Knowledge mobilization in the context of health technology assessment: an exploratory case study

<p>Abstract</p> <p>Background</p> <p>Finding measures to enhance the dissemination and implementation of their recommendations has become part of most health technology assessment (HTA) bodies' preoccupations. The Quebec government HTA organization in Canada observed that some of its projects relied on innovative practices in knowledge production and dissemination. A research was commissioned in order to identify what characterized these practices and to establish whether they could be systematized.</p> <p>Methods</p> <p>An exploratory case study was conducted during summer and fall 2010 in the HTA agency in order to determine what made the specificity of its context, and to conceptualize an approach to knowledge production and dissemination that was adapted to the mandate and nature of this form of HTA organization. Six projects were selected. For each, the HTA report and complementary documents were analyzed, and semi-structured interviews were carried out. A narrative literature review of the most recent literature reviews of the principal knowledge into practice frameworks (2005-2010) and of articles describing such frameworks (2000-2010) was undertaken.</p> <p>Results and discussion</p> <p>Our observations highlighted an inherent difficulty as regards applying the dominant knowledge translation models to HTA and clinical guidance practices. For the latter, the whole process starts with an evaluation question asked in a problematic situation for which an actionable answer is expected. The objective is to produce the evidence necessary to respond to the decision-maker's request. The practices we have analyzed revealed an approach to knowledge production and dissemination, which was multidimensional, organic, multidirectional, dynamic, and dependent on interactions with stakeholders. Thus, HTA could be considered as a knowledge mobilization process per se.</p> <p>Conclusions</p> <p>HTA's purpose is to solve a problem by mobilizing the types of evidence required and the concerned actors, in order to support political, organizational or clinical decision-making. HTA relies on the mediation between contextual, colloquial and scientific evidence, as well as on interactions with stakeholders for recommendation making. Defining HTA as a knowledge mobilization process might contribute to consider the different orders of knowledge, the social, political and ethical dimensions, and the interactions with stakeholders, among the essential components required to respond to the preoccupations, needs and contexts of all actors concerned with the evaluation question's issues.</p

Islands beneath islands: phylogeography of a groundwater amphipod crustacean in the Balearic archipelago

<p>Abstract</p> <p>Background</p> <p>Metacrangonyctidae (Amphipoda, Crustacea) is an enigmatic continental subterranean water family of marine origin (thalassoid). One of the species in the genus, <it>Metacrangonyx longipes</it>, is endemic to the Balearic islands of Mallorca and Menorca (W Mediterranean). It has been suggested that the origin and distribution of thalassoid crustaceans could be explained by one of two alternative hypotheses: (1) active colonization of inland freshwater aquifers by a marine ancestor, followed by an adaptative shift; or (2) passive colonization by stranding of ancestral marine populations in coastal aquifers during marine regressions. A comparison of phylogenies, phylogeographic patterns and age estimations of clades should discriminate in favour of one of these two proposals.</p> <p>Results</p> <p>Phylogenetic relationships within <it>M. longipes </it>based on three mitochondrial DNA (mtDNA) and one nuclear marker revealed five genetically divergent and geographically structured clades. Analyses of cytochrome oxidase subunit 1 (<it>cox1</it>) mtDNA data showed the occurrence of a high geographic population subdivision in both islands, with current gene flow occurring exclusively between sites located in close proximity. Molecular-clock estimations dated the origin of <it>M. longipes </it>previous to about 6 Ma, whereas major cladogenetic events within the species took place between 4.2 and 2.0 Ma.</p> <p>Conclusions</p> <p><it>M. longipes </it>displayed a surprisingly old and highly fragmented population structure, with major episodes of cladogenesis within the species roughly correlating with some of the major marine transgression-regression episodes that affected the region during the last 6 Ma. Eustatic changes (vicariant events) -not active range expansion of marine littoral ancestors colonizing desalinated habitats-explain the phylogeographic pattern observed in <it>M. longipes</it>.</p

Alterations in gene expression profiles correlated with cisplatin cytotoxicity in the glioma U343 cell line

Gliomas are the most common tumors in the central nervous system, the average survival time of patients with glioblastoma multiforme being about 1 year from diagnosis, in spite of harsh therapy. Aiming to study the transcriptional profiles displayed by glioma cells undergoing cisplatin treatment, gene expression analysis was performed by the cDNA microarray method. Cell survival and apoptosis induction following treatment were also evaluated. Drug concentrations of 12.5 to 300 μM caused a pronounced reduction in cell survival rates five days after treatment, whereas concentrations higher than 25 μM were effective in reducing the survival rates to ~1%. However, the maximum apoptosis frequency was 20.4% for 25 μM cisplatin in cells analyzed at 72 h, indicating that apoptosis is not the only kind of cell death induced by cisplatin. An analysis of gene expression revealed 67 significantly (FDR < 0.05) modulated genes: 29 of which down- and 38 up-regulated. These genes belong to several classes (metabolism, protein localization, cell proliferation, apoptosis, adhesion, stress response, cell cycle and DNA repair) that may represent several affected cell processes under the influence of cisplatin treatment. The expression pattern of three genes (RHOA, LIMK2 and TIMP2) was confirmed by the real time PCR method

It's not too Late for the Harpy Eagle (Harpia harpyja): High Levels Of Genetic Diversity and Differentiation Can Fuel Conservation Programs

Article on the harpy eagle (Harpia harpyja) and how high levels of genetic diversity and differentiation can fuel conservation programs

Lineage diversification and historical demography of a montane bird Garrulax elliotii - implications for the Pleistocene evolutionary history of the eastern Himalayas

<p>Abstract</p> <p>Background</p> <p>Pleistocene climate fluctuations have shaped the patterns of genetic diversity observed in many extant species. In montane habitats, species' ranges may have expanded and contracted along an altitudinal gradient in response to environmental fluctuations leading to alternating periods of genetic isolation and connectivity. Because species' responses to climate change are influenced by interactions between species-specific characteristics and local topography, diversification pattern differs between species and locations. The eastern Himalayas is one of the world's most prominent mountain ranges. Its complex topography and environmental heterogeneity present an ideal system in which to study how climatic changes during Pleistocene have influenced species distributions, genetic diversification, and demography. The Elliot's laughing thrush (<it>Garrulax elliotii</it>) is largely restricted to high-elevation shrublands in eastern Himalayas. We used mitochondrial DNA and microsatellites to investigate how genetic diversity in this species was affected by Pleistocene glaciations.</p> <p>Results</p> <p>Mitochondrial data detected two partially sympatric north-eastern and southern lineages. Microsatellite data, however, identified three distinct lineages congruent with the geographically separated southern, northern and eastern eco-subregions of the eastern Himalayas. Geographic breaks occur in steep mountains and deep valleys of the Kangding-Muli-Baoxin Divide. Divergence time estimates and coalescent simulations indicate that lineage diversification occurred on two different geographic and temporal scales; recent divergence, associated with geographic isolation into individual subregions, and historical divergence, associated with displacement into multiple refugia. Despite long-term isolation, genetic admixture among these subregional populations was observed, indicating historic periods of connectivity. The demographic history of <it>Garrulax elliotii </it>shows continuous population growth since late Pleistocene (about 0.125 mya).</p> <p>Conclusion</p> <p>While altitude-associated isolation is typical of many species in other montane regions, our results suggest that eco-subregions in the eastern Himalayas exhibiting island-like characteristics appear to have determined the diversification of <it>Garrulax elliotii</it>. During the Pleistocene, these populations became isolated on subregions during interglacial periods but were connected when these expanded to low altitude during cooler periods. The resultant genetic admixture of lineages might obscure pattern of genetic variation. Our results provide new insights into sky island diversification in a previously unstudied region, and further demonstrate that Pleistocene climatic changes can have profound effects on lineage diversification and demography in montane species.</p

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances