1,434 research outputs found
Collective intellectual property rights for the development of creative tourist districts: an exploration
In this paper the institution of Collective Intellectual Property Rights (CIPR) is proposed as a regulatory tool for the development of Creative Tourist Districts based on local knowledge and trust, described as a superior organisational model of destinations to alternative models founded on individual property. As there are various types and contexts of applications of CIPR, as well as different development objectives to be achieved, the paper designs a strategy to maximise the expected impacts from case to case. It then proposes “area labels”, based on a combination of controls on quality and delimitation of areas of validity of the right, as the best instrument to foster a strategic orientation to quality across the local tourism industry.
Looking for a new panacea in ALK-rearranged NSCLC: may be Ceritinib?
In the past decade, the advent of targeted therapy led to a silent revolution
in the war against lung cancer and a significant evolution on the concept
of Phase I clinical trials design. Thanks to the specificity of their target,
the new drugs have radically changed NSCLC treatment, leading to the development
of personalized strategies. The accelerated approval of the first
ALK-inhibitor, Crizotinib and more recently Ceritinib, without a Phase III
randomized, clinical trial, has been an amazing success story in lung cancer
research, marking the beginning of a new decade of targeted drugs development,
characterized by modern, biomarker-driven, early clinical trial design
and shorter times for clinical approval. Is Ceritinib a new panacea for the
treatment of ALK-rearranged NSCLC? We aimed to discuss the reasons of
such success, including the new emerging questions, regarding mechanisms
of acquired resistance, and the best treatment algorithm for ALK-rearranged
NSCLC patients
Sterol profiles in plasma and erythrocyte membranes in patients with Smith-Lemli-Opitz syndrome: a six-year experience
Background: This study reports our experience over the last
six years in the diagnosis of Smith-Lemli-Opitz syndrome
and other inborn errors of cholesterol biosynthesis.
Methods: Gas chromatography/mass spectrometry was used
to obtain sterol profiles in plasma and erythrocyte membranes
of suspected patients.
Results: Plasma sterol reference values calculated in unaffected
subjects (ns276) were in agreement with those previously
reported. Among patients investigated from 2005 to
2010, we report 16 patients affected by Smith-Lemli-Opitz
syndrome, three of whom represent new cases and 13 of
whom were follow-up patients. In this period we also identified
a new case of chondrodysplasia punctata 2 X-linked.
The estimated incidence obtained for Smith-Lemli-Opitz
syndrome was 1:93 suspected patients (1.08%). We also
studied the effect of storage on the dehydrocholesterols/
cholesterol ratio in plasma and erythrocyte membranes of
patients affected by Smith-Lemli-Opitz syndrome stored at
–208C for up to 22 and 20 months, respectively. A significant
negative linear correlation between storage time and the
dehydrocholesterols/cholesterol ratio was identified in both
plasma and erythrocyte membranes. The decrease in the
dehydrocholesterols/cholesterol ratio in erythrocyte membranes
was at least two-fold higher than in plasma.
Conclusions: The results of this study may be helpful for
diagnosis and interpretation of data in patients with findings
suggestive of a cholesterol biosynthesis defect
Patterns of genomic instability in gastric cancer: clinical implications and perspectives.
In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to the transcriptional silencing of various genes in gastric carcinogenesis. Intriguingly, more recently in addition to CpG island hypermethylation, a global DNA demethylation, that precedes genomic damage, has been observed in GC. Thus, epigenetic alterations may play a relevant role in gastric carcinogenesis as alternative mechanisms. Evidence suggests that although MSI, CIN and CIMP phenotypes can be distinguished from one another, there might be some degree of overlap. This review describes our current knowledge of the instability pathways in gastric carcinogenesis and the potential clinical applications for different forms of genomic instability in GC
A Finite-Volume Method for Fluctuating Dynamical Density Functional Theory
We introduce a finite-volume numerical scheme for solving stochastic
gradient-flow equations. Such equations are of crucial importance within the
framework of fluctuating hydrodynamics and dynamic density functional theory.
Our proposed scheme deals with general free-energy functionals, including, for
instance, external fields or interaction potentials. This allows us to simulate
a range of physical phenomena where thermal fluctuations play a crucial role,
such as nucleation and other energy-barrier crossing transitions. A
positivity-preserving algorithm for the density is derived based on a hybrid
space discretization of the deterministic and the stochastic terms and
different implicit and explicit time integrators. We show through numerous
applications that not only our scheme is able to accurately reproduce the
statistical properties (structure factor and correlations) of the physical
system, but, because of the multiplicative noise, it allows us to simulate
energy barrier crossing dynamics, which cannot be captured by mean-field
approaches
Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study
Introduction: The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease. Material and methods: Temozolomide was administered orally at 150 mg/mq/day for five consecutive days for the first cycle, doses were increased to 200 mg/mq/day for 5 days every 28 days for subsequent cycles if no grade 3/4 haematological toxicity was observed. Eligibility criteria included cytological or histological confirmed NSCLC; BrM, recurrent or progressing after WBRT and at least one line of chemotherapy. A total of 30 consecutive patients entered the study and received the allocated treatment. Results: Three patients (10%) achieved an objective response (OR) of BrM with two complete remission. Stable disease and progressive disease were achieved in 3 (10%) and 24 patients (80%), respectively. A correlation between response to TMZ and sensitivity to the previous first line chemotherapy was reported. Time to progression and overall survival were examined both for responder patients and for all included patients. For long-term survivors, we considered the patients who survived >12 months after the start of TMZ. According to this definition, three patients resulted long-term survivors: 2 with OR and 1 with stable brain disease. No grades 3 or 4 toxicity occurred. The total of treatment-related adverse events were mild or moderate (G1-2) in intensity. No patients discontinued TMZ as a result of treatment-related toxicity. Discussion: The results of the present trial clearly demonstrates that TMZ is active and safe in BrM NSCLC patients previously treated with WBRT and at least one line of chemotherapy. © 2005 Elsevier Ireland Ltd. All rights reserved
Germline copy number variation in the YTHDC2 gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?
Objective: The vast majority of pancreatic cancers occurs sporadically. The
discovery of frequent variations in germline gene copy number can significantly
influence the expression levels of genes that predispose to pancreatic
adenocarcinoma. We prospectively investigated whether patients with
sporadic pancreatic adenocarcinoma share specific gene copy number
variations (CNVs) in their germline DNA.
Patients and methods: DNA samples were analyzed from peripheral
leukocytes from 72 patients with a diagnosis of sporadic pancreatic adenocarcinoma
and from 60 controls using Affymetrix 500K array set. Multiplex
ligation-dependent probe amplification (MLPA) assay was performed using
a set of self-designed MLPA probes specific for seven target sequences.
Results: We identified a CNV-containing DNA region associated with pancreatic
cancer risk. This region shows a deletion of 1 allele in 36 of the 72 analyzed
patients but in none of the controls. This region is of particular interest since it
contains the YTHDC2 gene encoding for a putative DNA/RNA helicase, such
protein being frequently involved in cancer susceptibility. Interestingly,
82.6% of Sicilian patients showed germline loss of one allele.
Conclusions: Our results suggest that the YTHDC2 gene could be a potential
candidate for pancreatic cancer susceptibility and a useful marker for early
detection as well as for the development of possible new therapeutic strategies
Analysis of Germline Gene Copy Number Variants of Patients with Sporadic Pancreatic Adenocarcinoma Reveals Specific Variations
Objectives: The rapid fatality of pancreatic cancer is, in large
part, the result of diagnosis at an advanced stage in the majority
of patients. Identification of individuals at risk of developing
pancreatic adenocarcinoma would be useful to improve
the prognosis of this disease. There is presently no
biological or genetic indicator allowing the detection of patients
at risk. Our main goal was to identify copy number
variants (CNVs) common to all patients with sporadic pancreatic
cancer. Methods: We analyzed gene CNVs in leukocyte
DNA from 31 patients with sporadic pancreatic adenocarcinoma
and from 93 matched controls. Genotyping was
performed with the use of the GeneChip Human Mapping
500K Array Set (Affymetrix). Results: We identified 431 single
nucleotide polymorphism (SNP) probes with abnormal hy-bridization signal present in the DNA of all 31 patients. Of
these SNP probes, 284 corresponded to 3 or more copies and
147 corresponded to 1 or 0 copies. Several cancer-associated
genes were amplified in all patients. Conversely, several
genes supposed to oppose cancer development were present
as single copy. Conclusions: These data suggest that a
set of 431 CNVs could be associated with the disease. This set
could be useful for early diagnosis
Evolution of the medical education policy in Cabo Verde
Cabo Verde is one of the world’s Small Island Developing States, with its own specificities and challenges. Independent 43 years ago, with half a million inhabitants, the education of its physicians has been done abroad, increasing the country’s workforce but not enough in number and differentiation to support the challenges of health care, namely the extension of universal coverage. In 2015 the authorities decided to implement local medical education, making it necessary to reformulate the Medical Education Policy as an education and health policy involving the many actors, organizations, and institutions. The objective of this article is to analyze the perception of several key informants of the Cabo Verdean society about the medical education in the country and to propose means to reformulate its Policy of Medical Education. A qualitative study that results from the content analysis of interviews and group discussions, as well as news in the Cabo Verdean media, identified key elements of policy reformulation in terms of content, context, processes and main actors involved in the reconsideration of the medical course. Respondents considered essential to have an engaging medical education policy to guide the development of the course and identifies the key drivers for its implementation. Cabo Verde é um dos Pequenos Estados Insulares em Desenvolvimento do mundo, com especificidades e desafios próprios. Independente há 43 anos, com meio milhão de habitantes, a formação dos seus médicos tem sido feita no exterior, incrementando a força de trabalho do país, mas não o suficiente, em número e diferenciação, para sustentar os desafios da saúde, nomeadamente a extensão da cobertura universal. Em 2015 as autoridades decidiram implantar a educação médica local, tornando necessário reformular a Política de Educação Médica enquanto política de educação e de saúde, envolvendo os vários atores, organizações e instituições. O objetivo deste artigo é analisar a percepção de vários informantes-chave sobre a implantação da educação médica em Cabo Verde e propor subsídios à reformulação da sua Política de Educação Médica. Um estudo qualitativo que resulta da análise de conteúdo de entrevistas e discussões em grupo, bem como de notícias na media cabo-verdiana, identificou elementoschave da reformulação de políticas em termos de conteúdo, contexto, processos e principais atores envolvidos na reconsideração do curso de medicina. Os entrevistados consideraram essencial ter uma política de educação médica envolvente que oriente o desenvolvimento do curso e identifique os principais impulsionadores de sua implementação.publishersversionpublishe
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