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.

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.

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.

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.

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.

Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune serum.

Neisseria gonorrhoeae that resist complement-dependent killing by normal human serum (NHS) are sometimes killed by immune convalescent serum from patients recovering from disseminated gonococcal infection (DGI). In these studies, killing by immune serum was prevented or blocked by IgG isolated from NHS. Purified human IgG antibodies directed against gonococcal protein III, an antigenically conserved outer membrane protein, contained most of the blocking activity in IgG. Antibodies specific for gonococcal porin (protein I), the major outer membrane protein, displayed no blocking function. In separate experiments, immune convalescent DGI serum which did not exhibit bactericidal activity was restored to killing by selective depletion of protein III antibodies by immunoabsorption. These studies indicate that protein III antibodies in normal and immune human serum play a role in serum resistance of N. gonorrhoeae.

Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae.

Neisseria gonorrhoeae isolated from patients with disseminated infection are often of the porin (Por1A) serotype and resist killing by nonimmune normal human serum. The molecular basis of this resistance (termed stable serum resistance) in these strains has not been fully defined but is not related to sialylation of lipooligosaccharide. Here we demonstrate that Por1A bearing gonococcal strains bind more factor H, a critical downregulator of the alternative complement pathway, than their Por1B counterparts. This results in a sevenfold reduction in C3b, which is >75% converted to iC3b. Factor H binding to isogenic gonococcal strains that differed only in their porin serotype, confirmed that Por1A was the acceptor molecule for factor H. We identified a surface exposed region on the Por1A molecule that served as the binding site for factor H. We used gonococcal strains with hybrid Por1A/B molecules that differed in their surface exposed domains to localize the factor H binding site to loop 5 of Por1A. This was confirmed by inhibition of factor H binding using synthetic peptides corresponding to the putative exposed regions of the porin loops. The addition of Por1A loop 5 peptide in a serum bactericidal assay, which inhibited binding of factor H to the bacterial surface, permitted 50% killing of an otherwise completely serum resistant gonococcal strain. Collectively, these data provide a molecular basis to explain serum resistance of Por1A strains of N. gonorrhoeae.

Conservation of the lipooligosaccharide synthesis locus lgt among strains of Neisseria gonorrhoeae: requirement for lgtE in synthesis of the 2C7 epitope and of the beta chain of strain 15253.

The present study was undertaken to examine the extent to which the lgt locus varies among strains of gonococci. This locus encodes five glycosyl transferases involved in the synthesis of the lipooligosaccharide (LOS) of Neisseria gonorrhoeae. We examined seven gonococcal strains and found that the structure of the lgt locus is conserved among six of these strains. The locus is strikingly altered in strain 15253. This is one of the few strains where extensive structural analysis of its LOS is available, and therefore, we defined the altered lgt locus and focused on the reactivity of mAB 2C7. We found that strain 15253 contains only two lgt genes, lgtA and lgtE. As in F62, lgtA encodes a GlcNAc transferase and is subject to phase variation. In addition, by analysis of deletion mutants, we found that lgtE, which encodes a galactosyl transferase that is required for elongating the alpha-chain, is also necessary for completing the beta chain.

A novel sialic acid binding site on factor H mediates serum resistance of sialylated Neisseria gonorrhoeae.

Factor H (fH), a key alternative complement pathway regulator, is a cofactor for factor I-mediated cleavage of C3b. fH consists of 20 short consensus repeat (SCR) domains. Sialic acid binding domains have previously been localized to fH SCRs 6-10 and 13. To examine fH binding on a sialylated microbial surface, we grew Neisseria gonorrhoeae in the presence of 5'-cytidinemonophospho-N-acetylneuraminic acid, which sialylates lipooligosaccharide and converts to serum resistance gonococci previously sensitive to nonimmune serum killing. fH domains necessary for binding sialylated gonococci were determined by incubating organisms with recombinant human fH (rH) and nine mutant rH molecules (deletions spanning the entire fH molecule). rH and all mutant rH molecules that contained SCRs 16-20 bound to the sialylated strain; no mutant molecule bound to serum-sensitive nonsialylated organisms. Sialic acid was demonstrated to be the fH target by flow cytometry that showed a fourfold increase in fH binding that was reversed by neuraminidase-mediated cleavage of sialic acid off gonococci. Functional specificity of fH was confirmed by decreased total C3 binding and almost complete conversion to iC3b on sialylated gonococci. Sialic acid can therefore bind fH uniquely through SCRs 16-20. This blocks complement pathway activation for N. gonorrhoeae at the level of C3.

Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae.

We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-binding protein (C4bp). Microbial surface-bound C4bp demonstrated cofactor activity. We constructed gonococcal strains with hybrid porin (Por) molecules derived from each of the major serogroups (Por1A and Por1B) of N. gonorrhoeae, and showed that the loop 1 of Por1A is required for C4bp binding. Por1B loops 5 and 7 of serum-resistant gonococci together formed a negatively charged C4bp-binding domain. C4bp-Por1B interactions were ionic in nature (inhibited by high salt or by heparin), whereas the C4bp-Por1A bond was hydrophobic. Only recombinant C4bp mutant molecules containing the NH2-terminal alpha-chain short consensus repeat (SCR1) bound to both Por1A and Por1B gonococci, suggesting that SCR1 contained Por binding sites. C4bp alpha-chain monomers did not bind gonococci, indicating that the polymeric form of C4bp was required for binding. Using fAb fragments against C4bp SCR1, C4bp binding to Por1A and Por1B strains was inhibited in a complement-dependent serum bactericidal assay. This resulted in complete killing of these otherwise fully serum resistant strains in only 10% normal serum, underscoring the importance of C4bp in mediating gonococcal serum resistance.

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.

Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor.

A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66-kilodalton subunit has a large cleft analogous to that of the Klenow fragment of Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of identical sequence has no such cleft because the four subdomains of the pol domain occupy completely different relative positions. Two of the four pol subdomains appear to be structurally related to subdomains of the Klenow fragment, including one containing the catalytic site. The subdomain that appears likely to bind the template strand at the pol active site has a different structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built into the cleft that runs between the ribonuclease H and pol active sites. Nevirapine is almost completely buried in a pocket near but not overlapping with the pol active site. Residues whose mutation results in drug resistance have been approximately located.

Mayan urbanism: impact on a tropical karst environment.

From the first millennium B.C. through the 9th-century A.D. Classic Maya collapse, nonurban populations grew exponentially, doubling every 408 years, in the twin-lake (Yaxha-Sacnab) basin that contained the Classic urban center of Yaxha. Pollen data show that forests were essentially cleared by Early Classic time. Sharply accelerated slopewash and colluviation, amplified in the Yaxha subbasin by urban construction, transferred nutrients plus calcareous, silty clay to both lakes. Except for the urban silt, colluvium appearing as lake sediments has a mean total phosphorus concentration close to that of basin soils. From this fact, from abundance and distribution of soil phosphorus, and from continuing post-Maya influxes (80 to 86 milligrams of phosphorus per square meter each year), which have no other apparent source, we conclude that riparian soils are anthrosols and that the mechanism of long-term phosphorus loading in lakes is mass transport of soil. Per capita deliveries of phosphorus match physiological outputs, approximately 0.5 kilogram of phosphorus per capita per year. Smaller apparent deliveries reflect the nonphosphatic composition of urban silt; larger societal outputs, expressing excess phosphorus from deforestation and from food waste and mortuary disposal, are probable but cannot be evaluated from our data. Eutrophication is not demonstrable and was probably impeded, even in less-impacted lakes, by suspended Maya silt. Environmental strain, the product of accelerating agroengineering demand and sequestering of nutrients in colluvium, developed too slowly to act as a servomechanism, damping population growth, at least until Late Classic time.

Fabrication and characterization of a carbon nanotube-based nanoknife.

We demonstrate the fabrication and testing of a prototype microtome knife based on a multiwalled carbon nanotube (MWCNT) for cutting approximately 100 nm thick slices of frozen-hydrated biological samples. A piezoelectric-based 3D manipulator was used inside a scanning electron microscope (SEM) to select and position individual MWCNTs, which were subsequently welded in place using electron beam-induced deposition. The knife is built on a pair of tungsten needles with provision to adjust the distance between the needle tips, accommodating various lengths of MWCNTs. We performed experiments to test the mechanical strength of a MWCNT in the completed device using an atomic force microscope tip. An increasing force was applied at the mid-point of the nanotube until failure occurred, which was observed in situ in the SEM. The maximum breaking force was approximately (8 x 10(-7)) N which corresponds well with the typical microtome cutting forces reported in the literature. In situ cutting experiments were performed on a cell biological embedding plastic (epoxy) by pushing it against the nanotube. Initial experiments show indentation marks on the epoxy surface. Quantitative analysis is currently limited by the surface asperities, which have the same dimensions as the nanotube.

Excessive use of force by police: a survey of academic emergency physicians.

OBJECTIVE: To determine the clinical experience, management and training of emergency physicians in the suspected use of excessive force by law enforcement officers. METHODS: Surveys were mailed to a random sample of academic emergency physicians in the USA. RESULTS: Of 393 emergency physicians surveyed, 315 (80.2%) responded. Of the respondents, 99.8% (95% CI 98.2% to 100.0%) believed excessive use of force actually occurs and 97.8% (95% CI 95.5% to 99.1%) replied that they had managed patients with suspected excessive use of force. These incidents were not reported by 71.2% (95% CI 65.6% to 76.4%) of respondents, 96.5% (95% CI 93.8% to 98.2%) had no departmental policies and 93.7% (95% CI 90.4% to 96.1%) had not received training in the management of these cases. CONCLUSIONS: Suspected excessive use of force is encountered by academic emergency physicians in the USA. There is only limited training or policies for the management of these cases.