Effects of acute alkalosis and acidosis on performance

Ingestion of agents that modify blood buffering action may affect high-intensity performance. Here we present a meta-analysis of the effects of acute ingestion of three such agents - sodium bicarbonate, sodium citrate and ammonium chloride - on performance and related physiological variables (blood bicarbonate, pH and lactate). A literature search yielded 59 useable studies with 188 observations of performance effects. To perform the mixed- model meta-analysis, all performance effects were converted into a percentage change in mean power and were weighted using standard errors derived from exact p-values, confidence limits (CLs) or estimated errors of measurement. The fixed effects in the meta-analytic model included the number of performance-test bouts (linear), test duration (log linear), blinding (yes/no), competitive status (athiete/nonathlete) and sex (male/female). Dose expressed as buffering mmoL/kg/body mass (BM) was included as a strictly proportional linear effect interacted with all effects except blinding. Probabilistic inferences were derived with reference to thresholds for small and moderate effects on performance of 0.5% and 1.5%, respectively. Publication bias was reduced by excluding study estimates with a standard error >2.7%. The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly mod- erate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5mmoL/kg/BM (-0.3g/kgIBM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of l.SmmoL/kgIBM (-0.5gIkgJBM) had an unclear effect on performance of 0.0% (±1.3%), while the five studies and six estimates for ammonium chloride produced a possibly moderate impairment of 1.6% (±1.9%) with a typical dose of 5.5mmoL/kgIBM (-0.3glkg/BM). Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (± 1 .1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ± 1.2%. The only noteworthy effects involving physiological variables were a small correlation between performance and pre-exercise increase in blood bicarbonate with sodium bi- carbonate ingestion, and a very large correlation between the increase in blood bicarbonate and time between sodium citrate ingestion and exercise. The approximate equal and opposite effects of sodium bicarbonate and am- monium chloride are consistent with direct performance effects of pH, but sodium citrate appears to have some additional metabolic inhibitory effect. Important future research includes studies of sodium citrate ingestion several hours before exercise and quantification of gastrointestinal symptoms with sodium bicarbonate and citrate. Although individual responses may vary, we recommend ingestion of 0.3-0.5 glkg/BM sodium bicarbonate to improve mean power by 1.7% (±2.0%) in high-intensity races of short duration. ABSTRACT FROM AUTHOR

Effect of sodium bicarbonate on [HCO3 -], pH, and gastrointestinal symptoms

Context: Sodium bicarbonate (NaHCO3) is often ingested at a dose of 0.3 g/kg body mass (BM), but ingestion protocols are inconsistent in terms of using solution or capsules, ingestion period, combining NaHCO3 with sodium citrate (Na3C6H5O7), and coingested food and fluid. Purpose: To quantify the effect of ingesting 0.3 g/ kg NaHCO3 on blood pH, [HCO3 -], and gastrointestinal (GI) symptoms over the subsequent 3 hr using a range of ingestion protocols and, thus, to determine an optimal protocol. Methods: In a crossover design, 13 physically active subjects undertook 8 NaHCO3 experimental ingestion protocols and 1 placebo protocol. Capillary blood was taken every 30 min and analyzed for pH and [HCO3 -]. GI symptoms were quantified every 30 min via questionnaire. Statistics used were pairwise comparisons between protocols; differences were interpreted in relation to smallest worthwhile changes for each variable. A likelihood of >75% was a substantial change. Results: [HCO3 -] and pH were substantially greater than in placebo for all other ingestion protocols at almost all time points. When NaHCO3 was coingested with food, the greatest [HCO3 -] (30.9 mmol/kg) and pH (7.49) and lowest incidence of GI symptoms were observed. The greatest incidence of GI side effects was observed 90 min after ingestion of 0.3 g/kg NaHCO3 solution. Conclusions: The changes in pH and [HCO3 -] for the 8 NaHCO3-ingestion protocols were similar, so an optimal protocol cannot be recommended. However, the results suggest that NaHCO3 coingested with a high-carbohydrate meal should be taken 120-150 min before exercise to induce substantial blood alkalosis and reduce GI symptoms. ABSTRACT FROM AUTHOR

PLT practitioners : soldiers For “vocationalism”, or double agents?

This presentation extends on some previous work around my PhD research.
I question ways in which social structures are inscribed into legal education practices, and conversely, whether practices can modify those structures. I argue PLT practitioners are not simply soldiers for a “vocationalist” strategy. Instead, I re-imagine PLT practitioners as “double agents” or “resistance fighters”, lamplighters in a still emergent professional trajectory. It is a trajectory catalysed by the 1970s introduction of institutional PLT; just a baby really, in the context of English common law.

In Bourdieu’s terms it is possible, by revisiting past struggles in Australian legal education, to conceptualise institutional PLT as the product of judicial, professional, and academic struggles to produce a vocationalised, non-academic, and critique-free sub-field within the juridical field. Those struggles succeeded, to some extent, in the extra-individual dimension of structures, regulation, and institutions, to collectively inculcate preferred dispositions within individuals about legal education and professional identity.

That account, however, ignores the potential for agency and alterity – the ways in which individuals might appropriate, in Certeau’s terms, the resources of the legal field to explore new professional trajectories. For some, these trajectories involve struggles to enrich, and add texture to, legal education. Drawing on interviews with PLT practitioners, I identify multi-vocal and multi-perspectival themes, including notions of social justice, equality, professional ethics, personal improvement, and indeed, interest in scholarship of teaching and learning.

It is in this sense I re-imagine PLT practitioners as “double agents”, operating betwixt and between dominant domains in law. In my view, PLT practitioners can participate in conceptualising and developing emergent approaches in legal education, and to theorise “practice” as lawyers and educators. Scholarship of teaching and learning has its part to play in this. It provides a means, as lawyers and as educators, to discover information, to reflect, critique, communicate, and conceptualise, insights about “practice” and practices.

Differentiation of cultured epithelial cells : response to toxic agents

Cell culture systems are instrumental in elucidating regulation of normal function and mechanisms of its perturbation by toxic substances. To this end, three applications of epithelial cells cultured with 3T3 feeder layer support are described. First, treatment of the premalignant human epidermal keratinocyte line SCC-12F2 with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate suppressed cell growth and differentiation. This agent produced a biphasic growth response greatly inhibiting cell growth at 1 to 10 nM, but much less above 100 nM. Expression of the differentiated functions involucrin and transglutaminase was found to be inhibited markedly at concentrations above 10 nM. Second, 3-methylcholanthrene toxicity was surveyed in a variety of rat epithelial cell types. The two most sensitive to growth inhibition were epidermal and mammary epithelial cells, while those from bladder, prostate, thyroid, and endometrium were insensitive to growth inhibition. Great differences were evident even among those cells derived from stratified squamous epithelia (epidermal, esophageal, vaginal, forestomach) despite their expression of aryl hydrocarbon hydroxylase activities to similar degrees. Finally, expression of estrogen receptors in rat endometrial cells was shown to be stimulated by the cAMP-elevating agent forskolin. Maximal stimulation of 3- to 6-fold occurred in 6 hr, compatible with a requirement for protein synthesis. Although expressing keratinocyte character (transglutaminase activity and envelope forming ability), the cells thus retain some hormonal character that may be modulated by cAMP-dependent kinase activity. Pursuit of such results will aid in understanding differences in response among cell types and species, in elucidating mechanisms of action of known toxic substances and, ultimately, in predicting toxicity of less well understood agents.

Atypical antipsychotic agents; peas in a pod or chalk and cheese?

With escalating health expenditure and a shrinking purse, there is increased focus on the cost efficacy of still patented versus generic medications in general, and for atypical antipsychotics in particular. In a recent BMC Medicine article, Godman and colleagues presented data indicating poor uptake of the off patent atypical antipsychotic risperidone, arguing for authorities to mandate its greater use. This is under the assumption of clinical equivalence of atypical antipsychotics. This commentary argues that there are clinically meaningful differences between atypical antipsychotics and important inter-individual heterogeneity in clinical response and tolerability. Access to a broad range of atypical antipsychotics enables clinicians to tailor care, taking consideration of differential efficacy and adverse effects profile in order to meet the needs of individual patients with improved real world effectiveness of treatment. Restriction of agent choice risks detracting from optimal clinical care, with possible poorer outcomes and greater costs of care. A balance between encouraging use of cheapest in class agent and allowing access to various atypical agents for tailored care is likely to produce optimal health outcomes.Please see related article: http://www.biomedcentral.com/1741-7015/12/98.

Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression

Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression. Trial registration: Australian and New Zealand Clinical Trial Registry ACTRN12612000830897.

The influence of stocking rate and mixed grazing of Angora goats and Merino sheep on animal and pasture production in southern Australia. 4. Gastrointestinal parasitism

Gastrointestinal nematodes limit the growth, production and welfare of goats but there are few reliable sources of information for recommending management practices across flocks. The effects of animal species (Angora goat, Merino sheep, mixed-grazed goats and mixed-grazed sheep at the ratio of 1:1) and stocking rate (SR: 7.5, 10, 12.5 animals/ha) on gastrointestinal parasitism were determined in a replicated experiment on improved annual temperate pastures in southern Australia, from 1981 to 1984. Detailed monitoring of gastrointestinal nematodes was undertaken on animals before, during (five times per year) and at the conclusion of studies using faecal strongyle egg counts (WEC) and total worm counts. Sheep had a greater proportion of nematodes as Teladorsagia spp. and goats a greater incidence of Trichostrongylus spp. Both goats and sheep developed resistance to Nematodirus spp. during the experiment. WEC was similar in goats and sheep at the start of the experimental period but, thereafter, was consistently greater in goats than in sheep. While WEC was highly related to total worm count, the regressions for sheep and goats were different. Increasing the SR increased the WEC of goats and mixed-grazed goats but not of sheep. During the experiment, WEC declined at 7 and 10 animals/ha but increased at 12.5/ha. Mixed grazing with goats provided beneficial effects for sheep at all stocking rates, but the effects for goats were dependent on the stocking rate, being beneficial at 7.5 and 10/ha but harmful at 12.5/ha. The WEC of separately grazed goats were generally higher than the WEC of mixed grazed goats. The WEC of mixed sheep were lower than those of separately grazed sheep. During the experiment, the WEC of mixed grazed sheep declined faster than the WEC of separately grazed sheep but the WEC of separately grazed goats at 12.5/ha and of mixed grazed goats at 10 and 12.5/ha increased. Under the environmental and pastoral conditions examined, Angora wether goats should not be grazed at SR above those recommended for wether sheep. In the present study, the impact of gastrointestinal-nematode infections in goats was reduced at lower SR. Further, mixed grazing of Angora wether goats with wether sheep at or below the recommended SR resulted in reduced gastrointestinal parasitism for both sheep and goats, compared with monospecific grazing conditions. Goats did not represent a gastrointestinal-nematode hazard to sheep. © 2014 CSIRO.

Re-Imagining Practical Legal Training Practitioners – Soldiers for ‘Vocationalism’, or Double Agents?

I adopt a constructivist approach in order to study Australian PLT practitioners’ engagement with scholarship of teaching and learning (SoTL) in institutional practical legal training (PLT). Drawing on Bourdieu’s reflexive sociology and Certeau’s heterological science, I argue PLT is enclosed by discursive operations that constrain PLT practitioners’ engagement with SoTL. I contend SoTL could address a knowledge gap in practice research in law and legal education. I propose to re-imagine PLT teaching work by conceptualising it as an emergent professional trajectory, engaged in practice research, teaching and learning. By considering ways in which structures are inscribed into legal education practice, and conversely, whether practice can modify such structures, I re-imagine PLT practitioners as double agents or resistance fighters, enriching legal education through SoTL as practice research.

Mobile Agents Security Protocols

Mobile agents are expected to run in partially unknown and untrustworthy environments. They transport from one host to another host through insecure channels and may execute on non-trusted hosts. Thus, they are vulnerable to direct security attacks of intruders and non-trusted hosts. The security of information the agents collect is a fundamental requirement for a trusted implementation of electronic business applications and trade negotiations. This chapter discusses the security protocols presented in the literature that aim to secure the data mobile agents gather while searching the Internet, and identifies the security flaws revealed in the protocols. The protocols are analyzed with respect to the security properties, and the security flaws are identified. Two recent promising protocols that fulfill the various security properties are described. The chapter also introduces common notations used in describing security protocols and describes the security properties of the data that mobile agents gather.

A critical ethnography of communication processes involving the management of oral chemotherapeutic agents by patients with a primary diagnosis of colorectal cancer: study protocol.

AIM: To describe the protocol used to examine the processes of communication between health professionals, patients and informal carers during the management of oral chemotherapeutic medicines to identify factors that promote or inhibit medicine concordance. BACKGROUND: Ideally communication practices about oral medicines should incorporate shared decision-making, two-way dialogue and an equality of role between practitioner and patient. While there is evidence that healthcare professionals are adopting these concordant elements in general practice there are still some patients who have a passive role during consultations. Considering oral chemotherapeutic medications, there is a paucity of research about communication practices which is surprising given the high risk of toxicity associated with chemotherapy. DESIGN: A critical ethnographic design will be used, incorporating non-participant observations, individual semi-structured and focus-group interviews as several collecting methods. METHODS: Observations will be carried out on the interactions between healthcare professionals (physicians, nurses and pharmacists) and patients in the outpatient departments where prescriptions are explained and supplied and on follow-up consultations where treatment regimens are monitored. Interviews will be conducted with patients and their informal carers. Focus-groups will be carried out with healthcare professionals at the conclusion of the study. These several will be analysed using thematic analysis. This research is funded by the Department for Employment and Learning in Northern Ireland (Awarded February 2012). DISCUSSION: Dissemination of these findings will contribute to the understanding of issues involved when communicating with people about oral chemotherapy. It is anticipated that findings will inform education, practice and policy.

Novel 1,4-substituted-1,2,3-triazoles as antitubercular agents

Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising antitubercular activity with six possessing minimum inhibitory concentration (MIC) values <10 μg mL^-1, and total selectivity for Mycobacterium tuberculosis (Mtb) growth inhibition. A second set of 21 compounds bearing variations on ring C were synthesized and evaluated. This second library gave an additional six compounds displaying MIC values ≤10 μg mL^-1 and total selectivity for Mtb growth inhibition. These compounds serve as an excellent starting point for further development of antitubercular therapies.

Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents

Background Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. Objective To describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents. Design, setting, and participants We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. Outcome measurements and statistical analysis Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. Results and limitations The post-endocrine-therapy patients received abiraterone (n = 32), sequential abiraterone and enzalutamide (n = 5) or enzalutamide (n = 4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1-10 cycles) were delivered, with ≥50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n = 18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. Conclusions This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. Patient summary We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments. © 2013 European Association of Urology.