Molecular pathology - The value of an integrative approach

<p>Molecular Pathology (MP) is at the heart of modern diagnostics and translational research, but the controversy on how MP is best developed has not abated. The lack of a proper model or trained pathologists to support the diagnostic and research missions makes MP a rare commodity overall. Here we analyse the scientific and technology areas, in research and diagnostics, which are encompassed by MP of solid tumours; we highlight the broad overlap of technologies and analytical capabilities in tissue research and diagnostics; and we describe an integrated model that rationalizes technical know-how and pathology talent for both. The model is based on a single, accredited laboratory providing a single standard of high-quality for biomarker discovery, biomarker validation and molecular diagnostics.</p>

Family Focused Practice in Mental Health Care: An Integrative Review

While mental health services are increasingly encouraged to engage in family-focused practice, it is a nebulous and poorly understood term. The aim of this paper was to examine and synthesize evidence on the concept and scope of family-focused practice in adult and child and youth mental health care settings. An integrative literature review method was used. Medline, Embase, CINAHL, PsycInfo and Proquest electronic databases were systematically searched forabstracts published in English between 1994-2014. Data were extracted and constant comparative analysis conducted with 40 included articles. Family-focused practice was conceptualised variously depending on who was included in the „family‟, whether the focus was family of origin or family of procreation, and the context of practice. As a finding of the review, six core and inter-related family-focused practices were identified: family care planning andgoal-setting; liaison between families and services; instrumental, emotional and social support; assessment; psychoeducation; and a coordinated system of care between families and services. While family is a troubled concept, „family‟ as defined by its members forms a basis for practice that is oriented to providing a „whole of family‟ approach to care. In order to strengthen familymembers‟ wellbeing and improve their individual and collective outcomes, key principles and practices of family-focused practice are recommended for clinicians and policy makers across mental health settings.

Integrative analysis of chemo-transcriptomic profiles for drug-feature specific gene expression signatures

One of the major challenges in systems biology is to understand the complex responses of a biological system to external perturbations or internal signalling depending on its biological conditions. Genome-wide transcriptomic profiling of cellular systems under various chemical perturbations allows the manifestation of certain features of the chemicals through their transcriptomic expression profiles. The insights obtained may help to establish the connections between human diseases, associated genes and therapeutic drugs. The main objective of this study was to systematically analyse cellular gene expression data under various drug treatments to elucidate drug-feature specific transcriptomic signatures. We first extracted drug-related information (drug features) from the collected textual description of DrugBank entries using text-mining techniques. A novel statistical method employing orthogonal least square learning was proposed to obtain drug-feature-specific signatures by integrating gene expression with DrugBank data. To obtain robust signatures from noisy input datasets, a stringent ensemble approach was applied with the combination of three techniques: resampling, leave-one-out cross validation, and aggregation. The validation experiments showed that the proposed method has the capacity of extracting biologically meaningful drug-feature-specific gene expression signatures. It was also shown that most of signature genes are connected with common hub genes by regulatory network analysis. The common hub genes were further shown to be related to general drug metabolism by Gene Ontology analysis. Each set of genes has relatively few interactions with other sets, indicating the modular nature of each signature and its drug-feature-specificity. Based on Gene Ontology analysis, we also found that each set of drug feature (DF)-specific genes were indeed enriched in biological processes related to the drug feature. The results of these experiments demonstrated the pot- ntial of the method for predicting certain features of new drugs using their transcriptomic profiles, providing a useful methodological framework and a valuable resource for drug development and characterization.

Peacebuilding and Consociational Electoral Engineering in Bosnia-Herzegovina'

What role do elections play in societies emerging from communal war and what type of institutions can serve as catalysts in deepening peace and compromise? While some analysts argue that ethnicity should be recognized through 'consociational' institutions, others maintain that 'integrative' devices - in particular, carefully crafted electoral rules - can limit or even break down the salience of ethnicity and increase the possibility for inter-ethnic accommodation. This article examines the post-war electoral experience of Bosnia and Herzegovina (BiH), arguing that elections had a problematic, unintended impact on peacebuilding. First, timid integrative electoral devices were adopted in a consociational system that reifies ethnic division and complicates compromise; second, peacebuilding agencies needlessly manufactured electoral rules that backfired; third, group-based features of the BiH political system run counter to individual human rights. The article ends with suggestions for improving the electoral framework.

An Innovative Approach to Evaluating Organisational Change

This paper addresses the difficult problem of how to improve the process of evaluating organisational change. Given that the data emergent from an evaluative exercise will strongly influence the subsequent strategic and operational decisions taken by organisational managers, it is critical that the evaluation approach itself is capable of delivering high quality, accurate and timely data. The aim of this paper is to examine the role of the IT-based Optionfinder Technology used in conjunction with focus groups, in generating management decision-making data, and reflecting the changes in key performance indicators in a utility organisation. The case study research evaluates the innovative integrative approach adopted by the utility organisation and concludes that the proposed approach contributes to improvements in the decision-making capability of managers.

Differential energy costs of winter acclimatized common spiny mice Acomys cahirinus from two adjacent habitats

The common spiny mouse Acomys cahirinus, of Ethiopian origin, has a widespread distribution across arid, semi-arid and Mediterranean parts of the Arabian sub-region. We compared the daily energy expenditure (DEE), water turnover NTTO) and sustained metabolic scope (SusMS = DEE/resting metabolic rate) of two adjacent populations during the winter. Mice were captured from North- and South- facing slopes (NFS and SFS) of the same valley, comprising mesic and xeric habitats, respectively. Both DEE and SusMS winter values were greater in NFS than SFS mice and were significantly greater than values previously measured in the summer for these two populations in the same environments. However, WTO values were consistent with previously established values and were not significantly different from allometric predictions for desert eutherians. We suggest that physiological plasticity in energy expenditure, which exists both temporally and spatially, combined with stable WTO, perhaps reflecting a xeric ancestry, has enabled A. cahirinus to invade a wide range of habitats. (C) 2003 Elsevier Inc. All rights reserved.

The effects of season and dietary salt content on body temperature daily rhythms of common spiny mice from different micro-habitats

We compared body temperature (T-b) daily rhythms in two populations of common spiny mice, Acomys cahirinus, during summer and winter months in relation to increasing dietary salt content. Mice were collected from the North and South facing slopes (NFS and SFS) of the same valley, that are exhibiting mesic and xeric habitats, respectively. During the summer, whilst mice were offered a water source containing 0.9% NaCl, SFS individuals had T-b peak values at 24:00, whereas NFS individuals had peak values at 18:00. When the salinity of the water source was increased, from 0.9 to 2.5% and then 3.5%, the difference between maximal and minimal T-b of both populations increased. In addition, with increased salinity, the T-b daily peak of SFS mice shifted to 18:00. During the winter, the mean daily T-b values of both populations of mice were lower than during the summer. At 0.9% salinity, the NFS mice exhibited a daily T-b variation with a peak at the beginning of the night. However, we did not detect any significant variation in daily T-b in the SFS mice. At 2.5% salinity, the difference between the mean daily T-b of mice from the two slopes increased. In winter we were unable to increase the salinity to 3.5% as the animals began to lose weight rapidly. We suggest that common spiny mice that inhabit these two micro-habitats axe forming two discrete populations that respond differently to the environmental pressures prevailing in each habitat, by evolving different physiological capacities. (C) 2002 Elsevier Science Inc. All rights reserved.

Energetics and litter size variation in domestic dog Canis familiaris breeds of two sizes

We measured resting metabolic rate (RMR), daily energy expenditure (DEE) and metabolisable energy intake (MEI) in two breeds of dog during peak lactation to test whether litter size differences were a likely consequence of allometric variation in energetics. RMR of Labrador retrievers (30 kg, n = 12) and miniature Schnauzers (6 kg, n = 4) averaged 3437 and 1062 kJ/day, respectively. DEE of Labradors (n = 6) and Schnauzers (n = 4) averaged 9808 and 2619 kJ/day, respectively. MEI of Labradors (n = 12) was 22448 kJ/day and of Schnauzers (a = 7) was 5382 kJ/day. DEE of Labrador pups (2.13 kg, n = 19) was 974 kJ/day and Schnauzers (0.89 kg, n = 7) were 490 kJ/day. Although Labradors had higher MEIs than Schnauzers during peak lactation, there was no difference in mass-specific energy expenditure between the two breeds. Hence, it is unlikely that litter size variation is a likely consequence of differences in maternal energy expenditure. Individual offspring were relatively more costly for mothers of the smaller breed to produce. Therefore, litter size variations were consistent with the expectation that smaller offspring should be more costly for mothers, but not that smaller mothers should per se invest more resources in reproduction. (C) 2001 Elsevier Science Inc. All rights reserved.

Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?

Bailey DM, Taudorf S, Berg RMG, Lundby C, McEneny J, Young IS, Evans KA, James PE, Shore A, Hullin DA, McCord JM, Pedersen BK, Moller K. Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness? Am J Physiol Regul Integr Comp Physiol 297: R1283-R1292, 2009. First published September 2, 2009; doi: 10.1152/ajpregu.00366.2009.-This study examined whether hypoxia causes free radical-mediated disruption of the blood-brain barrier (BBB) and impaired cerebral oxidative metabolism and whether this has any bearing on neurological symptoms ascribed to acute mountain sickness (AMS). Ten men provided internal jugular vein and radial artery blood samples during normoxia and 9-h passive exposure to hypoxia (12.9% O-2). Cerebral blood flow was determined by the Kety-Schmidt technique with net exchange calculated by the Fick principle. AMS and headache were determined with clinically validated questionnaires. Electron paramagnetic resonance spectroscopy and ozone-based chemiluminescence were employed for direct detection of spin-trapped free radicals and nitric oxide metabolites. Neuron-specific enolase (NSE), S100 beta, and 3-nitrotyrosine (3-NT) were determined by ELISA. Hypoxia increased the arterio-jugular venous concentration difference (a-v(D)) and net cerebral output of lipid-derived alkoxyl-alkyl free radicals and lipid hydroperoxides (P