Genetic and Immune Predictors for Hypersensitivity Syndrome to Antiepileptic Drugs

Hypersensitivity syndrome reactions (HSR) to antiepileptic drugs (AED) are associated with severe clinical cutaneous adverse reactions (SCAR).Our aims are: to assess HSRs to AEDs using the in vitro lymphocyte toxicity assay (LTA) in patients who manifested HSRs clinically, to correlate LTA results with the clinical syndrome, to correlate LTA results with the human leukocyte antigen (HLA) allele B*1502 (HLA-B*1502) positivity in a Han Chinese-Canadian population, and to determine the cytokine network in this population. HSR patients developed fever and cutaneous eruptions in the presence or absence of organ involvement within 8 weeks of exposure to carbamazepine (CBZ), phenytoin (PHY) or lamotrigine (LTG). Control patients received AEDs without presenting HSR. We investigated 10 CBZ-HSR (4 presented with Stevens-Johnson syndrome (SJS)), 24 CBZ-controls, 10 PHY-HSR (4 presented with drug-induced liver injury (DILI)), 24 PHY-controls, 6 LTG-HSR (1 SJS and 1 DILI) and 24 LTG-controls. There were 30 Han Chinese individuals (14 HSR patients and 16 controls) in our cohort. LTA toxicity greater than 12.5%±2.5% was considered positive. Differences among groups were determined by analysis of variance. In addition, we measured cytokine secretion in the patient sera between 1 month and 3 years after the event. All Han Chinese individuals and 30% of Caucasians were genotyped for HLA-B*1502.A perfect correlation (r=0.92) was observed between positive LTA and clinical diagnosis of DILI and SJS/toxic epidermal necrolysis (TEN). HLA-B*1502 positivity in Han Chinese is a predictor of CBZ-HSR and PHY-HSR. HLA-B*1502-negative Han Chinese receiving only CBZ or a combination of CBZ-PHY tolerated the drug(s) clinically, presenting negative CBZ-LTA and PHY-LTA. However, 3 patients presenting negative CBZ-LTA and PHY-LTA, as well as negative HLA-B*1502, showed positive LTG-LTA (38%, 28% and 25%, respectively), implying that they should not be prescribed LTG. Three patients had LTA positive to both PHY and CBZ, and 3 others had LTA positive to both PHY and LTG. Clinically, all six patients presented HSR to both drugs that they tested positive to (cross-reactivity). Patients were grouped based on the clinical presentation of their symptoms as only rash and fever or a triad that characterizes "true" HSR (rash, fever and DILI or SJS/TEN). Levels of pro-inflammatory cytokines were significantly higher in patient sera compared to control sera. More specifically, the highest levels of tumor necrosis factor (TNF)-α was measured in patients presenting "true" HSR, as were the apoptotic markers Fas, caspase 8 activity and M30. We concluded that LTA is sensitive for DILI and SJS/TEN regardless of drug or ethnicity. HSR prediction will prevent AED-induced morbidity. In Han Chinese, HLA-B*1502 positivity is a predictor for CBZ-HSR and PHY-HSR. Its negativity does not predict a negative LTG-HSR. There is cross-reactivity between AEDs. Additionally, T-cell cytokines and chemokines control the pathogenesis of SJS/TEN and DILI, contributing to apoptotic processes in the liver and in the skin

A typology of North Sea oil and gas platforms

Acknowledgements Tis work was conducted as part of the FISHSPAMMS project, part of the INSITE programme, funded by the UK Natural Environment Research Council under grant number NE/T010681/1. We would like to thank our project partners for their input, in particular Ross Nickson and Paul Shearer, for their expertise and advice about platform characteristics.Peer reviewedPublisher PD

Using video feedback to improve early father-infant interaction: a pilot study.

Preventive interventions with parents of infants have tended to focus on mothers. Recent research focused on fathers suggests that their involvement in interventions might enhance effectiveness. One effective approach with mothers is the brief, home-based Video-feedback Intervention to promote Positive Parenting (VIPP). This paper is a report of a pilot study of VIPP with fathers to assess its feasibility. Five fathers were recruited from an existing longitudinal study of parents. The primary outcome was acceptability, assessed using a semi-structured questionnaire after completion of the intervention. All fathers completed all sessions of the intervention. Fathers rated the intervention as having had a significant impact on their understanding of their child's thoughts and feelings, and as having improved their communication and relationship with their baby. Fathers' feedback was generally positive. The flexibility to conduct sessions at home (or at fathers' places of work) and the flexible timing of sessions were identified as fundamental to successful delivery. The results of this pilot study are encouraging, as VIPP with fathers was feasible. In light of the modest sample size, and the use of a non-clinical sample, the intervention must be evaluated with larger, clinical samples to evaluate its efficacy with fathers

Modeling associations between public understanding, engagement and forest conditions in theInland Northwest, USA

Opinions about public lands and the actions of private non-industrial forest owners in the western United States play important roles in forested landscape management as both public and private forests face increasing risks from large wildfires, pests and disease. This work presents the responses from two surveys, a random-sample telephone survey of more than 1500 residents and a mail survey targeting owners of parcels with 10 or more acres of forest. These surveys were conducted in three counties (Wallowa, Union, and Baker) in northeast Oregon, USA. We analyze these survey data using structural equation models in order to assess how individual characteristics and understanding of forest management issues affect perceptions about forest conditions and risks associated with declining forest health on public lands. We test whether forest understanding is informed by background, beliefs, and experiences, and whether as an intervening variable it is associated with views about forest conditions on publicly managed forests. Individual background characteristics such as age, gender and county of residence have significant direct or indirect effects on our measurement of understanding. Controlling for background factors, we found that forest owners with higher self-assessed understanding, and more education about forest management, tend to hold more pessimistic views about forest conditions. Based on our results we argue that self-assessed understanding, interest in learning, and willingness to engage in extension activities together have leverage to affect perceptions about the risks posed by declining forest conditions on public lands, influence land owner actions, and affect support for public policies. These results also have broader implications for management of forested landscapes on public and private lands amidst changing demographics in rural communities across the Inland Northwest where migration may significantly alter the composition of forest owner goals, understanding, and support for various management actions

Modelling Associations between Public Understanding, Engagement and Forest Conditions in the Inland Northwest, USA.

Abstract Opinions about public lands and the actions of private non-industrial forest owners in the western United States play important roles in forested landscape management as both public and private forests face increasing risks from large wildfires, pests and disease. This work presents the responses from two surveys, a random-sample telephone survey of more than 1500 residents and a mail survey targeting owners of parcels with 10 or more acres of forest. These surveys were conducted in three counties (Wallowa, Union, and Baker) in northeast Oregon, USA. We analyze these survey data using structural equation models in order to assess how individual characteristics and understanding of forest management issues affect perceptions about forest conditions and risks associated with declining forest health on public lands. We test whether forest understanding is informed by background, beliefs, and experiences, and whether as an intervening variable it is associated with views about forest conditions on publicly managed forests. Individual background characteristics such as age, gender and county of residence have significant direct or indirect effects on our measurement of understanding. Controlling for background factors, we found that forest owners with higher self-assessed understanding, and more education about forest management, tend to hold more pessimistic views about forest conditions. Based on our results we argue that self-assessed understanding, interest in learning, and willingness to engage in extension activities together have leverage to affect perceptions about the risks posed by declining forest conditions on public lands, influence land owner actions, and affect support for public policies. These results also have broader implications for management of forested landscapes on public and private lands amidst changing demographics in rural communities across the Inland Northwest where migration may significantly alter the composition of forest owner goals, understanding, and support for various management actions

Oscillations and chaos in the dynamics of the BCM learning rule

The BCM learning rule originally arose from experiments intended for measuring the selectivity of neurons in the primary visual cortex, and it dependence on input stimuli. This learning rule incorporates a dynamic LTP threshold, which depends on the time averaged postsynaptic activity. Although the BCM learning rule has been well studied and some experimental evidence of neuronal adherence has been found in the other areas of the brain, including the hippocampus, there is still much to be known about the dynamic behavior of this learning rule

Forest management and wildfire risk in inland northwest

This brief reports the results of a mail survey of forest landowners in northeastern Oregon conducted in the fall of 2012 by the Communities and Forests in Oregon (CAFOR) Project at the University of Colorado and the University of New Hampshire in cooperation with Oregon State University College of Forestry Extension. The mail survey--a follow-up to a telephone survey conducted for the counties of Baker, Union, and Wallowa in the fall of 2011 -was administered to understand who constituted forest landowners in these three coun¬ties and their perceptions about forest management on both public and private land, as well as risks to forests in the area and the actions they have taken to reduce those risks. The respondents indicated that they perceive wildfire as the greatest threat to their lands, and they consider cooperation with neighbors as very or extremely important for land management. Forest landowners believe public lands are managed poorly and see a greater risk of wildfire occurring on neighboring public land than on their own land. Their opinions on land management are not strongly related to background factors or ideology (for example, gender, age, political party, wealth) but may be heavily influenced by personal experience with wildfire

A powerful visualization technique for electricity supply and demand at industrial sites with combined heat and power and wind generation

The combination of wind generation and combined heat and power (CHP) on an industrial site brings significant design and operational challenges. The stochastic nature of wind power affects the flows of electricity imported and exported to and from the site. Economies of scale favor larger wind turbines, but at the same time it is also desirable to minimize the amount of electricity exported from the site to avoid incurring increased network infrastructure usage charges. Therefore the optimum situation is to maximize the proportion of the site load served by on-site generation. This paper looks at a visualization technique for power flows on an industrial site, which can be used to size on-site generators. The technique is applied to a test case, demonstrating how a simple combined heat and power control scheme can support the integration of on-site wind power. The addition of such CHP control has a small impact on the CHP unit but can greatly increase the proportion of wind generation consumed on-site. This visualization technique allows the comparison of different generation mixes and control schemes in order to arrive at the optimal mix from a technical and economic viewpoint

Shwartzman reaction after human renal homotransplantation.

In three human recipients, five renal homografts were destroyed within a few minutes to hours after their revascularization in the new host. The kidneys, removed one to 54 days later, had cortical necrosis. The major vessels were patent, but the arterioles and glomeruli were the site of fibrin deposition. There was little or no fixation of host immunoglobulins in the homografts. The findings were characteristic of a generalized Shwartzman reaction. Although the cause (or causes) of the Shwartzman reaction in our patients is not known, they may have been conditioned by the bacterial contamination and hemolysis that often attend hemodialysis, by immunosuppression and by the transplantation itself. Some of the patients have preformed lymphocytotoxic antibodies. Thus, certain patients may be predisposed. High-risk patients should be recognized and treated prophylactically with anticoagulants