not recommend for or against preferring SD-plasma over FFP in critical care patients; and (vi) the panel suggested that the use of SD-plasma can be cost-effective with respect to the use of FFP. DISCUSSION: Data from additional randomised studies are needed to establish more definitive guidelines on the use of SD-plasma.

A role for tumor markers in therapeutic decisions after chemotherapy induction of objective remission in stage III epithelial ovarian neoplasms.

The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second-look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- less than 1 cm., that is, neoplastic localizations reliable for consolidation radiation therapy.

Intraabdominal pressure in liver transplant recipients: incidence and clinical significance.

BACKGROUND: The incidence and clinical relevance of increased intraabdominal pressure after orthotopic liver transplantation (OLT) has not yet been evaluated despite the finding that occurrence of this condition in postsurgical critically ill patients may impair various organ functions. The aim of this study was to assess whether the occurrence of abdominal hypertension among a population of OLT recipients was an important cofactor producing early postoperative complications. METHOD: This prospective clinical study measured abdominal pressure every 6 hours during the intensive care unit (ICU) stay using the urinary bladder method. A value of >/=25 mm Hg was considered high. Hemodynamic status was simultaneously evaluated and renal function assessed based on the hourly urinary output, and by calculating serum creatinine on postoperative days 2 and 4. Renal failure was defined as a serum creatinine level of >1.5 mg/dL, or an increase in peak of >1 mg/L within 72 hours of surgery. The filtration gradient and patient outcomes were also considered. RESULTS: Intraabdominal hypertension was observed in 32% of cases. The subjects displaying high IAP showed significantly lower artery pressure values (P <.01), but did not differ in terms of central venous pressure or cardiac output. High intraabdominal pressure was more frequently associated with renal failure (P <.01), a lower filtration gradient (P <.001), delayed postsurgical weaning from the ventilation (P <.001), and increased ICU mortality (P <.05). A receiver operator characteristic curve analysis showed that the critical IAP values, namely those with the best sensitivity/specificity, were 23 mm Hg for postoperative ventilatory delayed weaning (P <.05), 24 mm Hg for renal dysfunction (P <.05), and 25 mm Hg for death (P <.01). CONCLUSIONS: Abdominal hypertension occurs frequently after OLT and may be associated with a complicated postoperative course.

Intracavitary cisplatin in malignant cardiac tamponade.

A case of lung cancer presenting with cardiac tamponade is reported. Lasting control of the malignant effusion was achieved by means of intracavitary cisplatin following pericardiocentesis. The patient presented an objective response to subsequent systemic chemotherapy and died 10 months after the diagnosis because of disseminated cancer, without clinical or instrumental findings of pericardial effusion.

Unfavorable experience with hypofractionated radiotherapy in unresectable lung cancer.

The use of a reduced number of large-sized fractions in radiotherapy (hypofractionation) is usually associated with poor therapeutic results and severe adverse effects, in accord with radiobiologic concepts. However by some authors unresectable lung cancer patients have been treated with hypofractionated radiotherapy with the main aim of "convenience". Result and damage rates are reported to be comparable to those of conventional treatment. In our experience, based on palliative irradiation of 86 advanced-stage, nonmicrocytoma patients, objective remission rates, subjective and performance status improvement, and survival overall were as poor as could be expected in this kind of presentation, with no striking impact of this treatment modality. Severe adverse effects were shown by a large proportion of cases involving skin and soft tissues of the chest wall (40%) and lungs (55.5%). The incidence of severe damage was in agreement with BED (biologic effective dose) values, differently from other experiences of radiotherapeutic management of advanced lung cancer with large fractions.