Exploring the feasibility of Conjoint Analysis as a tool for prioritizing innovations for implementation

Background: In an era of scarce and competing priorities for implementation, choosing what to implement is a key decision point for many behavioural change projects. The values and attitudes of the professionals and managers involved inevitably impact the priority attached to decision options. Reliably capturing such values is challenging. Methods: This paper presents an approach for capturing and incorporating professional values into the prioritization of healthcare innovations being considered for adoption. Conjoint Analysis (CA) was used in a single UK Primary Care Trust to measure the priorities of healthcare professionals working with women with postnatal depression. Rating-based CA data was gathered using a questionnaire and then mapped onto 12 interventions being considered as a means of improving the management of postnatal depression. Results: The ‘impact on patient care’ and the ‘quality of supporting evidence’ associated with the potential innovations were the most influential in shaping priorities. Professionals were least influenced by whether an innovation was an existing national or local priority, or whether current practice in the Trust was meeting minimum standards. Ranking the 12 innovations by the preferences of potential adopters revealed ‘guided self help’ was the top priority for implementation and ‘screening questions for post natal depression’ the least. When other factors were considered (such as the presence of routine data or planned implementation activity elsewhere in the Trust), the project team chose to combine the eight related treatments and implement these as a single innovation referred to as ‘psychological therapies’. Conclusions: Using Conjoint Analysis to prioritise potential innovation implementation options is a feasible means of capturing the utility of stakeholders and thus increasing the chances of an innovation being adopted. There are some practical barriers to overcome such as increasing response rates to conjoint surveys before routine and unevaluated use of this technique should be considered

Embryology and bony malformations of the craniovertebral junction

BACKGROUND: The embryology of the bony craniovertebral junction (CVJ) is reviewed with the purpose of explaining the genesis and unusual configurations of the numerous congenital malformations in this region. Functionally, the bony CVJ can be divided into a central pillar consisting of the basiocciput and dental pivot and a two-tiered ring revolving round the central pivot, comprising the foramen magnum rim and occipital condyles above and the atlantal ring below. Embryologically, the central pillar and the surrounding rings descend from different primordia, and accordingly, developmental anomalies at the CVJ can also be segregated into those affecting the central pillar and those affecting the surrounding rings, respectively. DISCUSSION: A logical classification of this seemingly unwieldy group of malformations is thus possible based on their ontogenetic lineage, morbid anatomy, and clinical relevance. Representative examples of the main constituents of this classification scheme are given, and their surgical treatments are selectively discussed

Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1) TAg mice offspring

<p>Abstract</p> <p>Background</p> <p>Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring.</p> <p>Methods</p> <p>Female SV 129 mice were divided into two groups and placed on diets containing either 10% w/w corn oil (which is 50% n-6 PUFA, control diet) or 10% w/w canola oil (which is 20% n-6 PUFA, 10% n-3 PUFA, test diet). After two weeks on the diets the females were bred with homozygous C3(1) TAg transgenic mice. Mother mice consumed the assigned diet throughout gestation and nursing of the offspring. After weaning, all female offspring were maintained on the control diet.</p> <p>Results</p> <p>Compared to offspring of mothers fed the corn oil diet (CO/CO group), offspring of mothers fed the canola oil diet (CA/CO group) had significantly fewer mammary glands with tumors throughout the experiment. At 130 days of age, the CA/CO group had significantly fewer tumors per mouse (multiplicity); the tumor incidence (fraction of mice with any tumor) and the total tumor weight (per mouse that developed tumor) was less than one half that of the CO/CO group. At 170 days of age, the total tumor weight per mouse was significantly less in the CA/CO group and if a tumor developed the rate of tumor growth rate was half that of CO/CO group. These results indicate that maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed growth of the tumors that developed.</p> <p>Conclusions</p> <p>Substituting canola oil for corn oil is an easy dietary change for people to make; such a change to the maternal diet may decrease risk for breast cancer in the daughter.</p

Evidence of Key Tinnitus-Related Brain Regions Documented by a Unique Combination of Manganese-Enhanced MRI and Acoustic Startle Reflex Testing

Animal models continue to improve our understanding of tinnitus pathogenesis and aid in development of new treatments. However, there are no diagnostic biomarkers for tinnitus-related pathophysiology for use in awake, freely moving animals. To address this disparity, two complementary methods were combined to examine reliable tinnitus models (rats repeatedly administered salicylate or exposed to a single noise event): inhibition of acoustic startle and manganese-enhanced MRI. Salicylate-induced tinnitus resulted in wide spread supernormal manganese uptake compared to noise-induced tinnitus. Neither model demonstrated significant differences in the auditory cortex. Only in the dorsal cortex of the inferior colliculus (DCIC) did both models exhibit supernormal uptake. Therefore, abnormal membrane depolarization in the DCIC appears to be important in tinnitus-mediated activity. Our results provide the foundation for future studies correlating the severity and longevity of tinnitus with hearing loss and neuronal activity in specific brain regions and tools for evaluating treatment efficacy across paradigms

The granite‑hosted Variscan gold deposit from Santo António mine in the Iberian Massif (Penedono, NW Portugal): constraints from mineral chemistry, fuid inclusions, sulfur and noble gases isotopes

The study area is located in the Central Iberian Zone, a major tectonic unit of the Iberian Massif (Variscan belt). In this region the basement is composed of Cambrian-Ordovician sedimentary and minor volcanic rocks that underwent deformation and metamorphism during the Carboniferous. These metamorphic rocks host ca. 331–308 Ma granitic plutons emplaced during the D2 extensional and D3–D4 contractional deformation phases. The gold-bearing quartz veins from the Santo António mine (Penedono region) occur in granite formed at 310.1 ± 1.1 Ma and post-dated the peak of metamorphism. Gold–silver alloy is included in quartz, but mainly occurs in spaces between grains or micro-fractures within arsenopyrite of all three generations and less in pyrite. Late sulphides and sulphosalts were deposited along fractures mainly in arsenopyrite, and locally surrounding the gold–silver alloy grains. Ferberite, scheelite and stolzite replace arsenopyrite. The abundant aqueous carbonic fluids and the occurrence of a low-salinity fluid and their minimum possible entrapment temperature of 360–380 °C suggest that this gold-forming event began during the waning stages of the Variscan orogeny. The mean δ34S values of arsenopyrite and pyrite are − 4.7‰ and − 3.8‰, respectively. He–Ar–Ne isotopic data suggest a crustal origin. The ascent of the granite magma has provided the heat for remobilization of gold, other metals and metalloids from the metamorphic rocks. This gold-arsenopyrite deposit has thus similar characteristics as other selected gold-arsenopyrite deposits from the Iberian Massif, but it contains tungstates.El área de estudio está ubicada en la Zona Centroibérica, una importante unidad tectónica del Macizo Ibérico (cinturón varisco). En esta región el basamento está compuesto por rocas sedimentarias y volcánicas del Cámbrico-Ordovícico tectonizadas y metamorfzadas durante el Carbonífero. Estas rocas metamórfcas sirven como caja de los plutones graníticos datados en torno a 331–308 Ma y que fueron emplazados durante la fase de deformación extensional D2 y las fases de deformación contraccional D3 y D4. Las venas de cuarzo ricas en oro de la mina de Santo António (región de Penedono) que aparecen en un granito datado a los 310.1 ± 1.1 Ma son posteriores al pico metamórfco regional. La aleación de oro y plata se incluye en el cuarzo, pero se produce principalmente en los espacios entre granos o micro-fracturas dentro de arsenopirita de las tres generaciones y menos en pirita. Los sulfuros y sulfuros tardíos se depositaron a lo largo de las fracturas principalmente en arsenopirita, y alrededor de los granos de aleación de oro y plata. Ferberita, scheelita y la estolzita sustituyen a la arsenopirita. Los abundantes líquidos acuosos carbónicos y la presencia de un fuido de baja salinidad y su posible temperatura de atrapamiento mínima en torno de 360-380 ºC sugieren que este evento de formación de oro comenzó durante las etapas fnales de la orogenia varisca. Los valores medios de S de arsenopirita y pirita son − 4.7 ‰ y − 3.8 ‰, respectivamente. Los datos isotópicos de He–Ar–Ne sugieren que en el origen de los fuidos mineralizados participa la corteza continental. El ascenso del magma granítico ha provisto el calor para la movilización del oro, otros metales y metaloides desde las rocas metamórfcas. Este depósito de oroarsenopirita tiene así características similares a otros yaciamientos con arsenopirita y oro del Macizo Ibérico, pero sin embargo contienen tungstates.This research was financially supported by Fundação para a Ciência e Tecnologia through the projects GOLDGranites, Orogenesis, Long-term strain/stress and Deposition of ore metals—PTDC/GEO-GEO/2446/2012: COMPETE: FCOMP-01-0124-FEDER-029192 and UID/GEO/04035/2013

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference