Urban mobility and freight distribution service: best practices and lessons learnt in the MEROPE Interreg III B project

MEROPE (Telematic instruments for innovative services for mobility and logistic in urban and metropolitan areas), an INTERREG III B MEDOCC (Western Mediterranean) area project, started in September 2002 and ended in October 2004. In particular MEROPE addressed axis 3 - Transport Systems and Information Society; Measure 3.4 - Innovative communication and information technologies for the development of the territory. MEROPE’s overall objective was to investigate and develop evaluation models and telematic instruments to manage mobility and logistics in urban and metropolitan areas, in order to promote the development and application of innovative Information and Communication Technology (ICT) in support of integrated transport systems. A total of 14 cities were involved in the project, between them carrying out 9 study projects and 7 demonstration projects oriented towards the analysis and definition of mobility, transport and logistics chain features, with particular attention to their impacts in terms of environment, sustainability and competitiveness. This paper presents the development of the Merope project both at interregional level and in terms of the work carried out in each local site. Rather that a straightforward description of the work, however, it concentrates largely on an analysis of the project’s best practices and added value. As the project is now closed both in terms of activities and financial management, its current importance lies in its sustainability and transferability. Thus this paper will analyse the innovative actions carried out in Merope, within the general economic, social and political context of mobility and logistics, in order to identify what Merope has brought to the sector and what indeed remains to be done

Multi-services agency for the integrated management of mobility and of accessibility to transport services

AGATA (Multi-services agency based on telecommunication centres for the integrated management of mobility and of accessibility to transport services) is an INTERREG III B MEDOCC area project, which began in July 2004 and will last until June 2006. The AGATA consortium of 8 partners from 3 European countries (Italy, Spain and Portugal) and one South Mediterranean country (Morocco), works towards the development of a multi-service agency which coordinates flexible transport and mobility services in urban and rural areas. This agency will be based on modern information and communication technologies, and composed of a network of services facilitating interactions between actors and agency. The project represents an example of transfer from the world of research to public administrations and transport companies, based on IST IV FP projects. AGATA’s goals are: successful undertaking of feasibility studies and pilot projects, the results of which will be widely diffused, exchange of experiences and best practices, identification of a business model for an ICT based telecommunication centre. AGATA was born in a context of growing mobility problems which this paper considers before going on to describe various different actions (studies, pilot actions, experiences exchange, results diffusion and promotion), which are currently being carried out both at a general project level and at a local level by the different partners. The results of these actions should in theory have an impact on the local environment and on the issues of transport and mobility on a wider scale. This paper shows the expected results and evaluation techniques and the possible future of such initiatives in political and financial terms

Unexpected death of a ventilator-dependent amyotrophic lateral sclerosis patient

Background: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive, neurodegenerative disease and most patients affected die of respiratory compromise and/or pneumonia within 2â3 years of diagnosis. As ALS progresses, ventilator assistance is required. In the end stages of the disease, patients suffer from respiratory failure and may become ventilator-dependent. Deaths due to malfunction of mechanical ventilators are reported but there are very few forensic autopsy records. We report the case of a 69-year-old ALS female ventilator-dependent, trachostomised patient who was found dead by her husband, with the ventilator in âstand-byâ mode. Method: A forensic autopsy was performed. Samples of internal organs were taken for histological and toxicological examination. The ventilator internal memory was also analysed and tested in order to find possible malfunction. Results: Gross examination did not reveal any sign of trauma but showed brain and lung congestion. Pulmonary histological examination revealed thickening of peribronchial interstitial space, alveolar over-distension, break of inter-alveolar walls and diffuse alveolar haemorrhages. Focal microhemorrhages were also detected in other organs. Analysis of the ventilator internal memory showed that during the night of death, there had been several voltage drops. Specific tests revealed malfunction of the internal battery which was unable to provide the necessary voltage, as a consequence the ventilator switched off, stopping ventilation. Battery malfunction reduced the volume of the ventilator alarm, which was not heard by the caregiver. Conclusion: Histological pattern, with acute pulmonary emphysema and focal polivisceral haemorrhages, is strongly suggestive of a death due to âacuteâ asphyxia. The authors also discuss the need for strict supervision and follow up of these ventilatory dependent patients and their devices. Resumo: Introdução: A Esclerose Lateral Amiotrófica (ELA) é uma doença fatal, progressiva e neurodegenerativa e a maioria dos doentes afectados morrerão de falha respiratória e/ou pneumonia 2 ou 3 anos após o diagnóstico. à medida que a ELA progride torna-se necessária a assistência ventilatória. Nos estágios finais da doença, os doentes sofrem de insuficiência respiratória e podem tornar-se dependentes do ventilador. São conhecidas mortes devido ao mau funcionamento de ventiladores mecânicos mas existem poucos registos forenses de tal situação. Relatamos o caso de uma doente de 69 anos com ELA, traqueostomizada e dependente do ventilador, que foi encontrada morta pelo seu marido com o ventilador em modo de espera («stand-by»). Método: Foi realizada uma autópsia forense. Foram recolhidas amostras dos órgãos internos para exame toxicológico e histológico. A memória interna do ventilador foi também analisada e testada de modo a descobrir uma possível avaria. Resultados: O exame macroscópico não revelou qualquer sinal de trauma mas indicou congestão cerebral e pulmonar. O exame pulmonar histológico revelou o espessamento do espaço intersticial peribrônquico, sobredistensão alveolar, quebra de paredes interalveolares e hemorragias alveolares difusas. Foram detetadas micro-hemorragias focais noutros órgãos. A análise da memória interna do ventilador mostrou que, durante a noite da morte, houve diversas quedas de tensão. Testes específicos revelaram o mau funcionamento da bateria interna que não conseguiu fornecer a tensão necessária, consequentemente o ventilador desligou-se, parando a ventilação. O mau funcionamento da bateria reduziu o volume do alarme do ventilador, que não foi ouvido pelo prestador de cuidados. Conclusão: O padrão histológico, com enfisema pulmonar agudo e hemorragias focais poliviscerais, é fortemente indicador de morte devido a asfixia «aguda». Os autores discutem também a necessidade de uma supervisão rigorosa e seguimento destes doentes dependentes do ventilador e dos seus equipamentos. Keywords: Amyotrophic lateral sclerosis, Acute respiratory failure, Home mechanical ventilation, Palavras-chave: Esclerose lateral amiotrófica, Insuficiência respiratória aguda, Ventilação mecânica doméstic

Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of Kv7.2 potassium channel subunits

Mutations in the K(V)7.2 gene encoding for voltage-dependent K(+) channel subunits cause neonatal epilepsies with wide phenotypic heterogeneity. Two mutations affecting the same positively charged residue in the S(4) domain of K(V)7.2 have been found in children affected with benign familial neonatal seizures (R213W mutation) or with neonatal epileptic encephalopathy with severe pharmacoresistant seizures and neurocognitive delay, suppression-burst pattern at EEG, and distinct neuroradiological features (R213Q mutation). To examine the molecular basis for this strikingly different phenotype, we studied the functional characteristics of mutant channels by using electrophysiological techniques, computational modeling, and homology modeling. Functional studies revealed that, in homomeric or heteromeric configuration with K(V)7.2 and/or K(V)7.3 subunits, both mutations markedly destabilized the open state, causing a dramatic decrease in channel voltage sensitivity. These functional changes were (i) more pronounced for channels incorporating R213Q- than R213W-carrying K(V)7.2 subunits; (ii) proportional to the number of mutant subunits incorporated; and (iii) fully restored by the neuronal K(v)7 activator retigabine. Homology modeling confirmed a critical role for the R213 residue in stabilizing the activated voltage sensor configuration. Modeling experiments in CA1 hippocampal pyramidal cells revealed that both mutations increased cell firing frequency, with the R213Q mutation prompting more dramatic functional changes compared with the R213W mutation. These results suggest that the clinical disease severity may be related to the extent of the mutation-induced functional K(+) channel impairment, and set the preclinical basis for the potential use of K(v)7 openers as a targeted anticonvulsant therapy to improve developmental outcome in neonates with K(V)7.2 encephalopathy

Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine

Despite the availability of over 20 antiepileptic drugs, about 30% of epileptic patients do not achieve seizure control. Thus, identification of additional molecules targeting novel molecular mechanisms is a primary effort in today’s antiepileptic drug research. This paper reviews the pharmacological development of retigabine, an antiepileptic drug with a novel mechanism of action, namely the activation of voltage-gated potassium channels of the Kv7 subfamily. These channels, which act as widespread regulators of intrinsic neuronal excitability and of neurotransmitter-induced network excitability changes, are currently viewed among the most promising targets for anticonvulsant pharmacotherapy. In particular, the present work reviews the pathophysiological role of Kv7 channels in neuronal function, the molecular mechanisms involved in the Kv7 channel-opening action of retigabine, the activity of retigabine in preclinical in vitro and in vivo studies predictive of anticonvulsant activities, and the clinical status of development for this drug as an add-on treatment for pharmacoresistant epilepsy. Particular efforts are devoted to highlighting the potential advantages and disadvantages of retigabine when compared with currently available compounds, in order to provide a comprehensive assessment of its role in therapy for treatment-resistant epilepsies

Cardiovascular risk markers in patients with primary aldosteronism: A systematic review and meta-analysis of literature studies

Background/objectives: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with primary aldosteronism (PA). We performed a meta-analysis on the impact of PA on major markers of CV risk. Methods: Studies on the relationship between PA and common carotid artery intima-media thickness (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), pulse-wave velocity (PWV), augmentation index (AIx), and ankle-brachial index (ABI) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results: 12 case-control studies (445 cases, 472 controls) were included. Compared to subjects with essential hypertension (EH), PA patients showed a higher CCA-IMT (MD: 0.12 mm; 95% CI: 0.09, 0.16; P<0.00001), and a higher aortic-PWV (272 cases and 240 controls, MD: 1.39 m/s; 95% CI: 0.90, 1.87; P<0.00001). In contrast, non-significant differences were found in AIx and AIx normalized to a heart rate of 75 beats per minute (AIx@75). When compared to normotensive subjects, PA patients showed significantly higher CCA-IMT (MD: 0.16 mm; 95% CI: 0.05, 0.27; P=0.004), aortic-PWV (MD: 3.74 m/s; 95% CI: 3.43, 4.05; P<0.00001), AIx@75 (MD: 8.59%; 95% CI: 0.69, 16.50; P=0.03), and a significantly lower FMD (MD: -2.52%; 95% CI: -3.64, -1.40; P<0.0001). Sensitivity and subgroup analyses substantially confirmed our results. Metaregression models showed that male gender, diabetes, and smoking habit impact on the observed results. Conclusions: PA appears significantly associated with markers of subclinical atherosclerosis and CV risk. These findings could help establish more specific CV prevention strategies in this clinical setting

Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia: Systematic Review and Meta‐Analysis of Randomized Controlled Trials

n/

Unexpected delayed death after manual strangulation: need for careful examination in the emergency room

The aim of this case report was to demonstrate the importance of detailed clinical assessment in victims of attempted manual strangulation, to prevent the occurrence of delayed death due to an airway collapse; and to provide an update on clinical management of these patients. An elderly male patient presented with a sore throat and speech impairment after attempting manual strangulation. Physical examination showed reddish skin of the neck, an extensive haematoma of the hard palate and anterior tongue. Flexible laryngoscopy failed to show any swelling of the hypopharynx or larynx. A few hours after presentation, the patient developed acute dyspnoea and died. Autopsy and post-mortem CT scan showed a haematoma in the thyro-epiglottal space. In conclusion, victims of manual strangulation can survive despite internal neck injury which can lead to delayed fatal airway collapse. This is because often there are few or no signs of assault, therefore medical evaluation should be thorough and timely. Sometimes immediate tracheotomy can be life saving