The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

An integrated silicon sensor with microfluidic chip for monitoring potassium and pH

We present ion-sensitive field effect transistor-based sensors, integrated with a microfluidic chip, for monitoring pH and potassium cations. The sensor is strategically located at the base of a well so that the response time of the device depends both on the mean flow through the device and the diffusion coefficient of the analyte being monitored. This would enable monitoring of ions in the presence of larger molecules. The dependence of the device response time on diffusive transport of analytes was examined through a numerical study of the flow field and the passive diffusion of a chemical species. The predicted device response time was compared with the experimental measurements and reasonable agreement found. The general dependence of device response time on geometry, flow rate, and analyte diffusion coefficient was derived. These devices can be used with biological fluids where monitoring of pH and cations provide vital information about the well-being of patients. © 2010 Springer-Verlag

Phosphorylation and Ubiquitination Regulate Protein Phosphatase 5 Activity and Its Prosurvival Role in Kidney Cancer

The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity. Here, we show an “on/off switch” mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90. Overexpression of the phosphomimetic T362E-PP5 mutant hyper-dephosphorylates substrates such as the co-chaperone Cdc37 and glucocorticoid receptor in cells. Our proteomic approach revealed that the tumor suppressor von Hippel-Lindau protein (VHL) interacts with and ubiquitinates K185/K199-PP5 for proteasomal degradation in a hypoxia- and prolyl-hydroxylation-independent manner. Finally, VHL-deficient clear cell renal cell carcinoma (ccRCC) cell lines and patient tumors exhibit elevated PP5 levels. Downregulation of PP5 causes ccRCC cells to undergo apoptosis, suggesting a prosurvival role for PP5 in kidney cancer

Apoptosis assays with lymphoma cell lines: problems and pitfalls

Much attention has been focused on the manner in which tumour cells die after treatment with cytotoxic agents. The basic question is whether cells die via apoptosis or via direct damage from the toxic agent. Various assays have been used to make this distinction. However, we show herein that some of the widely used assays for apoptosis do not in fact distinguish between apoptosis and other forms of cell death. More specifically: (1) A sub-G1 DNA content, identified by propidium iodide staining, does not distinguish between apoptotic and necrotic cells; (2) loss of mitochondrial membrane potential does not distinguish between apoptotic and necrotic cells, unless combined with an assay for an intact cell membrane; (3) subcellular fragments that arise from dead cells or from apoptotic bodies can interfere with some assays for apoptosis such as annexin V staining, as they may be close to the size of intact cells, making it difficult to decide where to set the size threshold; (4) irradiated cells display a large increase in nonspecific Ab binding. This may be partly due to an increase in cell size, but, regardless of the cause, it can lead to a mistaken conclusion that there is an increase in a particular antigen if appropriate control reagents are not tested; and (5) experiments utilising Ab crosslinking have neglected the role of cell aggregation, which can cause multiple problems including death from mechanical stress when cells are handled. Consideration of these factors will improve our ability to determine the mode of cell death

Neuropeptide Receptor Transcriptome Reveals Unidentified Neuroendocrine Pathways

Neuropeptides are an important class of molecules involved in diverse aspects of metazoan development and homeostasis. Insects are ideal model systems to investigate neuropeptide functions, and the major focus of insect neuropeptide research in the last decade has been on the identification of their receptors. Despite these vigorous efforts, receptors for some key neuropeptides in insect development such as prothoracicotropic hormone, eclosion hormone and allatotropin (AT), remain undefined. In this paper, we report the comprehensive cloning of neuropeptide G protein-coupled receptors from the silkworm, Bombyx mori, and systematic analyses of their expression. Based on the expression patterns of orphan receptors, we identified the long-sought receptor for AT, which is thought to stimulate juvenile hormone biosynthesis in the corpora allata (CA). Surprisingly, however, the AT receptor was not highly expressed in the CA, but instead was predominantly transcribed in the corpora cardiaca (CC), an organ adjacent to the CA. Indeed, by using a reverse-physiological approach, we purified and characterized novel allatoregulatory peptides produced in AT receptor-expressing CC cells, which may indirectly mediate AT activity on the CA. All of the above findings confirm the effectiveness of a systematic analysis of the receptor transcriptome, not only in characterizing orphan receptors, but also in identifying novel players and hidden mechanisms in important biological processes. This work illustrates how using a combinatorial approach employing bioinformatic, molecular, biochemical and physiological methods can help solve recalcitrant problems in neuropeptide research

Expressed sequence tags from Atta laevigata and identification of candidate genes for the control of pest leaf-cutting ants

<p>Abstract</p> <p>Background</p> <p>Leafcutters are the highest evolved within Neotropical ants in the tribe Attini and model systems for studying caste formation, labor division and symbiosis with microorganisms. Some species of leafcutters are agricultural pests controlled by chemicals which affect other animals and accumulate in the environment. Aiming to provide genetic basis for the study of leafcutters and for the development of more specific and environmentally friendly methods for the control of pest leafcutters, we generated expressed sequence tag data from <it>Atta laevigata</it>, one of the pest ants with broad geographic distribution in South America.</p> <p>Results</p> <p>The analysis of the expressed sequence tags allowed us to characterize 2,006 unique sequences in <it>Atta laevigata</it>. Sixteen of these genes had a high number of transcripts and are likely positively selected for high level of gene expression, being responsible for three basic biological functions: energy conservation through redox reactions in mitochondria; cytoskeleton and muscle structuring; regulation of gene expression and metabolism. Based on leafcutters lifestyle and reports of genes involved in key processes of other social insects, we identified 146 sequences potential targets for controlling pest leafcutters. The targets are responsible for antixenobiosis, development and longevity, immunity, resistance to pathogens, pheromone function, cell signaling, behavior, polysaccharide metabolism and arginine kynase activity.</p> <p>Conclusion</p> <p>The generation and analysis of expressed sequence tags from <it>Atta laevigata </it>have provided important genetic basis for future studies on the biology of leaf-cutting ants and may contribute to the development of a more specific and environmentally friendly method for the control of agricultural pest leafcutters.</p

Key mechanisms governing resolution of lung inflammation

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered

The Inherent Complexity of Computer Use among End-Users: Implications for Research and Practice

We argue that sub-optimal computer use persists among end-users, which may be partly explained by the fact that computer use is inherently complex. We cull from assorted literatures two definitional criteria of complexity--numerousness and heterogeneity, which we offer as theoretical justification for why computer use is appropriately characterized as complex. We build from this theoretical justification by drawing parallel arguments on the constitutive properties of language and computer literacy. We suggest that a theoretical elaboration of computer use as presented here may offer benefit to research for conceptualizing and measuring computer literacy, and to practice for informing training program design options