Evaluating connectivity risk of farm roadway runoff with waters - Development and sensitivity analysis of a semi quantitative risk model.

Farm roadways are an important sub-component of the nutrient transfer continuum (NTC) and roadway runoff (RR), leading to nutrient pressures in receiving waters at different times of the year at catchment scale. This study developed a semi-quantitative risk assessment model for dairy farms that once populated with data identifies roadway sections where RR enters waters. The model contains parameters that represent source, mobilisation and transport-connectivity stages of the NTC defined as continuous or categorical variables. Each parameter has a corresponding scoring system in terms of connectivity likelihood to waters (L) and the associated impact on water quality (I) from which field data can be converted to a risk score (RS). The connectivity or impact risk of any roadway section is a sum of all parameter scores, i.e. 'Total Risk Score' (TRS). The risk scores were classified into 5 categories (very low, low, moderate, high and very high). Field data from seven farms enabled five equal interval risk score classifications to be developed (very low (110-134), low (135-158), moderate (159-182), high (183-206), very high (207-230)). Fieldwork data showed differences between the number of mapped roadway sections ranging from 35 to 76, with the lowest and highest risk scores being 110 and 230, respectively. Out of all sections scored 25.9 %, 45.6 %, 20.4 %, 6.4 %, and 2 % were in very low, low, moderate, high and very high categories, respectively. In terms of management, only 8.4 % (i.e. high or very high scores) had all components of the NTC and required RR mitigation. An examination of the mobilisation parameter showed that the % of roadway sections needing mitigation is likely to increase if rainfall increases on these farms. An uncertainty assessment limiting the model to different levels of connectivity confirmed that all components of the NTC and those with greater than moderate risk should only be considered in future mitigation plans. Future work should concentrate on adapting this methodology to a wide range of farm enterprises.

Evaluation of allocation methods for calculation of carbon footprint of grass-based dairy production.

A major methodological issue for life cycle assessment, commonly used to quantify greenhouse gas emissions from livestock systems, is allocation from multifunctional processes. When a process produces more than one output, the environmental burden has to be assigned between the outputs, such as milk and meat from a dairy cow. In the absence of an objective function for choosing an allocation method, a decision must be made considering a range of factors, one of which is the availability and quality of necessary data. The objective of this study was to evaluate allocation methods to calculate the climate change impact of the economically average (€/ha) dairy farm in Ireland considering both milk and meat outputs, focusing specifically on the pedigree of the available data for each method. The methods were: economic, energy, protein, emergy, mass of liveweight, mass of carcass weight and physical causality. The data quality for each method was expressed using a pedigree score based on reliability of the source, completeness, temporal applicability, geographical alignment and technological appropriateness. Scenario analysis was used to compare the normalised impact per functional unit (FU) from the different allocation methods, between the best and worst third of farms (in economic terms, €/ha) in the national farm survey. For the average farm, the allocation factors for milk ranged from 75% (physical causality) to 89% (mass of carcass weight), which in turn resulted in an impact per FU, from 1.04 to 1.22 kg CO2-eq/kg (fat and protein corrected milk). Pedigree scores ranged from 6.0 to 17.1 with protein and economic allocation having the best pedigree. It was concluded that when making the choice of allocation method, the quality of the data available (pedigree) should be given greater emphasis during the decision making process because the effect of allocation on the results. A range of allocation methods could be deployed to understand the uncertainty associated with the decision.

A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables.

BACKGROUND: Early treatment for Crohn's disease (CD) with immunomodulators and/or anti-TNF agents improves outcomes in comparison to a slower 'step up' algorithm. However, there remains a limited ability to identify those who would benefit most from early intensive therapy. AIM: To develop a validated, individualised, web-based tool for patients and clinicians to visualise individualised risks for developing Crohn's disease complications. METHODS: A well-characterised cohort of adult patients with CD was analysed. Available data included: demographics; clinical characteristics; serologic immune responses; NOD2 status; time from diagnosis to complication; and medication exposure. Cox proportional analyses were performed to model the probability of developing a CD complication over time. The Cox model was validated externally in two independent CD cohorts. Using system dynamics analysis (SDA), these results were transformed into a simple graphical web-based display to show patients their individualised probability of developing a complication over a 3-year period. RESULTS: Two hundered and forty three CD patients were included in the final model of which 142 experienced a complication. Significant variables in the multivariate Cox model included small bowel disease (HR 2.12, CI 1.05-4.29), left colonic disease (HR 0.73, CI 0.49-1.09), perianal disease (HR 4.12, CI 1.01-16.88), ASCA (HR 1.35, CI 1.16-1.58), Cbir (HR 1.29, CI 1.07-1.55), ANCA (HR 0.77, CI 0.62-0.95), and the NOD2 frameshift mutation/SNP13 (HR 2.13, CI 1.33-3.40). The Harrell's C (concordance index for predictive accuracy of the model) = 0.73. When applied to the two external validation cohorts (adult n = 109, pediatric n = 392), the concordance index was 0.73 and 0.75, respectively, for adult and pediatric patients. CONCLUSIONS: A validated, web-based tool has been developed to display an individualised predicted outcome for adult patients with Crohn's disease based on clinical, serologic and genetic variables. This tool can be used to help providers and patients make personalised decisions about treatment options.

Field Effect and Strongly Localized Carriers in the Metal-Insulator Transition Material VO(2).

The intrinsic field effect, the change in surface conductance with an applied transverse electric field, of prototypal strongly correlated VO(2) has remained elusive. Here we report its measurement enabled by epitaxial VO(2) and atomic layer deposited high-κ dielectrics. Oxygen migration, joule heating, and the linked field-induced phase transition are precluded. The field effect can be understood in terms of field-induced carriers with densities up to ∼5×10(13) cm(-2) which are trongly localized, as shown by their low, thermally activated mobility (∼1×10(-3) cm(2)/V s at 300 K). These carriers show behavior consistent with that of Holstein polarons and strongly impact the (opto)electronics of VO(2).

Morning stiffness response with delayed-release prednisone after ineffective course of immediate-release prednisone.

OBJECTIVE: To assess morning stiffness in rheumatoid arthritis (RA) patients switched from immediate-release (IR) to delayed-release (DR) prednisone. METHOD: Circadian Administration of Prednisone in Rheumatoid Arthritis-1 (CAPRA-1) is a 12-week, randomized, multicentre, active-controlled study of morning stiffness that consisted of a double-blind phase and a 9-month open-label extension. Patients receiving IR prednisone with no significant improvement after the double-blind study were switched to DR prednisone. Morning stiffness duration and median absolute and relative changes in pain and global assessment were evaluated (3, 6, and 9 months). RESULTS: In patients switched from IR to DR prednisone (n=110), statistically significant reductions in morning stiffness occurred over 3 months and were sustained for 9 months. Absolute reduction of morning stiffness was ~50 min with >40% relative reduction at each visit. Interleukin (IL)-6 levels were reduced by the same amount. Statistically significant and clinically meaningful mean reductions in morning stiffness were maintained at >67 min at each visit along with significant improvements in pain and patient global assessment. There was no evidence of tachyphylaxis seen over the 9-month study. CONCLUSIONS: Patients receiving disease-modifying anti-rheumatic drugs (DMARDs) and IR prednisone who had not had significant reductions in morning stiffness demonstrated statistically significant and clinically meaningful improvements when switched to DR prednisone.

What Is the Relationship Between Morning Symptoms and Measures of Disease Activity in Patients With Rheumatoid Arthritis?

OBJECTIVE: Little is known about the relationship between morning symptoms of rheumatoid arthritis (RA) and measures of disease activity currently used to assess RA. Information available from the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-2) study was used to investigate these relationships. METHODS: CAPRA-2 included 350 patients with RA who were symptomatic despite treatment with disease-modifying antirheumatic drugs, randomized 2:1 to additional treatment with a 5-mg daily dose of delayed-release prednisone or placebo. Pearson's correlations were used to evaluate the relationships between change from baseline in symptoms (duration of morning stiffness, severity of morning stiffness, and intensity of pain on waking) and measures of disease activity (the American College of Rheumatology 20% improvement criteria [ACR20], the Disease Activity Score in 28 joints [DAS28], and the Health Assessment Questionnaire disability index). Correlations were defined as weak (<0.3), moderate (0.3-0.7), or strong (>0.7). RESULTS: There was a strong correlation between the severity of morning stiffness and the intensity of morning pain (Pearson's correlation 0.91, P < 0.001). There was a weak correlation between the duration of morning stiffness and measures of disease activity (0.24-0.28), with moderate correlations between the severity of morning stiffness or intensity of pain on waking and DAS28 or ACR20 scores (0.44-0.48). Severity of morning stiffness showed less variability and a greater effect size than did duration of morning stiffness. CONCLUSION: Morning symptoms and measures of disease activity show weak to moderate correlations. Severity of morning stiffness showed less variability and greater effect size than did duration of morning stiffness. These findings suggest that severity is the preferred construct to measure the impact of morning stiffness in patients with RA, information that is not fully captured in the RA core set.

Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations.

Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.

First record of dicephalia in a bull shark Carcharhinus leucas (Chondrichthyes: Carcharhinidae) foetus from the Gulf of Mexico, U.S.A.

The first recorded incidence of dicephalia in a bull shark Carcharhinus leucas is reported from a foetus collected by a fisherman in the Gulf of Mexico near Florida, U.S.A. External examination, Radiography and magnetic resonance imaging revealed a case of monosomic dicephalia where the axial skeleton and internal organs were found to divide into parallel systems anterior to the pectoral girdle resulting in two well-developed heads.

Immobilization mechanisms of deoxyribonucleic acid (DNA) to hafnium dioxide (HfO2) surfaces for biosensing applications.

Immobilization of biomolecular probes to the sensing substrate is a critical step for biosensor fabrication. In this work we investigated the phosphate-dependent, oriented immobilization of DNA to hafnium dioxide surfaces for biosensing applications. Phosphate-dependent immobilization was confirmed on a wide range of hafnium oxide surfaces; however, a second interaction mode was observed on monoclinic hafnium dioxide. On the basis of previous materials studies on these films, DNA immobilization studies, and density functional theory (DFT) modeling, we propose that this secondary interaction is between the exposed nucleobases of single stranded DNA and the surface. The lattice spacing of monoclinic hafnium dioxide matches the base-to-base pitch of DNA. Monoclinic hafnium dioxide is advantageous for nanoelectronic applications, yet because of this secondary DNA immobilization mechanism, it could impede DNA hybridization or cause nonspecific surface intereactions. Nonetheless, DNA immobilization on polycrystalline and amorphous hafnium dioxide is predominately mediated by the terminal phosphate in an oriented manner which is desirable for biosensing applications.

Thyroid dysfunction and fibrin network structure: a mechanism for increased thrombotic risk in hyperthyroid individuals.

CONTEXT: Hyperthyroidism is associated with increased thrombosis risk, and fibrin clot structure determines susceptibility to vascular thrombotic events. OBJECTIVE: Our objective was to investigate clot formation and lysis in hyperthyroidism using observational and interventional studies. DESIGN: Ex vivo fibrin clot structure/fibrinolysis and plasma levels of thrombotic/inflammatory markers were investigated in hyperthyroid individuals (n = 24) and matched controls (n = 19), using turbidimetric assays, ELISA, and confocal and electron microscopy. The effects of normalizing thyroid function were analyzed (n = 19) and the role of short-term exogenous hyperthyroidism in healthy volunteers studied (n = 16). RESULTS: Hyperthyroid subjects displayed higher clot maximum absorbance compared with controls (0.41 ± 0.03 and 0.27 ± 0.01 arbitrary units, respectively; P < 0.01), and longer clot lysis time (518 ± 23 and 461 ± 18 sec, respectively; P < 0.05), which correlated with free T(4) levels. Plasma levels of fibrinogen and plasminogen activator inhibitor-1 were significantly higher in patients compared with controls. Normalizing thyroid function in 19 subjects was associated with lower maximum absorbance and shorter lysis time, accompanied by reduction in fibrinogen, plasminogen activator inhibitor-1, and D-dimer levels. Complement C3, but not C-reactive protein, levels were higher in hyperthyroid subjects compared with controls (0.92 ± 0.05 and 0.64 ± 0.03 g/liter, respectively; P < 0.01), correlated with clot structure parameters, and decreased after intervention. Confocal and electron microscopy confirmed more compact clots and impaired fibrinolysis during hyperthyroidism. Exogenous hyperthyroidism in healthy volunteers had no effect on any of the clot structure parameters. CONCLUSIONS: Endogenous hyperthyroidism is associated with more compact clots and resistance to fibrinolysis ex vivo, related to the degree of hyperthyroidism and C3 plasma levels, and these changes are modulated by achieving euthyroidism. Altered clot structure/lysis may be one mechanism for increased thrombotic risk in hyperthyroidism.

LIAD-fs scheme for studies of ultrafast laser interactions with gas phase biomolecules.

Laser induced acoustic desorption (LIAD) has been used for the first time to study the parent ion production and fragmentation mechanisms of a biological molecule in an intense femtosecond (fs) laser field. The photoacoustic shock wave generated in the analyte substrate (thin Ta foil) has been simulated using the hydrodynamic HYADES code, and the full LIAD process has been experimentally characterised as a function of the desorption UV-laser pulse parameters. Observed neutral plumes of densities >10(9) cm(-3) which are free from solvent or matrix contamination demonstrate the suitability and potential of the source for studying ultrafast dynamics in the gas phase using fs laser pulses. Results obtained with phenylalanine show that through manipulation of fundamental femtosecond laser parameters (such as pulse length, intensity and wavelength), energy deposition within the molecule can be controlled to allow enhancement of parent ion production or generation of characteristic fragmentation patterns. In particular by reducing the pulse length to a timescale equivalent to the fastest vibrational periods in the molecule, we demonstrate how fragmentation of the molecule can be minimised whilst maintaining a high ionisation efficiency.

A brief report on perceptions of alcohol and society among Scottish medical students.

AIMS: To assess perceptions on alcohol misuse and addiction among medical students prior to in-depth training in order to determine areas of the curriculum that need to be reshaped or focused on. METHODS: A questionnaire assessment of first- and second-year medical students' perceptions of alcohol misuse. RESULTS: Students had some misconceptions about current alcohol misuse rates, including a perception that addiction is common among health professionals, that the under-25s had the fastest increasing rate of alcohol addiction and that British women had a more rapidly increasing rate of alcohol addiction than British men. CONCLUSION: Encouragingly, students overwhelmingly felt that alcohol addiction was something to which they could make a difference. It highlights that early education about alcohol misuse is important in terms of teaching students how to recognize hazardous and harmful drinkers and how to manage them.

Human uric acid transporter 1 (hURAT1): an inhibitor structure-activity relationship (SAR) study.

The current study describes the chemical synthesis of a series of (2-ethylbenzofuran-3-yl)(substituted-phenyl)methanone compounds and their subsequent in vitro testing via oocytes expressing hURAT1. The experimental data support the notion that a potent hURAT1 inhibitor requires an anion (i.e., a formal negative charge) to interact with the positively charged hURAT1 binding pocket. An anion appears to be a primary requirement in order to be a hURAT1 substrate (i.e., urate) or inhibitor. We discuss the inhibitor structure-activity relationship and how electronically donating or withdrawing groups attached to the B-ring can decrease or increase inhibitory potency, respectively.

HIV point-of-care testing pitfalls.

When counselling patients for postexposure prophylaxis after sexual exposure, we may need to inform them that the efficacy may be low, especially if the patient also had risks prior to the 72 hours between exposure and treatment. The use of a point-of-care test, as well as fourth generation HIV tests and HIV RNA in combination, can still miss seroconversion in the 'eclipse' phase of the infection as these tests are not designed to detect the earliest phase of infection.

The injured lung: clinical issues and experimental models.

Exposure of military and civilian populations to inhaled toxic chemicals can take place as a result of deliberate release (warfare, terrorism) or following accidental releases from industrial concerns or transported chemicals. Exposure to inhaled toxic chemicals can result in an acute lung injury, and in severe cases acute respiratory distress syndrome, for which there is currently no specific medical therapy, treatment remaining largely supportive. This treatment often requires intensive care facilities that may become overwhelmed in mass casualty events and may be of limited benefit in severe cases. There remains, therefore, a need for evidence-based treatment to inform both military and civilian medical response teams on the most appropriate treatment for chemically induced lung injury. This article reviews data used to derive potential clinical management strategies for chemically induced lung injury.

Evaluation of a new core curriculum on alcohol use disorders for undergraduate medical students.

AIMS: This study was aimed to review and rewrite the undergraduate curriculum on alcohol use disorders, implement the changes and assess for any early evidence of an improvement in knowledge. METHODS: A three-stage process was used to review the old curriculum and a new one was designed around the five undergraduate years. Students' opinions were sought about the acceptability of the new curriculum using a questionnaire, to which 93 responded and 70 volunteers were objectively assessed using an examination based on questions from the text of the Medical Students' Handbook on Alcohol and Health. RESULTS: There was no evidence of any improvement in the students' knowledge using the old curriculum. After teaching with the new curriculum, examination scores significantly increased (P < 0.0001). There was no difference between the sexes. The new curriculum was assessed as acceptable to the students. CONCLUSION: This new curriculum reflects the need for a new teaching method and not only offers improved teaching, but also produces a generation of doctors equipped to identify alcohol-related problems and to deliver brief interventions, helping to reduce the projected consequences of alcohol abuse and the associated burden on the health service.

Delayed low-dose supplemental oxygen improves survival following phosgene-induced acute lung injury.

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces life-threatening pulmonary edema within hours of exposure; no antidote exists. This study examines pathophysiological changes seen following treatment with elevated inspired oxygen concentrations (Fi(O2)), in a model of phosgene-induced acute lung injury. Anesthetized pigs were exposed to phosgene (Ct 2500 mg min m(-3)) and ventilated (intermittent positive pressure ventilation, tidal volume 10 ml kg(-1), positive end-expiratory pressure 3 cm H(2)O, frequency 20 breaths min(-1)). The Fi(O2) was varied: group 1, Fi(O2) 0.30 (228 mm Hg) throughout; group 2, Fi(O2) 0.80 (608 mm Hg) immediately post exposure, to end; group 3, Fi(O2) 0.30 from 30 min post exposure, increased to 0.80 at 6 h post exposure; group 4, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 (304 mm Hg) at 6 h post exposure. Group 5, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 at 12 h post exposure. The current results demonstrate that oxygen is beneficial, with improved survival, arterial oxygen saturation, shunt fraction, and reduced lung wet weight to body weight ratio in all treatment groups, and improved arterial oxygen partial pressure in groups 2 and 3, compared to phosgene controls (group 1) animals. The authors recommend that treatment of phosgene-induced acute lung injury with inspired oxygen is delayed until signs or symptoms of hypoxia are present or arterial blood oxygenation falls. The lowest concentration of oxygen that maintains normal arterial oxygen saturation and absence of clinical signs of hypoxia is recommended.

Furosemide in the treatment of phosgene induced acute lung injury.

METHOD: Using previously validated methods, 16 anaesthetised large white pigs were exposed to phosgene (target inhaled dose 0.3 mg kg(-1)), established on mechanical ventilation and randomised to treatment with either nebulised furosemide (4 ml of 10 mg x ml(-1) solution) or saline control. Treatments were given at 1, 3, 5, 7, 9, 12, 16 and 20 hours post phosgene exposure; the animals were monitored to 24 hours following phosgene exposure. RESULTS: Furosemide treatment had no effect on survival, and had a deleterious effect on PaO2: FiO2 ratio between 19 and 24 hours. All other measures investigated were unaffected by treatment. CONCLUSION: Nebulised furosemide treatment following phosgene induced acute lung injury does not improve survival and worsens PaO2: FiO2 ratio. Nebulised furosemide should be avoided following phosgene exposure.

Supercritical biodiesel production and power cogeneration: technical and economic feasibilities.

An integrated supercritical fluid technology with power cogeneration to produce biodiesel fuels, with no need for the costly separations involved with the conventional technology, is proposed, documented for technical and economic feasibility, and preliminarily designed. The core of the integrated system consists of the transesterification of various triglyceride sources (e.g., vegetable oils and animal fats) with supercritical methanol/ethanol. Part of the reaction products can be combusted by a diesel power generator integrated in the system which, in turn, provides the power needed to pressurize the system and the heat of the exhaust gases necessary in the transesterification step. The latter energy demand can also be satisfied by a fired heater, especially for higher plant capacities. Different versions of this system can be implemented based on the main target of the technology: biodiesel production or diesel engine applications, including power generation. The process options considered for biodiesel fuel production estimate break-even processing costs of biodiesel as low as $0.26/gal ($0.07/L) with a diesel power generator and $0.35/gal ($0.09/L) with a fired heater for a plant capacity of 15,000 gal/day (56,775 L/day). Both are significantly lower than the current processing costs of approximately $0.51/gal ($0.13/L) of biodiesel produced by conventional catalytic methods. A retail cost of biodiesel produced by the proposed method is likely to be competitive with the prices of diesel fuels.