PMC21 PATIENT-REPORTED OUTCOMES IN PRODUCT DEVELOPMENT GUIDANCE

Medina Campeny, XavierHomenatge a Mercè Rodoreda amb una reproducció del personatge de la Colometa, a la Plaça del Diamant, novel·la de l'escriptora. Al 1984 es va posar provisionalment a la pl. Rius i Taulet. Al 1990 es va traslladar a l'actual emplaçament

Natural vs. Anthropic influence on the multidecadal shoreline changes of mediterranean urban beaches: Lessons from the Gulf of Cagliari (Sardinia)

Urban Mediterranean beaches are often characterized by a fragile and unstable equilibrium that can be easily altered by ongoing climate change and by the increase in human pressure. This may pose serious threats to the survival of beach systems that cannot accommodate these modifications. In this paper, the spatio-temporal shift of the shoreline was investigated along two urban beaches in the Gulf of Cagliari (Poetto and Giorgino; southern Sardinia, western Mediterranean Sea) across a time frame of 62 years (1954–2016). The Digital Shoreline Analysis System (DSAS) ArcGIS™ extension was used to extract different statistical parameters which allowed us to quantify the erosion and accretion rates. These data were further examined in relation to a number of anthropic and natural forcings in order to disentangle the factors controlling shoreline evolution. Eight sectors with interchanging net erosive and accretion trends were identified along the Poetto and Giorgino beaches. In six decades, some sectors of the two study sites appeared to have undergone great shoreline modification as a result of the intense anthropogenic activities impacting these coastal areas. The westernmost portions of both beaches were found to be the most vulnerable to erosion processes; such conditions were likely controlled by the interplaying of local hydrodynamics and by the intense coastal development which affected these sectors. The highest retreat rates (mean end point rate (EPR) = −0.51/year) were recorded in the western limit of Giorgino beach. Along the western limit of Poetto beach, EPR erosion rates (mean EPR = −2.92/year) considerably increased in the years after the artificial beach nourishment carried out in 2002, suggesting that the majority of the nourished material was lost offshore or partly redistributed along the beach. Coastal structures, urban development, river catchment modification, industrial and port activities, beach cleaning and touristic and recreational activities have been identified as the ongoing causes of coastal alteration. If these factors remain constant, under projected climate change scenarios, these beaches are at risk of further increased flooding and erosion. In this context, the application of DSAS appeared as an essential tool, supporting a monitoring system able to provide understanding and, potentially, predictions of the short-to long-term evolution of these beach systems

Mortality and causes of death in patients with sporadic inclusion body myositis: Survey study based on the clinical experience of specialists in Australia, Europe and the USA

Background: There is a paucity of data on mortality and causes of death (CoDs) in patients with sporadic inclusion body myositis (sIBM), a rare, progressive, degenerative, inflammatory myopathy that typically affects those aged over 50 years. Objective: Based on patient records and expertise of clinical specialists, this study used questionnaires to evaluate physicians’ views on clinical characteristics of sIBM that may impact on premature mortality and CoDs in these patients. Methods: Thirteen physicians from seven countries completed two questionnaires online between December 20, 2012 and January 15, 2013. Responses to the first questionnaire were collated and presented in the second questionnaire to seek elaboration and identify consensus. Results: All 13 physicians completed both questionnaires, providing responses based on 585 living and 149 deceased patients under their care. Patients were reported to have experienced dysphagia (60.2%) and injurious falls (44.3%) during their disease. Over half of physicians reported that a subset of their patients with sIBM had a shortened lifespan (8/13), and agreed that bulbar dysfunction/dysphagia/oropharyngeal involvement (12/13), early-onset disease (8/13), severe symptoms (8/13), and falls (7/13) impacted lifespan. Factors related to sIBM were reported as CoDs in 40% of deceased patients. Oropharyngeal muscle dysfunction was ranked as the leading feature of sIBM that could contribute to death. The risk of premature mortality was higher than the age-matched comparison population. Conclusions: In the absence of data from traditional sources, this study suggests that features of sIBM may contribute to premature mortality and may be used to inform future studies

Label-Free Optical Detection of Biomolecular Translocation through Nanopore Arrays

In recent years, nanopores have emerged as exceptionally promising single-molecule sensors due to their ability to detect biomolecules at subfemtomole levels in a label-free manner. Development of a high-throughput nanopore-based biosensor requires multiplexing of nanopore measurements. Electrical detection, however, poses a challenge, as each nanopore circuit must be electrically independent, which requires complex nanofluidics and embedded electrodes. Here, we present an optical method for simultaneous measurements of the ionic current across an array of solid-state nanopores, requiring no additional fabrication steps. Proof-of-principle experiments are conducted that show simultaneous optical detection and characterization of ssDNA and dsDNA using an array of pores. Through a comparison with electrical measurements, we show that optical measurements are capable of accessing equivalent transmembrane current information

CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes

Binding of sweet, umami, and bitter tastants to G protein-coupled receptors (GPCRs) in apical membranes of type II taste bud cells (TBCs) triggers action potentials that activate a voltage-gated nonselective ion channel to release ATP to gustatory nerves mediating taste perception. Although calcium homeostasis modulator 1 (CALHM1) is necessary for ATP release, the molecular identification of the channel complex that provides the conductive ATP-release mechanism suitable for action potential-dependent neurotransmission remains to be determined. Here we show that CALHM3 interacts with CALHM1 as a pore-forming subunit in a CALHM1/CALHM3 hexameric channel, endowing it with fast voltage-activated gating identical to that of the ATP-release channel in vivo. Calhm3 is co-expressed with Calhm1 exclusively in type II TBCs, and its genetic deletion abolishes taste-evoked ATP release from taste buds and GPCR-mediated taste perception. Thus, CALHM3, together with CALHM1, is essential to form the fast voltage-gated ATP-release channel in type II TBCs required for GPCR-mediated tastes. Ma et al. identify a CALHM1/CALHM3 hetero-hexameric ion channel as the mechanism by which type II taste bud cells release ATP as a neurotransmitter to gustatory neurons in response to GPCR-mediated tastes, including sweet, bitter, and umami substances. © 2018 Elsevier Inc