Ethics, Evidence Based Sports Medicine, and the Use of Platelet Rich Plasma in the English Premier League.

The use of platelet rich plasma (PRP) as a novel treatment is discussed in the context of a qualitative research study comprising 38 interviews with sports medicine practitioners and other stakeholders working within the English Premier League during the 2013-16 seasons. Analysis of the data produced several overarching themes: conservatism versus experimentalism in medical attitudes; therapy perspectives divergence; conflicting versions of appropriate evidence; subcultures; community beliefs/practices; and negotiation of medical decision-making. The contested evidence base for the efficacy of PRP is presented in the context of a broader professional shift towards evidence based medicine within sports medicine. Many of the participants while accepting this shift are still committed to casuistic practices where clinical judgment is flexible and does not recognize a context-free hierarchy of evidentiary standards to ethically justifiable practice. We also discuss a tendency in the data collected to consider the use of deceptive, placebo-like, practices among the clinician participants that challenge dominant understandings of informed consent in medical ethics. We conclude that the complex relation between evidence and ethics requires greater critical scrutiny for this emerging specialism within the medical community.

The effect of dietary energy:protein ratio, protein quality and food allocation on the efficiency of utilisation of protein by broiler chickens.

1. Various theories have been proposed to explain the reduced performance of broilers when given feeds excessively high in protein, but a satisfactory solution to this problem had, up to now, not been found. Three experiments were conducted to test the hypothesis that the efficiency of utilisation of protein (ep) is a linear-plateau function of the ratio between the feed apparent metabolisable energy and digestible crude protein contents (AMEn:DCP) and that dietary protein quality, feed allocation and sex do not influence this relationship. 2. A 'linear-plateau' model successfully described the efficiency of protein utilisation (ep) as a function of AMEn:DCP in all three experiments. In Experiment 1, with both sexes being both ad libitum and control fed, the breakpoint was at 58.6 MJ AMEn/kg DCP. In Experiment 2, both sexes were fed balanced and unbalanced protein series, and at different rates, the slopes of the ascending part of the linear-plateau relationships for the different treatments were the same for all treatments (0.0204), and the inflection point was at 71 MJ AMEn/kg DCP. Using similar treatments in Experiment 3, the breakpoint for the balanced protein was 72 MJ/kg and for the unbalanced, 64, with a combined slope of 68 MJ AMEn/kg DCP. 3. The three experiments provide adequate evidence that ep is a linear-plateau function of the dietary AMEn:DCP ratio with a breakpoint of around 66.2 ± 1.98 MJ AMEn/kg DCP. Below this critical ratio, food intake declines as does protein and lipid retention. 4. That broilers, like pigs, exhibit an energy-dependent phase when high-protein feeds are offered is of practical importance when formulating pre-starter feeds for broilers and starter feeds for turkey poults as the ep of such feeds may well fall below the maximum due to the lack of dietary energy required to process the high dietary protein contained in such feeds resulting in poorer performance than expected.

Balancing training and outcomes in total knee replacement: A ten-year review.

INTRODUCTION: 10-year study examining differences in total knee arthroplasty (TKA) functional outcomes and survivorship in patients operated on by consultant and trainee orthopaedic surgeons. METHOD: Data was prospectively collected from all elective TKAs performed at our three linked institutions. Patient demographics, surgeon grade, and length of hospital stay were recorded. Outcomes pre-operatively and at 1, 3, 5, 7 and 10 years included mortality, need for revision surgery and function as documented by the patients' Knee Society Score. RESULTS: 686 patients were included in the study. 450 (65.5%) patients were operated by consultant surgeons and 236 (34.4%) by trainees. On multivariate analysis no significant differences were observed between groups in length of hospital stay (p = 0.695), implant survival (p = 0.422), and function (p = 0.507) at 10 years. On Cox regression analysis no significant difference was observed in mortality (p = 0.209) at 10 years. 4 patients over this time period were lost to formal follow up. CONCLUSION: No significant difference was observed in the TKA outcomes between consultants and trainees 10 years post-operatively.

Do trainee surgeons have an adverse effect on the outcome after total hip arthroplasty?: a ten-year review.

AIMS: The long-term functional outcome of total hip arthroplasty (THA) performed by trainees is not known. A multicentre retrospective study of 879 THAs was undertaken to investigate any differences in outcome between those performed by trainee surgeons and consultants. PATIENTS AND METHODS: A total of 879 patients with a mean age of 69.5 years (37 to 94) were included in the study; 584 THAs (66.4%) were undertaken by consultants, 138 (15.7%) by junior trainees and 148 (16.8%) by senior trainees. Patients were scored using the Harris Hip Score (HHS) pre-operatively and at one, three, five, seven and ten years post-operatively. Surgical outcome, complications and survival were compared between groups. The effect of supervision was determined by comparing supervised and unsupervised trainees. A primary univariate analysis was used to select variables for inclusion in multivariate analysis. RESULTS: There was no evidence that the grade of the surgeon had a significant effect on the survival of the patients or the rate of revision (p = 0.987 and 0.405, respectively) up to 12 years post-operatively. There was no significant difference in post-operative functional HHS or total HHS among consultants, junior and seniors up to ten years post-operatively (p = 0.401 and 0.331), respectively. There was no significant difference in hospital stay (p = 0.855) between different grades of surgeons. There was no evidence that the level of supervision had an effect on the survival of the patients or the rate of revision (p = 0.837 and 0.203, respectively) up to 12 years post-operatively. There was no significant difference between supervised and unsupervised trainee groups in post-operative functional HHS or total HHS up to ten years post-operatively (p = 0.213 and 0.322, respectively). There was no significant difference in the mean hospital stay between supervised and unsupervised trainees (p = 0.908). TAKE HOME MESSAGE: This study suggests that when trainees are appropriately supervised, they can obtain results comparable with those of their consultant colleagues when performing THA.

Technology identity: the role of sociotechnical representations in the adoption of medical devices.

This study explored the sociotechnical influences shaping the naturally-occurring adoption and non-adoption of device technologies in the UK's National Health Service (NHS), amid increasing policy interest in this area. The study was informed by Science and Technology Studies and structuration and Actor Network Theory perspectives, drawing attention to the performative capacities of the technology alongside human agentic forces such as agendas and expectations, in the context of structural and macro conditions. Eight technologies were studied using a comparative ethnographic case study design and purposive and snowball sampling to identify relevant NHS, academic and industry participants. Data were collected between May 2009 and February 2012, included in-depth interviews, conference observations and printed and web-based documents and were analysed using constructivist grounded theory methods. The study suggests that while adoption decisions are made within the jurisdiction of healthcare organisations, they are shaped within a dynamic and fluid 'adoption space' that transcends organisational and geographic boundaries. Diverse influences from the industry, health care organisation and practice, health technology assessment and policy interact to produce 'technology identities.' Technology identities are composite and contested attributes that encompass different aspects of the technology (novelty, effectiveness, utility, risks, requirements) and that give a distinctive character to each. We argue that it is these socially constructed and contingent heuristic identities that shape the desirability, acceptability, feasibility and adoptability of each technology, a perspective that policy must acknowledge in seeking to intervene in health care technology adoption.

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology.

Regenerative medicine holds great promise as a way of addressing the limitations of current treatments of ischaemic disease. In preclinical models, transplantation of different types of stem cells or progenitor cells results in improved recovery from ischaemia. Furthermore, experimental studies indicate that cell therapy influences a spectrum of processes, including neovascularization and cardiomyogenesis as well as inflammation, apoptosis and interstitial fibrosis. Thus, distinct strategies might be required for specific regenerative needs. Nonetheless, clinical studies have so far investigated a relatively small number of options, focusing mainly on the use of bone marrow-derived cells. Rapid clinical translation resulted in a number of small clinical trials that do not have sufficient power to address the therapeutic potential of the new approach. Moreover, full exploitation has been hindered so far by the absence of a solid theoretical framework and inadequate development plans. This article reviews the current knowledge on cell therapy and proposes a model theory for interpretation of experimental and clinical outcomes from a pharmacological perspective. Eventually, with an increased association between cell therapy and traditional pharmacotherapy, we will soon need to adopt a unified theory for understanding how the two practices additively interact for a patient's benefit.

WITHDRAWN: Non-aspirin, non-steroidal anti-inflammatory drugs for treating osteoarthritis of the knee.

BACKGROUND: Osteoarthritis(OA) is the most common rheumatic disease. Simple analgesics are now accepted as the appropriate first line pharmacological treatment of uncomplicated OA. Non-aspirin NSAIDs are licensed for the relief of pain and inflammation arising from rheumatic disease. OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last performed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading "osteoarthritis" was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac versus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences between treatments. In one study [Bellamy 1993], a statistically significant difference was detected between treatments with regard to withdrawals due to lack of efficacy. In this trial, which compared equivalent NSAID doses, diclofenac was the favoured NSAID compared to tenoxicam(p=0.04). Two studies showed a statistical difference in patient global assessment of condition, which favoured the trial NSAID. In both cases the trial NSAID was etodolac, used in doses approximately 25-44% greater than the reference NSAID. Two studies showed a statistically significant difference in pain relief between NSAIDs. The trial NSAID in both cases was again etodolac but the doses exceeded those of the reference NSAIDs. AUTHORS' CONCLUSIONS: In spite of the large number of publications in this area, there are few randomized controlled trials. Furthermore, most trials comparing two or more NSAIDs suffer from substantial design errors. From the results of this review it is concluded that no substantial evidence is available related to efficacy, to distinguish between equivalent recommended doses of NSAIDs. Had studies employed appropriate doses of comparator drug, most would have been sufficiently powerful to detect clinically important differences in efficacy. As differences in efficacy between NSAIDs have not been recorded, the selection of an NSAID for prescription for OA knee should be based upon relative safety, patient acceptability and cost.

Feeding patterns in a small-bodied nocturnal folivore (Avahi laniger) and the influence of leaf chemistry: a preliminary study.

We present data on feeding patterns in Avahi laniger and compare these data to temporal variations in leaf chemistry. Because A. laniger is one of the smallest folivorous primates and has a monogastric stomach, we hypothesized that this lemur would display behavioural adaptations to a leaf-based diet by scheduling feeding times when leaves were of highest quality. Data were collected from May to August 2004 at the Vatoharanana site in Ranomafana National Park, Madagascar. A. laniger fed during different time periods despite leaf carbohydrate and protein concentrations exhibiting little variation throughout the night. Although tannin concentrations exhibited temporal fluctuations, they did not covary with A. laniger feeding times. We suggest that A. laniger feeding times cannot be explained entirely by variations in leaf chemistry.

Transient radio bursts from rotating neutron stars.

The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorter timescales. We found eleven objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 min to 3 h with radio emission typically detectable for <1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4-7 s for ten of the eleven sources, suggesting origins in rotating neutron stars. Despite the small number of sources detected at present, their ephemeral nature implies a total Galactic population significantly exceeding that of the regularly pulsing radio pulsars. Five of the ten sources have periods >4 s, and the rate of change of the pulse period has been measured for three of them; for one source, we have inferred a high magnetic field strength of 5 x 10(13) G. This suggests that the new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.

Novel (2E,4E,6Z)-7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic acid retinoid X receptor modulators are active in models of type 2 diabetes.

Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.

Effective communication in health care: exploring the skills of the teachers.

Following the growing commitment to teach communication skills in health care, a project was designed to identify a group of Health Professionals with a responsibility for teaching communication skills in Health Care. This group would have their communication skills assessed, using positive feedback, and attend workshops to improve both their communication and teaching skills. Four key tutors were recruited to the study and were each asked to identify a further three tutors, in their own geographical area, to form a "cell". This sample of 16 tutors remained constant throughout the study. Skills were monitored by the assessment of audio-taped interviews, one made prior to the first workshop and two others at agreed intervals. Written feedback was given on the first interview, plus the option of verbal feedback on a skills study day. Written feedback was given on subsequent interviews. Changes in skills were monitored and baseline skills compared to previous skills training. The results show, with two exceptions, that there appears to be a link between baseline skills and previous training in communication skills. For three "cells", there are gains in overall scores from first to third interview, but for the fourth "cell", which had high baseline scores, there was only minimal change. The work suggests, that for those who teach Communication in Health Care, training is a pre-requisite. Further work is required in this area.

Effects of the number of channels and speech-to-noise ratio on rate of connected discourse tracking through a simulated cochlear implant speech processor.

OBJECTIVE: To investigate the effects of number of channels and speech-to-noise ratio on connected discourse tracking (CDT) through simulations of cochlear implant speech processing. Previous studies have used citation-form vowel and consonant materials or simple sentences. CDT rates were expected to be less likely to be limited by ceiling effects and more representative of everyday speech communication. DESIGN: Four normal-hearing subjects were presented with speech processed through a real-time sine-excited vocoder having three, four, eight, or 12 channels. Amplitude envelopes extracted from each band modulated sinusoidal carrier signals placed at each band center frequency. Speech-spectrum shaped noise was added to speech before vocoder processing at three signal to noise ratios based on real-time measurements of speech level (+7, +12, +17 dB). RESULTS: CDT rates increased significantly with number of channels up to eight in both quiet and noise, and decreased significantly with each increase in noise level from quiet. CONCLUSIONS: The effects on CDT rates of the number of channels and speech-to-noise ratio are highly correlated with intelligibility measures for Hearing in Noise Test (HINT) sentences, consonants and vowels. However, HINT sentence scores even in noise show ceiling effects that obscure the advantages of processors with eight or more channels. Moderate levels of noise that have only slight effects on other measures significantly affected CDT rate. CDT rates with three or four bands of spectral information were much lower than asymptotic rates, especially in the presence of noise.

Innovation and regulation in human implant technologies: developing comparative approaches.

Human implant technologies are subject to continual innovation and proliferation, raising important issues for technology testing, healthcare sciences, clinical performance and risk assessment, and regulation. The regulatory environment of medical devices is being shaped by harmonisation of standards in the European Union. The aim of this paper is to compare the histories and current regulatory environment of two technologies, breast implants and artificial hips, and to consider the implications of this comparison for a sociological healthcare research agenda to investigate the issues raised. The main focus is upon developments in the United Kingdom. Major points of contrast between the two technologies include the institutional contexts in which clinical evidence has been marshalled for government attention; the relative importance of strategic alliances between clinicians and manufacturers in the innovation process; the degree of public controversy evident; the varying definitions of an 'adverse incident' within medical device vigilance systems; and in the UK the presence of a national register for breast implants but not for hip implants. Inter-national contrasts in these dimensions are noted. The analysis suggests that improved understanding is required of the institutional, organisational and professional processes involved in implant technology innovation and regulation. A comparative research agenda is proposed, focusing upon: innovativeness and proliferation; safety and technological standards; clinical and social outcomes; and consumer/user information and choice. It is concluded that research in these areas will enhance the 'evidence-base' for the evaluation of human implant technologies in the context of their innovatory and regulatory environments.

Effects of the salience of pitch and periodicity information on the intelligibility of four-channel vocoded speech: implications for cochlear implants.

Recent simulations of continuous interleaved sampling (CIS) cochlear implant speech processors have used acoustic stimulation that provides only weak cues to pitch, periodicity, and aperiodicity, although these are regarded as important perceptual factors of speech. Four-channel vocoders simulating CIS processors have been constructed, in which the salience of speech-derived periodicity and pitch information was manipulated. The highest salience of pitch and periodicity was provided by an explicit encoding, using a pulse carrier following fundamental frequency for voiced speech, and a noise carrier during voiceless speech. Other processors included noise-excited vocoders with envelope cutoff frequencies of 32 and 400 Hz. The use of a pulse carrier following fundamental frequency gave substantially higher performance in identification of frequency glides than did vocoders using envelope-modulated noise carriers. The perception of consonant voicing information was improved by processors that preserved periodicity, and connected discourse tracking rates were slightly faster with noise carriers modulated by envelopes with a cutoff frequency of 400 Hz compared to 32 Hz. However, consonant and vowel identification, sentence intelligibility, and connected discourse tracking rates were generally similar through all of the processors. For these speech tasks, pitch and periodicity beyond the weak information available from 400 Hz envelope-modulated noise did not contribute substantially to performance.

A selective peroxisome proliferator-activated receptor-gamma (PPARgamma) modulator blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists such as the thiazolidinediones are insulin sensitizers used in the treatment of type 2 diabetes. These compounds induce adipogenesis in cell culture models and increase weight gain in rodents and humans. We have identified a novel PPARgamma ligand, LG100641, that does not activate PPARgamma but selectively and competitively blocks thiazolidinedione-induced PPARgamma activation and adipocyte conversion. It also antagonizes target gene activation as well as repression in agonist-treated 3T3-L1 adipocytes. This novel PPARgamma antagonist does not block adipocyte differentiation induced by a ligand for the retinoid X receptor (RXR), the heterodimeric partner for PPARgamma, or by a differentiation cocktail containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Surprisingly, LG100641, like the PPARgamma agonist rosiglitazone, increases glucose uptake in 3T3-L1 adipocytes. Such selective PPARgamma antagonists may help determine whether insulin sensitization by thiazolidinediones is mediated solely through PPARgamma activation, and whether there are PPARgamma-ligand-independent pathways for adipocyte differentiation. If selective PPARgamma modulators block adipogenesis in vivo, they may prevent obesity, lower insulin resistance, and delay the onset of type 2 diabetes.

Non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the knee.

OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last perfomed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading osteoarthritis was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac vesus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences betw

Contributions of temporal encodings of voicing, voicelessness, fundamental frequency, and amplitude variation to audio-visual and auditory speech perception.

Auditory and audio-visual speech perception was investigated using auditory signals of invariant spectral envelope that temporally encoded the presence of voiced and voiceless excitation, variations in amplitude envelope and F0. In experiment 1, the contribution of the timing of voicing was compared in consonant identification to the additional effects of variations in F0 and the amplitude of voiced speech. In audio-visual conditions only, amplitude variation slightly increased accuracy globally and for manner features. F0 variation slightly increased overall accuracy and manner perception in auditory and audio-visual conditions. Experiment 2 examined consonant information derived from the presence and amplitude variation of voiceless speech in addition to that from voicing, F0, and voiced speech amplitude. Binary indication of voiceless excitation improved accuracy overall and for voicing and manner. The amplitude variation of voiceless speech produced only a small increment in place of articulation scores. A final experiment examined audio-visual sentence perception using encodings of voiceless excitation and amplitude variation added to a signal representing voicing and F0. There was a contribution of amplitude variation to sentence perception, but not of voiceless excitation. The timing of voiced and voiceless excitation appears to be the major temporal cues to consonant identity.

Changes in plasma and milk concentrations of glucose and IGF-1 in response to exogenous growth hormone in lactating goats.

Exogenous growth hormone was administered subcutaneously to five lactating goats during the post-peak period of lactation. Milk yields increased significantly by approximately 20% in response to growth hormone. Blood and milk samples were taken in the periods before, during and after growth hormone treatment. The concentrations of glucose in milk increased significantly by approximately 50% in the period following growth hormone treatment at a time corresponding to the increase in milk yield. There was a transient increase in plasma glucose concentrations immediately following growth hormone treatment before either milk glucose concentrations or milk yields were increased. Both free and total IGF-1 concentrations in plasma increased slowly following growth hormone treatment. The increase in plasma IGF-1 corresponded to the increase in milk yields and milk glucose concentrations. Concentrations of IGF-1 in milk increased more rapidly than those in plasma, rising by approximately 150% following growth hormone treatment, and were starting to decline by the time that milk yield and milk glucose concentrations were at their maximum. As milk glucose concentrations have been shown previously to reflect changes in the intracellular concentration of glucose, the results indicate that part of the mechanism by which growth hormone stimulates milk production is by increasing the intracellular availability of glucose for lactose synthesis. The results also suggest that changes occur in the concentrations of IGF-1 in the environment of the mammary gland before changes are observed in the general circulation, and that these are reflected in the changed concentrations in milk.