Debris flows in the eastern Italian Alps: seasonality and atmospheric circulation patterns

Abstract. The work examines the seasonality and large-scale atmospheric circulation patterns associated with debris-flow occurrence in the Trentino–Alto Adige region (eastern Italian Alps). Analysis is based on classification algorithms applied to a uniquely dense archive of debris flows and hourly rain gauge precipitation series covering the period 2000–2009. Results highlight the seasonal and synoptic forcing patterns linked to debris flows in the study area. Summer and fall season account for 92% of the debris flows in the record, while atmospheric circulation characterized by zonal west, mixed and meridional south and southeast (SE–S) patterns account for 80%. Both seasonal and circulation patterns exhibit geographical preference. In the case of seasonality, there is a strong north–south separation of summer–fall dominance, while spatial distribution of dominant circulation patterns exhibits clustering, with both zonal west and mixed patterns prevailing in the northwest and central east part of the region, while the southern part relates to meridional south and southeast pattern. Seasonal and synoptic pattern dependence is pronounced also on the debris-flow-triggering rainfall properties. Examination of rainfall intensity–duration thresholds derived for different data classes (according to season and synoptic pattern) revealed a distinct variability in estimated thresholds. These findings imply a certain control on debris-flow events and can therefore be used to improve existing alert systems

Brief Communication: A new testing field for debris flow warning systems

Abstract. A permanent field installation for the systematic test of debris flow warning systems and algorithms has been equipped on the eastern Italian Alps. The installation was also designed to produce didactic videos and it may host informative visits. The populace education is essential and should be envisaged in planning any research on hazard mitigation interventions: this new installation responds to this requirement and offers an example of integration between technical and informative needs. The occurrence of a debris flow in 2014 allowed the first tests of a new warning system under development and to record an informative video on its performances. This paper will provide a description of the installation and an account of the first technical and informative results obtained

Neuromuscular electrical stimulation restores upper limb sensory-motor functions and body representations in chronic stroke survivors

Background: A conventional treatment outcome is suboptimal for sensory impairments in stroke patients. Novel approaches based on electrical stimulation or robotics are proposed as an adjuvant for rehabilitation, though their efficacy for motor, sensory, and body representation recovery have not been tested. Methods: Sixty chronic stroke patients with unilateral motor deficits were included in a pseudo-randomized open-label multi-arm control trial (ClinicalTrials.gov: NCT03349138). We tested the effects of a robotic glove (GloReha [GR]) and a new neuromuscular electrical stimulation system (Helping Hand [HH]) and compared them with conventional treatment (CT) in restoring motor and sensory functions and the affected limb perception. HH was designed to concurrently deliver peripheral motor activation and enhanced cutaneous sensation. Patients were split in four dose-matched groups: CT, GR, HH, and GRHH (receiving 50% GR and 50% HH). Assessments were performed at inclusion, halfway, end of treatment (week 9), and follow-up (week 13). Findings: HH provided an earlier benefit, quantified by the Motricity Index (MI), than GR. At the end of the treatment, the amelioration was higher in groups GRHH and HH and extended to somatosensory functions. These benefits persisted at the follow-up. GRHH and HH also improved the perceived dimensions and altered feeling toward the affected limb. Interestingly, the reduction of altered feelings correlated with MI improvements and depended on the amount of HH. Conclusions: We suggest that HH concurrently stimulates sensory and motor systems by generating an enhanced cutaneous sensation, coherent in location with the elicited motor recruitment, leading to ameliorated sensorimotor functions and bodily perceptions in stroke patients. Funding: This work was supported by a Foundation advised by CARIGEST, by Fondazione CARIPLO, by the SNSF NCCR Robotics, and by the Bertarelli Foundation

Role of neuronal and inducible nitric oxide synthases in the guinea pig ileum myenteric plexus during in vitro ischemia and reperfusion

Background Intestinal ischemia and reperfusion (I/R) injury leads to abnormalities in motility, namely delay of transit, caused by damage to myenteric neurons. Alterations of the nitrergic transmission may occur in these conditions. This study investigated whether an in vitro I/R injury may affect nitric oxide (NO) production from the myenteric plexus of the guinea pig ileum and which NO synthase (NOS) isoform is involved. Methods The distribution of the neuronal (n) and inducible (i) NOS was determined by immunohistochemistry during 60 min of glucose/oxygen deprivation (in vitro ischemia) followed by 60 min of reperfusion. The protein and mRNA levels of nNOS and iNOS were investigated by Westernimmunoblotting and real time RT-PCR, respectively. NO levels were quantified as nitrite/nitrate. Key Results After in vitro I/R the proportion of nNOSexpressing neurons and protein levels remained unchanged. nNOS mRNA levels increased 60 min after inducing ischemia and in the following 5 min of reperfusion. iNOS-immunoreactive neurons, protein and mRNA levels were up-regulated during the whole I/R period. A significant increase of nitrite/nitrate levels was observed in the first 5 min after inducing I/R and was significantly reduced by Nx-propyl-L-arginine and 1400 W, selective inhibitors of nNOS and iNOS, respectively. Conclusions & Inferences Our data demonstrate that both iNOS and nNOS represent sources for NO overproduction in ileal myenteric plexus during I/R, although iNOS undergoes more consistent changes suggesting a more relevant role for this isoform in the alterations occurring in myenteric neurons following I/R

Interpretation and the Constraints on International Courts

This paper argues that methodologies of interpretation do not do what they promise – they do not constrain interpretation by providing neutral steps that one can follow in finding out a meaning of a text – but nevertheless do their constraining work by being part of what can be described as the legal practice

Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice

Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF-and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity

Mutational profile of TP53 in esophageal squamous cell carcinoma associated with chagasic megaesophagus

Chaga's disease is an important communicable neglected disease that is gaining wider attention due to its increasing incidence worldwide. Achalasia due to chagasic megaesophagus (CM), a complication of this disease, is a known-yet, poorly understood-etiological factor for esophageal squamous cell carcinoma (ESCC) development. In this study, we aimed to perform the analysis of TP53 mutations in a series of Brazilian patients with ESCC that developed in the context CM (ESCC/CM), and to compare with the TP53 mutation profile of patients with benign CM and patients with nonchagasic ESCC. Additionally, we intended to correlate the TP53 mutation results with patient's clinical pathological features. By polymerase chain reaction (PCR) followed by direct sequencing of the hotspot regions of TP53 (exon 5 to 8), we found that TP53 mutations were present in 40.6% (13/32) of the ESCC/CM group, 45% (18/40) of the nonchagasic ESCC group, and in only 3% (1/33) of the benign CM group. Missense mutations were the most common in the three groups, yet, the type and mutated exon mutation varied significantly among the groups. Clinically, the groups exhibited distinct features, with both cancer groups (ESCC and ESCC/CM) been significantly associated higher consumption of alcohol and tobacco, older age, worse Karnofsky performance status, poor outcome than the patients with benign CM. No significant association was found between TP53 mutation profile and clinical-pathological features in any of the three groups. We describe first the time the analysis of TP53 mutations in ESCC that developed in the context of CM, and the observed high frequency of mutations, suggest that TP53 also plays an important role in the tumorigenic process of this unexplored etiological condition.Supported by Barretos Cancer Hospital internal research funds (PAIP). Rui M Reis is recipient of a CNPq Produtividade em Pesquisa grantinfo:eu-repo/semantics/publishedVersio

Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer’s dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis

MRI texture analysis of subchondral bone at the tibial plateau

OBJECTIVES: To determine the feasibility of MRI texture analysis as a method of quantifying subchondral bone architecture in knee osteoarthritis (OA).   METHODS: Asymptomatic subjects aged 20-30 (group 1, n = 10), symptomatic patients aged 40-50 (group 2, n = 10) and patients scheduled for knee replacement aged 55-85 (group 3, n = 10) underwent high spatial resolution T1-weighted coronal 3T knee MRI. Regions of interest were created in the medial (MT) and lateral (LT) tibial subchondral bone from which 20 texture parameters were calculated. T2 mapping of the tibial cartilage was performed in groups 1 and 2. Mean parameter values were compared between groups using ANOVA. Linear discriminant analysis (LDA) was used to evaluate the ability of texture analysis to classify subjects correctly.   RESULTS: Significant differences in 18/20 and 12/20 subchondral bone texture parameters were demonstrated between groups at the MT and LT respectively. There was no significant difference in mean MT or LT cartilage T2 values between group 1 and group 2. LDA demonstrated subject classification accuracy of 97 % (95 % CI 91-100 %).   CONCLUSION: MRI texture analysis of tibial subchondral bone may allow detection of alteration in subchondral bone architecture in OA. This has potential applications in understanding OA pathogenesis and assessing response to treatment.   KEY POINTS: • Improved techniques to monitor OA disease progression and treatment response are desirable • Subchondral bone (SB) may play significant role in the development of OA • MRI texture analysis is a method of quantifying changes in SB architecture • Pilot study showed that this technique is feasible and reliable • Significant differences in SB texture were demonstrated between individuals with/without OA