Low risk management intervention: Limited impact of remedial tillage on net ecosystem carbon balance at a commercial Miscanthus plantation.

Perennial bioenergy crops are a key tool in decarbonizing global energy systems, but to ensure the efficient use of land resources, it is essential that yields and crop longevity are maximized. Remedial shallow surface tillage is being explored in commercial Miscanthus plantations as an approach to reinvigorate older crops and to rectify poor establishment, improving yields. There are posited links, however, between tillage and losses in soil carbon (C) via increased ecosystem C fluxes to the atmosphere. As Miscanthus is utilized as an energy crop, changes in field C fluxes need to be assessed as part of the C balance of the crop. Here, for the first time, we quantify the C impacts of remedial tillage at a mature commercial Miscanthus plantation in Lincolnshire, United Kingdom. Net ecosystem C production based on eddy covariance flux observations and exported yield totalled 12.16 Mg C ha-1 over the 4.6 year period after tillage, showing the site functioned as a net sink for atmospheric carbon dioxide (CO2). There was no indication of negative tillage induced impacts on soil C stocks, with no difference 3 years post tillage in the surface (0-30 cm) or deep (0-70 cm) soil C stocks between the tilled Miscanthus field and an adjacent paired untilled Miscanthus field. Comparison to historic samples showed surface soil C stocks increased by 11.16 ± 3.91 Mg C ha-1 between pre (October 2011) and post tillage sampling (November 2016). Within the period of the study, however, the tillage did not result in the increased yields necessary to "pay back" the tillage induced yield loss. Rather the crop was effectively re-established, with progressive yield increases over the study period, mirroring expectations of newly planted sites. The overall impacts of remedial tillage will depend therefore, on the longer-term impacts on crop longevity and yields.

Critical review of the impacts of grazing intensity on soil organic carbon storage and other soil quality indicators in extensively managed grasslands.

Livestock grazing intensity (GI) is thought to have a major impact on soil organic carbon (SOC) storage and soil quality indicators in grassland agroecosystems. To critically investigate this, we conducted a global review and meta-analysis of 83 studies of extensive grazing, covering 164 sites across different countries and climatic zones. Unlike previous published reviews we normalized the SOC and total nitrogen (TN) data to a 30 cm depth to be compatible with IPCC guidelines. We also calculated a normalized GI and divided the data into four main groups depending on the regional climate (dry warm, DW; dry cool, DC; moist warm, MW; moist cool, MC). Our results show that taken across all climatic zones and GIs, grazing (below the carrying capacity of the systems) results in a decrease in SOC storage, although its impact on SOC is climate-dependent. When assessed for different regional climates, all GI levels increased SOC stocks under the MW climate (+7.6%) whilst there were reductions under the MC climate (-19%). Under the DW and DC climates, only the low (+5.8%) and low to medium (+16.1%) grazing intensities, respectively, were associated with increased SOC stocks. High GI significantly increased SOC for C4-dominated grassland compared to C3-dominated grassland and C3-C4 mixed grasslands. It was also associated with significant increases in TN and bulk density but had no effect on soil pH. To protect grassland soils from degradation, we recommend that GI and management practices should be optimized according to climate region and grassland type (C3, C4 or C3-C4 mixed).

Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study.

OBJECTIVES: Osteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin. METHODS: In this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B). RESULTS: ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. CONCLUSIONS: Osteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.

Near-patient platelet function testing in patients undergoing coronary artery surgery: a pilot study.

Platelet dysfunction after cardiopulmonary bypass contributes to microvascular bleeding and is associated with blood transfusion and resternotomy. Platelet count can be readily performed, but currently there are no standardised, reproducible, rapidly available platelet function tests. We studied platelet function as measured by multiple electrode platelet aggregometery (multiplate) and light transmission aggregometry in 44 patients undergoing routine coronary artery surgery. Platelet aggregation as measured by multiplate was reduced during and after cardiopulmonary bypass compared with baseline with evidence of partial recovery by the time of transfer to ITU. In patients transfused blood, platelet aggregation measured by multiplate was reduced during chest closure with adenosine diphosphate (18 U vs 29 U, p = 0.01) and thrombin receptor agonist peptide-6 agonist (65 U vs 88 U, p = 0.01) compared with patients not transfused. This suggests that multiplate, a new point of care analyser, can detect platelet dysfunction in this setting.

Measurement of intermodulation distortion in high-linearity photodiodes.

Accurately characterizing third order intermodulation distortion (IMD3) in high-linearity photodiodes is challenging. Two measurement techniques are evaluated-a standard two-tone measurement and a more complicated three-tone measurement technique to measure IMD3. A model of the measurement system is developed and used to analyze the limitations of the two techniques in determining the distortion of highly linear photodiodes. Experimental validation is provided by comparing the simulation trends with IMD3 results measured on two types of waveguide photodiodes: 1) an InP based uni-traveling-carrier (UTC) photodiode and 2) a Ge n-i-p waveguide photodetector on Silicon-on-Insulator (SOI) substrate.

Ecosystem engineers: feedback and population dynamics.

All organisms alter their abiotic environment, but ecosystem engineers are species with abiotic effects that may have to be explicitly accounted for when making predictions about population and community dynamics. The goal of this analysis is to identify those conditions in which engineering leads to population dynamics that are qualitatively different than one would predict using models that incorporate only biotic interactions. We present a simple model coupling an ecosystem engineer and the abiotic environment. We assume that the engineer alters environmental conditions at a rate dependent on engineer density and that the environment decays back to original conditions at an exponential rate. We determine when the feedback to population dynamics through environmental state can lead to altered equilibrium densities, bistability, or runaway growth of the engineer population. The conditions leading to changes in dynamics, such as susceptibility of a system to engineering or alteration of density-dependent and density-independent controls, define cases in which the engineering concept is essential for ecological understanding.

Teaching and Assessing Consultation Skills : an Evaluation of a South African workshop on using the Leicester Assessment Package

Background: Alcohol is the most important substance of abuse in South Africa. There are; however; reports of an increase in the use of other drugs among adolescents. The aim of this study was to assess the use of alcohol and other drugs of abuse and their association with physical or sexual abuse in three urban high schools in Mthatha. MethodThe Alcohol Use Disorders Identification Test (AUDIT); embedded in a broader questionnaire; was used as a screening tool to assess primary and secondary objectives among the student population (N = 1 424) attending school on a given day at three urban high schools in Mthatha (a cut-off point of 8 was selected).Results: Of the 266 (18.6) students who tested AUDIT positive; 63 (4.42) were female and 203 (14.26) were male (P less than 0.01). AUDIT-positive students between the ages of 15 and 17 years represent 10.18 of the total number of students tested. A total of 169 (11.87) students showed symptoms of dependence; while 355 students (24.93) reported drug-related problems in their families. Two hundred and twenty-five (15.8) of the students admitted using dagga (cannabis) at some point; while 69 (4.85) had used mandrax and 64 (4.49) had used cocaine. A total of 149 (10.46) students had been victims of physical abuse and 91 (6.39) of sexual abuse. Sexual and physical abuses were statistically significantly correlated with alcohol-related problems.Conclusions: Alcohol was the most commonly abused drug in the screened group; followed by cannabis; mandrax and cocaine. Sexually or physically abused students were at a higher risk of developing a substance-related problem

The impact of single cysteine residue mutations on the replication terminator protein.

We report the structural and biophysical consequences of cysteine substitutions in the DNA-binding replication terminator protein (RTP) of Bacillus subtilis, that resulted in an optimised RTP mutant suitable for structural studies. The cysteine residue 110 was replaced with alanine, valine or serine. Protein secondary structure and stability (using circular dichroism spectropolarimetry), self-association (using analytical ultracentrifugation), and DNA-binding measurements revealed RTP.C110S to be the most similar mutant to wild-type RTP. The C110A and C110V.RTP mutants were less soluble, less stable and showed lower DNA-binding affinity. The structure of RTP.C110S, solved to 2.5A resolution using crystallographic methods, showed no major structural perturbation due to the mutation. Heteronuclear NMR spectroscopic studies revealed subtle differences in the electronic environment about the site of mutation. The study demonstrates the suitability of serine as a substitute for cysteine in RTP and the high sensitivity of protein behaviour to single amino acid substitutions.

GP stress and patient dissatisfaction with nights on call: an exploratory study. GP stress and patient satisfaction.

OBJECTIVES: To compare the relative effects of being on or off duty at night on general practitioners' (GPs') levels of stress, and the satisfaction of their patients with daytime consultations surrounding these nights. DESIGN: A within-subjects, counterbalanced design was used. Two "on-call" and two "off-duty" nights were studied per GP over 4 weeks. SETTING: Primary health care in the UK. PARTICIPANTS: 26 GPs and their patients seen in consultations either side of nights studied. MAIN OUTCOME MEASURES: GPs completed validated stress questionnaires at the beginning and end of the consultation sessions immediately before and after nights on call and off duty. RESULTS: GPs experienced elevated levels of stress when on call, compared to when they were off duty. Patients seen in the consultation sessions before and after a night on call were less satisfied than patients seen before and after a night off duty. CONCLUSION: Being on call at night raised GP stress levels from at least the start of the afternoon consultation session before until the end of the morning consultation after the night on call. Daytime patient satisfaction is also reduced in periods surrounding nights on call.

Structure of the RTP-DNA complex and the mechanism of polar replication fork arrest.

The coordinated termination of DNA replication is an important step in the life cycle of bacteria with circular chromosomes, but has only been defined at a molecular level in two systems to date. Here we report the structure of an engineered replication terminator protein (RTP) of Bacillus subtilis in complex with a 21 base pair DNA by X-ray crystallography at 2.5 A resolution. We also use NMR spectroscopic titration techniques. This work reveals a novel DNA interaction involving a dimeric 'winged helix' domain protein that differs from predictions. While the two recognition helices of RTP are in close contact with the B-form DNA major grooves, the 'wings' and N-termini of RTP do not form intimate contacts with the DNA. This structure provides insight into the molecular basis of polar replication fork arrest based on a model of cooperative binding and differential binding affinities of RTP to the two adjacent binding sites in the complete terminator.

Dimensional approaches to scaling experimental ecosystems: designing mousetraps to catch elephants.

Enclosed experimental ecosystems (mesocosms) are small relative to their natural counterparts, are typically operated for short durations relative to the timescales of a number of important ecological processes, and also often have reduced biological and physical complexity relative to nature. These reductions in time, space, and complexity scales have been cited as sources of unrealistic ecological behavior within mesocosms and raise questions about extrapolating results from mesocosms to nature. Dimensional analysis, a technique widely used by engineers to create scale models, uses compensatory distortion as a means of maintaining dynamic similarity in properties and relationships of interest. Although biological parameters are generally less controllable than physical ones, a variety of dimensional approaches can be taken to maintain such key ecological properties as effective habitat size, environmental variability, vertical and horizontal gradients, interactions among habitats, and control of experimental artifacts. To date, application of dimensional approaches to mesocosm design has been largely intuitive and idiosyncratic. We argue that a more explicit, systematic, and quantitative approach will increase realism and may also provide a critical means of developing, testing, and advancing our understanding of scaling relationships in nature.

Formative assessment of the consultation performance of medical students in the setting of general practice using a modified version of the leicester assessment package.

OBJECTIVE: To evaluate the use of a modified version of the Leicester Assessment Package (LAP) in the formative assessment of the consultation performance of medical students with particular reference to validity, inter-assessor reliability, acceptability, feasibility and educational impact. DESIGN: 180 third and fourth year Leicester medical students were directly observed consulting with six general practice patients and independently assessed by a pair of assessors. A total of 70 practice and 16 departmental assessors took part. Performance scores were subjected to generalizability analysis and students' views of the assessment were gathered by questionnaire. RESULTS: Four of the five categories of consultation performance (Interviewing and history taking, Patient management, Problem solving and Behaviour and relationship with patients) were assessed in over 99% of consultations and Physical examination was assessed in 94%. Seventy-six percent of assessors reported that the case mix was 'satisfactory' and 20% that it was 'borderline'; 85% of students believed it to have been satisfactory. Generalizability analysis indicates that two independent assessors assessing the performance of students across six consultations would achieve a reliability of 0.94 in making pass or fail decisions. Ninety-eight percent of students perceived that their particular strengths and weaknesses were correctly identified, 99% that they were given specific advice on how to improve their performance and 98% believed that the feedback they had received would have long-term benefit. CONCLUSIONS: The modified version of the LAP is valid, reliable and feasible in formative assessment of the consultation performance of medical students. Furthermore, almost all students found the process fair and believed it was likely to lead to improvements in their consultation performance. This approach may also be applicable to regulatory assessment as it accurately identifies students at the pass/fail margin.

Population outbreaks in a discrete world.

We present and analyze a simple three-patch host-parasitoid model where population growth is discrete. The model gives solutions that are qualitatively similar to the stable large-amplitude patterns in space found in reaction-diffusion theory. In the context of host-parasitoid interactions, the large-amplitude portions of the solution can be thought of as spatially localized host population outbreaks. Here, we show that the biological requirements for localized population outbreaks in a discrete world are identical to those found in reaction- diffusion theory. Furthermore, the model conveniently allows investigation into the robustness of these population outbreaks under the influence of density-dependent dispersal behavior. We find that localized population outbreaks in space can still occur with modest amounts of pursuit and aggregative behavior by parasitoids. We end by showing that evidence from a real host-parasitoid system is consistent with the predictions of the model.

Investigation of the relocation of cytosolic phospholipase A2 and annexin V in activated platelets.

Cytosolic phospholipase A(2) is a Ca(2+)-dependent enzyme that acts on membrane phospholipids to release arachidonic acid, which in platelets is converted to thromboxane A(2). Annexin V is a Ca(2+)-dependent, phospholipid-binding protein, which is proposed to regulate inflammation by inhibiting cytosolic phospholipase A(2). Here, we have studied the association of cytosolic phospholipase A(2) and annexin V with platelet membranes after thrombin stimulation. In a time-dependent manner, an exact correlation was found between the membrane association of cytosolic phospholipase A(2) and annexin V. Calcium from the intracellular stores was sufficient for the relocation of intracellular annexin V and cytosolic phospholipase A(2) to platelet membranes. Activation in the presence of arginyl-glycyl-aspartyl-serine (RGDS), which inhibits binding of fibrinogen to its adhesive ligand, does not alter the amount of cytosolic phospholipase A(2) or annexin V that binds to membranes. When activation-induced actin polymerisation was prevented by cytochalasin E, the recovery of both annexin V and cytosolic phospholipase A(2) remained unchanged. However, complete depolymerisation of the cytoskeleton with DNase I almost abolished the association of cytosolic phospholipase A(2) with the membranes, and it completely abolished the relocation of annexin V to platelet membranes. Finally, we show that cytosolic phospholipase A(2) can be specifically purified from platelet membranes by affinity chromatography on GST-annexin V and that immunoprecipitation using antibodies against cytosolic phospholipase A(2) copurify annexin V and cytosolic phospholipase A(2) from activated platelets. These findings suggest that following platelet activation with thrombin, both cytosolic phospholipase A(2) and annexin V, relocate to platelet membranes where they interact. An intact cytoskeleton seems to be a prerequisite for the interaction of cytosolic phospholipase A(2) and annexin V with platelet membranes. The incorporation of cytosolic phospholipase A(2) into the membrane fraction of thrombin-activated platelets parallels that of annexin V, which suggests an interaction between the two proteins.