The Medicalization of Sleeplessness: A Public Health Concern

Sleeplessness, a universal condition with diverse causes, may be increasingly diagnosed and treated (or medicalized) as insomnia. We examined the trend in sleeplessness complaints, diagnoses, and prescriptions of sedative hypnotics in physician office visits from 1993 to 2007. Consistent with the medicalization hypothesis, sleeplessness complaints and insomnia diagnoses increased over time and were far outpaced by prescriptions for sedative hypnotics. Insomnia may be a public health concern, but potential overtreatment with marginally effective, expensive medications with nontrivial side effects raises definite population health concerns

Research to Practice: Self-Determination and Struggle in the Lives of Adolescents

As students of all ability levels move into adulthood, they seek to define themselves and develop goals for the future. This study identifies four categories of students and offering targeted suggestions for support

Subcellular localization of the FLT3-ITD oncogene plays a significant role in the production of NOX- and p22phox-derived reactive oxygen species in acute myeloid leukemia

Internal tandem duplication of the juxtamembrane domain of FMS-like tyrosine kinase 3 (FLT3-ITD) receptor is the most prevalent FLT3 mutation accounting for 20% of acute myeloid leukemia (AML) patients. FLT3-ITD mutation results in ligand-independent constitutive activation of the receptor at the plasma membrane and ‘impaired trafficking’ of the receptor in compartments of the endomembrane system, such as the endoplasmic reticulum (ER). FLT3-ITD expressing cells have been shown to generate increased levels of reactive oxygen species (ROS), in particular NADPH oxidase (NOX)-generated ROS which act as pro-survival signals. The purpose of this study is to investigate FLT3-ITD production of ROS at the plasma membrane and ER in the FLT3-ITD expressing AML cell line MV4-11. Receptor trafficking inhibitors; Tunicamycin and Brefeldin A induce ER retention of FLT3-ITD, resulting in a decrease in protein expression of NOX4 and its partner protein p22phox, thus demonstrating the critical importance of FLT3-ITD localization for the generation of pro-survival ROS. NOX-generated ROS contribute to total endogenous hydrogen peroxide (H2O2) in AML as quantified by flow cytometry using the cell-permeable H2O2-probe Peroxy Orange 1 (PO1). We found that PI3K/AKT signaling only occurs when FLT3-ITD is expressed at the plasma membrane and is required for the production of NOX-generated ROS. ER retention of FLT3-ITD resulted in NOX4 deglycosylation and p22phox protein degradation

Maximising Output of Beef Within Cost Efficient, Environmentally Compatible Forage Conservation Systems.

End of Project ReportA comprehensive research programme showed the potential benefits of replacing a productive old permanent grassland pasture dominated by indigenous species with new perennial or Italian ryegrass swards, when each was managed intensively, conserved as silage and fed to beef cattle. Ancillary experiments showed how the silage systems could be modified to improve productivity. However, they also showed that under a less intensive regime, replacing this old permanent pasture by ryegrass reseeds would be difficult to justify.European Union Structural Funds (EAGGF

NOX-driven ROS formation in cell transformation of FLT3-ITD positive AML

In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation including the promotion of leukemic cell proliferation and migration, as well as DNA-damage and accumulation of mutations. Work reviewed in this article has shown the involvement of NADPH oxidase (NOX)-derived ROS downstream of oncogenic protein-tyrosine kinases in both processes, and the related pathways have been partially identified. FLT3-ITD, an important oncoprotein in a subset of AML, causes activation of AKT and subsequently stabilization of p22phox, a regulatory subunit for NOX1-4. This process is linked to ROS formation and DNA damage. Moreover, FLT3-ITD signaling through STAT5 enhances expression of NOX4, ROS formation and inactivation of the protein-tyrosine phosphatase DEP-1/PTPRJ, a negative regulator of FLT3 signaling, by reversible oxidation of its catalytic cysteine residue. Genetic inactivation of NOX4 restored DEP-1 activity and attenuated cell transformation by FLT3-ITD in vitro and in vivo. Future work is required to further explore these mechanisms and their causal involvement in leukemic cell transformation, which may result in the identification of novel candidate targets for therapy

Ranking connectivity risk for phosphorus loss along agricultural drainage ditches

peer-reviewedAgricultural drainage systems comprising both in-field pipe drains and surface ditches are typically installed to remove excess water from agricultural land. These drainage networks can provide connectivity between phosphorus (P) sources and surface waters thereby increasing the risk of P loss to rivers and streams. The objective of this study was to derive a farm-scale drainage ranking that categorises drainage ditches in terms of P loss risk based on connectivity and physic-chemical characteristics. Ten pilot farms were selected to characterise drainage networks through ground survey and, sediment and water sampling. Five drainage ditch categories were derived based on landscape setting and connectivity. Each category recorded soluble and reactive P concentrations above environmental water quality standards. To assess the risk of surface ditches as a connectivity vector between agricultural P and surface waters ditches were ranked in order of P loss risk by integrating landscape position and sediment P chemistry. Elevated sediment P with high equilibrium P concentration (EPCo) were associated with ditches connected to farm yards, and in sediment sampled at ditch outlets, suggesting P deposition over time indicative of a legacy P source. The greatest risk of P loss was attributed to ditches connecting farm yards to streams, and ditches that connected the drainage network to surface waters, or Outlets. These results rank connectivity risk for P loss along agricultural drainage ditches for farm level risk assessment to target P loss mitigation measures to the appropriate locations

Toxic optic neuropathy in the setting of docetaxel chemotherapy: a case report

Background: To describe the first reported case of toxic optic neuropathy secondary to docetaxel (Taxotere®) chemotherapy. Case presentation. A 53-year-old female presented with predominantly unilateral visual loss, but extensive bilateral visual field defects and bilateral optic nerve head swelling 2 weeks after first dose of docetaxel (Taxotere®) and trastuzumab (Herceptin®) chemotherapy for a left sided node-positive, HER2 positive breast cancer. Extensive investigation ruled out other causes of optic neuropathy. She was treated with high dose corticosteroids intravenously for 1 week then a tapering oral dose over 8 weeks. Visual field defects gradually resolved and visual acuity improved. Docetaxel chemotherapy was discontinued but targeted therapy with trastuzumab continued without further complication. Conclusion: Docetaxel can cause a toxic optic neuropathy possibly due to an ischemic or neurotoxic mechanism at the optic nerve head. With cessation of docetaxel therapy and treatment with systemic corticosteroids, visual recovery can occur without significant residual visual deficit

The Complex Pathway towards Farm-Level Sustainable Intensification: An Exploratory Network Analysis of Stakeholders’ Knowledge and Perception

peer-reviewedFarm-level sustainable intensification of agriculture (SIA) has become an important concept to ensuring food security while minimising negative externalities. However, progress towards its achievement is often constrained by the different perceptions and goals of various stakeholders that affect farm management decisions. This study examines farm-level SIA as a dynamic system with interactive components that are determined by the interests of the stakeholders involved. A systems thinking approach was used to identify and describe the pathways towards farm-level SIA across the three main pillars of sustainability. An explanatory network analysis of fuzzy cognitive maps (FCMs) that were collectively created by representative groups of farmers, farm advisors and policy makers was performed. The study shows that SIA is a complex dynamic system, affected by cognitive beliefs and particular knowledge within stakeholder groups. The study concludes that, although farm-level SIA is a complex process, common goals can be identified in collective decision making

Exact asymptotic analysis for metapopulation dynamics on correlated dynamic landscapes

We compute the mean patch occupancy for a stochastic, spatially explicit patch-occupancy metapopulation model on a dynamic, correlated landscape, using a mathematically exact perturbation expansion about a mean-field limit that applies when dispersal range is large. Stochasticity in the metapopulation and landscape dynamics gives negative contributions to patch occupancy, the former being more important at high occupancy and the latter at low occupancy. Positive landscape correlations always benefit the metapopulation, but are only significant when the correlation length is comparable to, or smaller than, the dispersal range. Our analytical results allow us to consider the importance of spatial kernels in all generality. We find that the shape of the landscape correlation function is typically unimportant, and that the variance is overwhelmingly the most important property of the colonisation kernel. However, short-range singularities in either the colonisation kernel or landscape correlations can give rise to qualitatively different behaviour