Integrated Environmental Study for Beach Management: A Methodological Approach

This paper aims to present a project convened by the University of Genoa and Fondazione Eni Enrico Mattei (FEEM), in collaboration with Local Authorities, concerning the development of tools for beach management in the Riviera del Beigua (Liguria Region, Italy). The aim of the first step of the project is to assess the environmental state of resort beaches examining them interdisciplinary, through a data analysis based on a sound understanding of the components of the physical and the human system. The following step will be the treatment of the data, through the use of various instruments, which use a synthesis analysis, such as the traditional SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis, and the use of a set of environmental and socio-economic indicators. Finally, our ultimate target is to propose guidelines, which will supply an instrument to back up policies concerning beach planning and management.Costal management, Sustainable tourist, Integrated assessment, Indicators

High-Resolution Transperineal Ultrasound in Anorectal Malformations—Can We Replace the Distal Colostogram?

Introduction Anorectal malformations (ARM) affect 1 in 5,000 newborns with a wide range of defects. In the absence of a visible fistula, the diagnosis and classification of ARM require an augmented pressure distal colostogram. This procedure can be done after a diverting colostomy has been performed and implies exposing the child to radiation. We hypothesized that high-resolution transperineal ultrasound could correctly diagnose the type of ARM, thus sparing radiation exposure. Case Description Four full-term male newborns with ARM and no visible anal opening were referred to our center for further management. A diverting descendostomy was performed in the first 48 hours of life in all cases. Prior to the reconstructive surgery, we performed a high-resolution transperineal ultrasound with 3D tomographic reconstruction of the perineal region to assess the urethra, the rectum, and a possible fistula. Findings were compared with a conventional augmented pressure distal colostogram. The image acquisition was fast and did not cause any additional distress to the children. Conclusion In all cases the results of the distal colostogram nicely correlated with the high-resolution transperineal ultrasound with 3D tomographic reconstruction. In the future, we envision a time when it can potentially replace the distal colostogram in preoperative assessment of ARM with no distress and exposure to radiation

Table_2_The “chicken-leg anastomosis”: Low-cost tissue-realistic simulation model for esophageal atresia training in pediatric surgery.docx

IntroductionShifting the training from the operating room (OR) to simulation models has been proven effective in enhancing patient safety and reducing the learning time to achieve competency and increase the operative efficiency. Currently the field of pediatric surgery only offers few low-cost trainers for specialized training and these feature predominantly artificial and often unrealistic tissue. The aim of this study was to develop an easy access low-cost tissue-realistic simulation model for open training of esophageal atresia and to evaluate the acceptance in trainees and junior pediatric surgeons.Materials and methodsThe model is fashioned using reconfigured chicken skin from a chicken leg. To create a model of esophageal atresia, the chicken skin is dissected off the muscle and reconfigured around a foley catheter balloon to recreate the proximal pouch and a feeding tube to recreate the distal pouch. Surrounding structures such as the tracheo-esophageal fistula and the azygos vein can be easily added, obtaining a realistic esophageal atresia (Type C) prototype. Evaluation of model construction, usage and impact on user were performed by both a self-assessment questionnaire with pre- and post-training questions as well as observer-based variables and a revised Objective Structured Assessment of Technical Skills (OSATS) score.ResultsA total of 10 participants were constructing and using the model at two different timepoints. OSATS score for overall performance was significantly higher (p = 0.005, z = −2.78) during the second observational period [median (MD): 4,95% confidence interval CI: 3.4, 5.1] compared to the first (MD: 3, 95% CI 2.4, 4.1). Self-reported boost in confidence after model usage for performing future esophageal atresia (EA) repair and bowel anastomosis (BA) in general was significantly higher (EA: U = 1, z = −2.3, p = 0.021, BA: U = 1, z = −2.41, p = 0.016) in participants with more years in training/attending status (EA MD:5, BA MD: 5.5) compared to less experienced participants (EA MD: 1.5, BA: 1).ConclusionOur easy access low-cost simulation model represents a feasible and tissue realistic training option to increase surgical performance of pediatric surgical trainees outside the OR.</p

Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case-control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response

On-Line Solid Phase Extraction High Performance Liquid Chromatography Method Coupled With Tandem Mass Spectrometry for the Therapeutic Monitoring of Cannabidiol and 7-Hydroxy-cannabidiol in Human Serum and Saliva

Cannabidiol is a novel antiseizure medication approved in Europe and the US for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex. We describe in this article a new and simple liquid chromatography-mass spectrometry method (LC-MS/MS) for the determination of cannabidiol and its active metabolite 7-hydroxy-cannabidiol in microvolumes of serum and saliva (50 mu l), to be used as a tool for therapeutic drug monitoring (TDM) and pharmacokinetic studies. After on-line solid phase extraction cannabidiol, 7-hydroxy-cannabidiol and the internal standard cannabidiol-d3 are separated on a monolithic C18 column under gradient conditions. Calibration curves are linear within the validated concentration range (10-1,000 ng/ml for cannabidiol and 5-500 ng/ml for 7-hydroxy-cannabidiol). The method is accurate (intraday and interday accuracy within 94-112% for cannabidiol, 91-109% for 7-hydroxy-cannabidiol), precise (intraday and interday precision <11.6% for cannabidiol and <11.7% for 7- hydroxy-cannabidiol) and sensitive, with a LOQ of 2.5 ng/ml for cannabidiol and 5 ng/ml for 7-hydroxy-cannabidiol. The stability of the analytes was confirmed under different storage conditions. Extraction recoveries were in the range of 81-129% for cannabidiol and 100-113% for 7-hydroxy-cannabidiol. The applicability of the method to TDM was demonstrated by analysis of human serum and saliva samples obtained from patients with epilepsy treated with cannabidiol

Therapeutic Salivary Monitoring of Perampanel in Patients with Epilepsy Using a Volumetric Absorptive Microsampling Technique

The objective of this study was to validate a novel assay using the volumetric absorptive microsampling (VAMS) technique combined with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the determination of the antiseizure medication perampanel in saliva and its clinical applicability in patients with epilepsy. VAMS tips were loaded with 30 μL of saliva and dried for 60 min. Analytes were extracted with methanol. The supernatant was evaporated under a gentle stream of nitrogen and reconstituted with 60 μL of methanol. Separation and quantification were achieved on a monolithic column connected to a mass spectrometer. Calibration curves were linear between 0.5 and 300 ng/mL. Intra- and inter-day accuracy was within 85.6–103.2% and intra-day and inter-day precision did not exceed 12.1%. Perampanel was stable in samples collected by VAMS and stored under different storage conditions. The VAMS-LC-MS/MS method was validated according to internationally accepted criteria and tested in patients with epilepsy who were receiving a combination of perampanel and other antiseizure medications. The method showed adequate bioanalytical performances, holding great potential as an alternative strategy to support domiciliary TDM in patients with epilepsy treated with perampanel according to the simplicity of sample collection

A Meta-Analysis to Estimate the Placebo Effect in Randomized Controlled Trials in Juvenile Idiopathic Arthritis

Objective To estimate the placebo effect in juvenile idiopathic arthritis (JIA) through a meta-analysis of phase III clinical trials with placebo comparator. Methods A systematic literature search was carried out up to December 2014. For parallel design studies the outcome was evaluated as a single 1-dimensional (1-D) variable or as a composite score; outcomes of withdrawal studies were evaluated only as composite scores. Results We included 26 of 224 trials (12%). In trials with parallel study design and a 1-D outcome, the placebo effect was 0.35 (95% confidence interval [95% CI] 0.27-0.43). Among trials with parallel study design and a composite score outcome, the placebo rate response was higher in trials that included patients with nonsystemic JIA (0.35 [95% CI 0.29-0.42]) than in trials that included only patients with systemic JIA (0.17 [95% CI 0.10-0.30]). In the withdrawal design trials, the percentages of patients receiving placebo who had disease flares during the double-blind phase were lower in trials that included patients with nonsystemic JIA (0.55 [95% CI 0.47-0.64]) than in trials that included only patients with systemic JIA (0.68 [95% CI 0.33-0.90]). Conclusion In trials with a parallel study design a sizable number of patients seem to benefit from a placebo effect, although this effect is smaller in patients with systemic JIA. In trials with a withdrawal design the inverse placebo effect is similar among the different JIA categories. This placebo effect should be considered when evaluating the effectiveness of proposed interventions and for future calculations of sample size

Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-&alpha;&beta;+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C&gt;A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment