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The contemporary approach to pain measurement in people and animals seeks to measure the affective (emotional) component of the pain experience using structured questionnaires with formal scoring methodology. Chronic pain has wide-ranging impacts which affects the quality of life (QOL) of the individual, whether that is a person or an animal. Accordingly instruments to measure chronic pain are designed to measure its impact on QOL and are called health-related quality of life (HRQL) instruments. In veterinary science instruments to measure pain are based on behavioural observation by the veterinary surgeon/nurse in the case of acute pain and by the owner in the case of chronic pain. The development of HRQL instruments is an expanding field in veterinary science, not just for the measurement of pain, but for other chronic diseases, and it has a wide application in pharmaceutical research and clinical practice to improve patient care. This review highlights the challenges involved in creating such measures for dogs and cats, seeking to provide the reader with an understanding of their development process. It then provides an overview of the current status with regard to acute and chronic pain measurement.

Augmentation of cyclic nucleotide signaling through inhibition of phosphodiesterase (PDE) activity has long been understood to enhance memory. Efforts in this domain have focused predominantly on PDE4, a cAMP-specific phosphodiesterase implicated in consolidation. But less is known about the function of other PDEs expressed in neuroanatomical regions critical to memory. The PDE1 isoforms are the only PDEs to regulate neuronal cAMP and cGMP levels in a Ca2+/Calmodulin (CaM) dependent manner. Here, we show that knock-down of PDE1B in hippocampus of adult mice enhances contextual and spatial memory without effect on non-cognitive behaviors. Pharmacological augmentation of memory in rats was observed with a selective inhibitor of PDE1 dosed before and immediately after training, but not with drug dosed either 1 h after training or before recall. Our data clearly demonstrate a role for the PDE1B isoforms as negative regulators of memory, and they implicate PDE1 in an early phase of consolidation, but not retrieval. Inhibition of PDE1B is a promising therapeutic mechanism for treating memory impairment.

As regards authors Linda Altieri and Fedele Greco, the research work underlying this paper was partially funded by an FIRB 2012 [grant number RBFR12URQJ]; title: Statistical modelling of environmental phenomena: pollution, meteorology, health and their interactions) for research projects by the Italian Ministry of Education, Universities and Research. This work presents advanced computational aspects of a new method for changepoint detection on spatio-temporal point process data. We summarize the methodology, based on building a Bayesian hierarchical model for the data and declaring prior conjectures on the number and positions of the changepoints, and show how to take decisions regarding the acceptance of potential changepoints. The focus of this work is about choosing an approach that detects the correct changepoint and delivers smooth reliable estimates in a feasible computational time; we propose Bayesian P-splines as a suitable tool for managing spatial variation, both under a computational and a model fitting performance perspective. The main computational challenges are outlined and a solution involving parallel computing in R is proposed and tested on a simulation study. An application is also presented on a data set of seismic events in Italy over the last 20 years. Postprint

This study reports an inter-laboratory comparison of the 3He and 4He concentrations measured in the pyroxene material CRONUS-P. This forms part of the CRONUS-Earth and CRONUS-EU programs, which also produced a series of natural reference materials for in situ produced ^(26)Al, ^(10)Be, ^(14)C, ^(21)Ne and ^(36)Cl. Six laboratories (GFZ Potsdam, Caltech Pasadena, CRPG Nancy, SUERC Glasgow, BGC Berkeley, Lamont New York) participated in this intercomparison experiment, analyzing between 5 and 22 aliquots each. Intra-laboratory results yield ^3He concentrations that are consistent with the reported analytical uncertainties, which suggests that ^3He is homogeneous within CRONUS-P. The inter-laboratory dataset (66 determinations from the 6 different labs) is characterized by a global weighted mean of (5.02 ± 0.12) × 10^9 at g^(−1) with an overdispersion of 5.6% (2σ). ^4He is characterized by a larger variability than ^3He, and by an inter-lab global weighted mean of (3.60 ± 0.18) × 10^(13) at g^(−1) (2σ) with an overdispersion of 10.4% (2σ). There are, however, some systematic differences between the six laboratories. More precisely, 2 laboratories obtained mean ^3He concentrations that are about 6% higher than the clustered other 4 laboratories. This systematic bias is larger than the analytical uncertainty and not related to the CRONUS-P material (see Schaefer et al., 2015). Reasons for these inter-laboratory offsets are difficult to identify but are discussed below. To improve the precision of cosmogenic ^3He dating, we suggest that future studies presenting cosmogenic 3He results also report the ^3He concentration measured in the CRONUS-P material in the lab(s) used in a given study.

Initial work in Drosophila and mice demonstrated that the transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) is a master control gene for memory formation. The relationship between CREB and memory has also been found to be true in other species, including aplysia and rats. It is thus well-established that CREB activation plays a central role in memory enhancement and that CREB is activated during memory formation. On the basis of these findings, a phenotypic high-throughput screening campaign utilizing a CRE-luciferase (CRE-Luci) SK-N-MC cell line was performed to identify compounds that enhance transcriptional activation of the CRE promoter with a suboptimal dose of forskolin. A number of small-molecule hits of unknown mechanisms of action were identified in the screening campaign, including HT-0411. Follow-up studies suggested that the CREB activation by HT-0411 is attributed to its specific and selective inhibition of monoamine oxidase B (MAO-B). Further, HT-0411 was shown to improve 24 h memory in rodents in a contextual fear conditioning model. This report describes the lead optimization of a series of 5-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl) thiophene-2-carboxamides that were identified as novel, potent, and selective inhibitors of MAO-B. Extensive SAR studies and in vivo behavioral evaluations of this and other related analogue series identified a number of potential clinical development candidates; ultimately, compound 8f was identified as a candidate molecule with high selectivity toward MAO-B (29-56 nM) over MAO-A (19% inhibition at a screening concentration of 50 μM), an excellent profile against a panel of other enzymes and receptors, good pharmacokinetic properties in rodents and dogs, and efficacy in multiple rodent memory models.

OBJECTIVES To develop a composite measure pain scale tool to assess acute pain in cats and derive an intervention score. METHODS To develop the prototype composite measure pain scale-feline, words describing painful cats were collected, grouped into behavioural categories and ranked. To assess prototype validity two observers independently assigned composite measure pain scale-feline and numerical rating scale scores to 25 hospitalised cats before and after analgesic treatment. Following interim analysis the prototype was revised (revised composite measure pain scale-feline). To determine intervention score, two observers independently assigned revised composite measure pain scale-feline and numerical rating scale scores to 116 cats. A further observer, a veterinarian, stated whether analgesia was necessary. RESULTS Mean ± sd decrease in revised composite measure pain scale-feline and numerical rating scale scores following analgesia were 2 · 4 ± 2 · 87 and 1 · 9 ± 2 · 34, respectively (95% confidence interval for mean change in revised composite measure pain scale-feline between 1 · 21 and 3 · 6). Changes in revised composite measure pain scale-feline and numerical rating scale were significantly correlated (r = 0 · 8) (P < 0001). Intervention level score of ≥4/16 was derived for revised composite measure pain scale-feline (26 · 7% misclassification) and ≥3/10 for numerical rating scale (14 · 5% misclassification). CLINICAL SIGNIFICANCE A valid instrument with a recommended analgesic intervention level has been developed to assess acute clinical pain in cats that should be readily applicable in practice.

Aging is associated with declines in memory and cognitive function. Here, we evaluate the effects of HT-0712 on memory formation and on cAMP response element-binding protein (CREB)-regulated genes in aged mice. HT-0712 enhanced long-term memory formation in normal young mice at brain concentrations similar to those found to increase CRE-mediated gene expression in hippocampal neurons. Aged mice showed significantly poorer contextual and trace conditioning compared with young–adult mice. In aged mice, a single injection of HT-0712 significantly boosted contextual and trace long-term memory. Additional effects of HT-0712 were seen in a spatial memory task. Our parallel biochemical experiments revealed that inductions of the CREB-regulated genes, cFos, Zif268, and Bdnf, after fear conditioning were diminished in aged mice. HT-0712 facilitated expression of these CREB-regulated genes in aged hippocampus, indicating that the drug engages a CREB-regulated mechanism in vivo. These findings corroborate and extend our previous results on the mechanism of action of HT-0712 and its efficacy to enhance memory formation. Our data also indicate that HT-0712 may be effective to treat age-associated memory impairment in humans.

The usefulness of a pain assessment instrument is enhanced in general practice if the score can be linked to an intervention level, which is informative as to whether or not an animal requires analgesic treatment. Previously the authors described the derivation of an intervention level for the Glasgow Composite Measure Pain Scale (CMPS) short form tool for assessing acute pain in dogs (Reid and others 2007). More recently, the authors reported the validation of a behaviour-based tool (the revised composite measure pain scale (rCMPS)-F) for the assessment of acute pain in cats that was developed using psychometric principles (Calvo and others 2014). It takes the form of a structured questionnaire completed by an observer following a standard protocol and includes assessment of spontaneous and evoked behaviours, interactions with the animal and clinical observations. Construction and clinical testing of the tool supported its validity and provided some evidence for responsiveness, but sensitivity was moderate (misclassification, 26.7 per cent). In order to improve the performance of the tool, a simple three-point facial scale, which in preliminary testing had performed very well in classifying cats in pain, was developed (Holden and others 2014) with the intention of embedding it within the behaviour-based cat tool, an approach adopted previously in paediatric medicine (CRIES (Krechel and others 1995); Premature Infant Pain Profile (Stevens and others 1996)). This communication describes a single, multicentre …

Obesity is thought to affect quality of life, but limited objective data exist to support this supposition. The current study aim was to use a questionnaire to determine health-related quality of life (HRQOL) both before and after weight loss, in obese client-owned dogs. Fifty obese dogs were included, and represented a variety of breeds and genders. Prior to weight loss, owners were asked to complete a validated standardised questionnaire to determine HRQOL. Thirty of the dogs successfully completed their weight loss programme and reached target, and owners then completed a follow-up questionnaire. The completed questionnaire responses were transformed to scores corresponding to each of four factors (vitality, emotional disturbance, anxiety and pain), and scored on a scale of 0–6. Changes in the scores were used to explore the sensitivity of the questionnaire, and scores were correlated with responses to direct questions about quality of life and pain, as well as weight loss. Dogs that failed to complete their weight loss programme had lower vitality and higher emotional disturbance scores than those successfully losing weight (P = 0.03 for both). In the 30 dogs that completed, weight loss led to an increased vitality score (P < 0.001), and decreased scores for both emotional disturbance (P < 0.001) and pain (P < 0.001). However, there was no change in anxiety (P = 0.09). The change in vitality score was positively associated with percentage weight loss (rP = 0.43, P = 0.02) and percentage body fat loss (rP = 0.39, P = 0.03). These results indicate demonstrable improvement in HRQOL for obese dogs that successfully lose weight.

The use of corneocytes in suspension as a medium for the study of the effect of antifungal drugs on Trichophyton mentagrophytes arthroconidia was investigated. In the presence of clotrimazole or griseofulvin, arthroconidia germination in a suspension of corneocytes and in Sabouraud glucose liquid medium was significantly reduced compared with germination in drug-free media. Where antifungals were added to arthroconidia after an activation period during which germination occurred, any further germination was inhibited. The data showed that the growth of T. mentagrophytes in the presence of corneocytes offered a simple, rapid, inexpensive and relevant model for the assessment of antifungal activity of compounds for the treatment of dermatophytosis.

Summary: A clinical and mycological evaluation of the effectiveness of bifonazole gel was undertaken in general practice, the preparation being applied once daily for either 2 or 3 weeks with a final assessment at 4 weeks. There were 38 mycologically proven cases of tinea infection, 25 of tinea pedis and 13 of tinea cruris. A further 82 clinical cases were included to assess the acceptability of the gel, but were not included in the analysis of the results. After treatment, all signs and symptoms resolved in 60% of tinea pedis and 46% of tinea cruris infections (p < 0.01). Trichophyton rubrum was the commonest infecting organism (22 cases, 61%), followed by Trichophyton mentagrophytes var. interdigitale and Epidermophyton floccosum (7 cases each, 18% each). T. verrucosum and Microsporum canis were isolated from one case each respectively. Of 32 patients, where repeat examinations were undertaken, 10 (31%) were still positive at day 14, but only 2 (7%) at day 28, representing a mycological cure rate of 91%. There were no side-effects of any importance and, aesthetically, the gel preparation was highly acceptable to the patients. Zusammenfassung: Es wurde eine klinische und mykologische Bewertung der Wirkung von Bifonazol-Gel in der Allgemeinpraxis vorgenommen. Das Praparat wurde einmal taglich uber 2 oder 3 Wochen angewendet; die endgultige Bewertung wurde 4 Wochen nach Behandlungsbeginn vorgenommen. In die Studie gingen 38 Falle nachgewiesener Dermatophytosen-Infektionen ein, 25 davon betrafen Tinea pedis und 13 Tinea cruris. Weitere 82 klinische Falle wurden in die Bewertung der Gel-Akzeptanz, nicht jedoch klinisch und mykologisch bewertet. Nach der Behandlung waren 60% der Tinea pedis- und 46% der Tinea cruris-Infektionen klinisch geheilt (p < 0.01). Trichophyton rubrum war der haufigste Erreger (22 Falle, 61%), gefolgt von Trichophyton mentagrophytes var. interdigitale und Epidermophyton floccosum (je 7 Falle, je 18%). T. verrucosum und Microsporum canis wurden je einmal angezuchtet. Bei 32 Patienten wurden Wiederholungsuntersuchungen unternommen; davon waren 10 (31%) am 14. Tag noch positiv, aber nur 2 (7%) am 28. Tag, was einer Heilungsrate von 91% entspricht. Nebenwirkungen wurden nicht beobachtet. Das Gel wurde gut von den Patienten angenommen.

This research was supported by a University of Glasgow Faculty Scholarship to KMD, a Collaborative Gearing Scheme grant from the Natural Environmental Research Council and the British Antarctic Survey (CGS-77) and an ASSEMBLE infrastructure access grant to DMB. Baited underwater cameras are becoming a popular tool to monitor fish and invertebrate populations within protected and inshore environments where trawl surveys are unsuitable. Modelling the arrival times of deep-sea grenadiers using an inverse square relationship has enabled abundance estimates, comparable to those from bottom trawl surveys, to be gathered from deep-sea baited camera surveys. Baited underwater camera systems in the shallow water environments are however, currently limited to relative comparisons of assemblages based on simple metrics such as MaxN (maximum number of fish seen at any one time). This study describes a stochastic simulation approach used to model the behaviour of fish and invertebrates around a BUC system to enable absolute abundance estimates to be generated from arrival patterns. Species-specific models were developed for the tropical reef fishes the black tip grouper (Epinephelus fasciatus) and moray eel (Gymnothorax spp.) and the Antarctic scavengers; the asteroid (Odontaster validus) and the nemertean worm (Parbolasia corrugatus). A sensitivity analysis explored the impact of input parameters on the arrival patterns (MaxN, time to the arrival of the first individual and the time to reach MaxN) for each species generated by the model. Sensitivity analysis showed a particularly strong link between MaxN and abundance indicating that this model could be used to generate absolute abundances from existing or future MaxN data. It in effect allows the slope of the MaxN vs. abundance relationship to be estimated. Arrival patterns generated by each model were used to estimate population abundance for the focal species and these estimates were compared to data from underwater visual census transects. Using a Bland-Altman analysis, baited underwater camera data processed using this model were shown to generate absolute abundance estimates that were comparable to underwater visual census data. Postprint

Objective To assess the frequency of community pharmacists' advice-giving to women and to determine pharmacists' attitudes and perceived knowledge, confidence and embarrassment in providing such advice. Method A postal questionnaire was sent to a random sample of 600 Northern Ireland community pharmacists for self-completion. One reminder was sent. The questionnaire asked pharmacists to rate their knowledge on a list of women's health topics and to rate their confidence in dealing with women's health issues. Pharmacists were asked what actions they took to increase women's comfort in discussing potentially sensitive topics. They were also asked about the availability of women's health services locally. Closed response data were entered into SPSS for analysis while open question responses were collated and analysed separately. Key findings Pharmacy customers were predominantly female and the majority of pharmacists reported providing advice on women's health on a daily basis. Most pharmacists reported being confident and knowledgeable on women's health issues. Pharmacists had strategies to ensure that women felt comfortable discussing personal problems and they were not embarrassed dealing with such problems. Respondents felt more comfortable responding to, rather than initiating, such discussions. Personal views made it difficult for some respondents to provide advice on emergency contraception. Male pharmacists considered themselves to be less confident, less knowledgeable, more embarrassed and to have greater difficulty initiating a conversation on sensitive issues compared with female pharmacists. Conclusion Pharmacists on the whole were confident when dealing with requests for advice. Counselling confidence was related to counselling frequency. Initiation of conversations on women's health issues was difficult for some pharmacists. More active collaboration with the providers of other professional services available to women may enhance pharmacists' overall service provision for women customers.

This study traces the development of financial reporting in two publicly funded hospitals in New South Wales over the period 1857 to post‐1975, with particular focus on the use of cash and accrual accounting. The historical analysis draws on process and contextual change and stakeholder theory, and uses both primary and secondary data, to describe patterns of change (and non‐change) in the hospitals’ financial reporting and to identify the social and political influences associated with such reporting. The study provides historical context for recent developments in public sector reporting and accountability in Australia, particularly the (re)introduction of accrual accounting, and provides insights into the nature of accounting change both in public sector organizations and generally.

Kauri wood, a sub-fossil wood from New Zealand (which had previously been used in an IAEA exercise, IAEA-C4, in 1990), was considered to be an important sample to include in FIRI because it provided a link to previous exercises, was available in sufficient quantity, and was a “close to background” organic sample. IAEA-C4 had previously been criticized since it was believed that in its milling, some contamination had been introduced, so that a replacement sample would prove useful. The Kauri wood has a very low 14C activity and, as such, is very sensitive to even small amounts of contaminant carbon. Such low-activity samples give a true test for the laboratory procedures since pretreatment and laboratory background definition become critical.

TIRI was officially launched at the 14th International Radiocarbon Conference in Arizona in 1991. Prior to the conference, 150 laboratories received a letter describing the general intention to organize an intercomparison and over 90 laboratories from around the world responded positively to the invitation to participate. Simply stated, the aims of this intercomparison were: 1.To function as the third arm of the quality assurance (QA) procedure.2.To provide an objective measure of the maintenance and improvement in analytical quality.3.To assist in the development of a “self-help” scheme for participating laboratories.

The sets of core samples were distributed to over 120 laboratories that had returned an original questionnaire seeking expressions of interest in participation. A reporting format for the results was also agreed and distributed to the laboratories at the same time. This is shown in Table 2.1. Laboratories were originally given 1 yr (i.e., to August 2000) to complete the analyses and return the results, but this was later extended to December 2000. In this section, we briefly describe the laboratory characteristics and the overall response rate of the participating laboratories.

A significant and substantial effort has been made by the 14C community in quality assurance (QA) procedures, of which participation in FIRI is only one part but one that provides an independent and blind check on laboratory performance. The overwhelming willingness to participate is a testament to the importance which laboratories place on quality.

The design of FIRI included 3 pairs of duplicate samples: A and B (Kauri wood) near background, D and F (Belfast wood) around 50 pMC, and G and J (barley mash) at 111 pMC. Why include duplicates? Duplicates by their nature allow us to explore the within-lab variability and to assess whether the quoted errors are representative. We can also explore the differences as a function of the sample activity. In this section, we explore the differences between the duplicates. We also consider some different graphical presentations. First, we summarize the differences, then graphically explore the boxplot (to consider the distribution of differences), then a scatterplot of the duplicate pair (to show correlation and reproducibility), and finally, a measure of agreement plot (Bland and Altman 1999). The horizontal axis in this final plot is the mean of the duplicate pair and the vertical axis is the difference in the duplicate pair. Agreement between the pairs would result in the points being randomly scattered around the horizontal zero line.

Radiocarbon dating is universally used as an essential dating tool in the archaeological and earth (Quaternary) sciences. The technique has enjoyed considerable success with ongoing developments in both the sophistication of experimental practice and an ever-widening range of applications. Most recently (since the 1980s), a new generation of laboratories has been created, based on the exploitation of accelerator mass spectrometry (AMS) for the differentiation and measurement of carbon isotope abundances in natural materials. Worldwide, there are over 100 14C laboratories now operational in universities, research organizations, museums, and as commercial enterprises. There is an inevitable diversity of experimental approaches and applied priorities within these facilities. Some are well established, while others are relatively recent members of the international 14C community. Consequently, as a group, the laboratories reflect to varying extents the progress achieved over several decades of experience and methodological options. Furthermore, since progress in archaeology and related earth sciences cannot respect geographical and/or present political boundaries, there has been, and continues to be, an inevitable consequence that sample materials from specific cultural contexts are submitted to different laboratories and at different times. In this situation, the issue of comparability between results and amongst laboratories becomes paramount. Users of the results from 14C dating are also concerned with the comparability and quality of laboratory results and the quality assurance programs that laboratories undertake are thus important in ensuring user confidence. The harmonization of measurements and the traceability of results to internationally recognized standards are also major goals of the program of work described in this special issue.

Each material needs to be characterized by estimating its activity, which creates a reference value for each material. This value then can be considered as the “known” activity of the material and future analyses can be compared to this to quantify the accuracy of the measurement. In this way, the materials remain useful for laboratory quality assurance.

As part of the FIRI program, it was recognized that providing samples in sufficient quantity for laboratory procedures is close to ideal and does not represent “typical” conditions. Therefore, laboratories were asked to consider 2 optional studies: investigating the effects of sample size on results and achieving high precision. The sample size study was focused on Sample E, humic acid, which had been chosen because of the rigorous pretreatment it had undergone in the solution stage, and which would ensure sample homogeneity. The precision study was focused on Sample D, the Belfast dendro-dated wood sample, given its importance in the master calibration.

In this section, we present the exploratory analysis of the results submitted by the extended deadline of December 2000. We first deal with Samples C.J, before considering the near-background samples A and B (Kauri wood). The aims of the exploratory analysis are to discover the range of results reported for each sample and the initial evaluation of the effects of any factors that might be a source of variation in the results. For each sample, in turn, we consider the main summary statistics.the number of results reported (N), their mean or average, median, the standard deviation (StDev), the standard error of the mean (Sem), the quartiles (25th [Q1] and 75th [Q3] percentiles), and the minimum (Min) and maximum (Max)—before graphically studying the overall distribution of results in the form of a boxplot, with a view to identifying any extreme or outlying observations. The summary statistics and distribution of results for each laboratory type are also shown. Further details on the statistical methods used are contained in Appendix 3.

The design of FIRI is such that for each laboratory, we have some basic, though limited, information on the laboratory procedures, including the method of pretreatment applied to the samples, the modern standard, and the background material used. These can be considered as factors in the experiment and through statistical analysis, we can investigate whether they offer a statistically significant explanation of the observed variation. The different levels of the factors are described in Table 4.1. In addition, the laboratory type is also considered as a further factor (with 3 levels of LSC, GPC, and AMS).

OBJECTIVES To describe the development of a facial expression tool differentiating pain-free cats from those in acute pain. METHODS Observers shown facial images from painful and pain-free cats were asked to identify if they were in pain or not. From facial images, anatomical landmarks were identified and distances between these were mapped. Selected distances underwent statistical analysis to identify features discriminating pain-free and painful cats. Additionally, thumbnail photographs were reviewed by two experts to identify discriminating facial features between the groups. RESULTS Observers (n = 68) had difficulty in identifying pain-free from painful cats, with only 13% of observers being able to discriminate more than 80% of painful cats. Analysis of 78 facial landmarks and 80 distances identified six significant factors differentiating pain-free and painful faces including ear position and areas around the mouth/muzzle. Standardised mouth and ear distances when combined showed excellent discrimination properties, correctly differentiating pain-free and painful cats in 98% of cases. Expert review supported these findings and a cartoon-type picture scale was developed from thumbnail images. CLINICAL SIGNIFICANCE Initial investigation into facial features of painful and pain-free cats suggests potentially good discrimination properties of facial images. Further testing is required for development of a clinical tool

In all facets of animal welfare, as in human health and quality of life, the unambiguous and valid measurement of the key attributes is of critical importance. Welfare is a complex construct and in this paper we present a methodological framework for the development of a composite animal welfare scale based on psychometric and metrological principles for scale creation developed in human medicine and Psychology. We indicate how these principles can be applied and how the resulting scale would then be validated and tested.

The purpose of this study was to compare resistance and cross-resistance development in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients to commonly used antipseudomonal antibiotics. Isolates were repeatedly exposed to subinhibitory concentrations of either azlocillin, tobramycin, ceftazidime or ciprofloxacin. On 10 consecutive occasions, samples were removed from the half-MIC well of a microtitre plate and regrown in drug-free medium to provide the next inoculum for MIC determination. The increase in MIC at the end of the treatment period was significant (p

A study was designed to investigate the association between heart rate, respiratory rate and pupil dilation and a subjective pain score allocated using a numerical rating scale (NRS). Four groups of dogs (n = 17 to 20 per group) were included: orthopaedic surgery cases, soft tissue surgery cases, dogs with medical conditions and healthy dogs. Each dog was examined by five veterinary surgeons within a four-hour period. When examining each dog, the observers recorded heart rate, respiratory rate, pupil dilation (present or absent) and a pain score using a NRS (range 0 to 10). For surgical cases, all study assessments were carried out between 21 and 27 hours following the end of surgery. The correlation coefficients between physiological parameters and NRS score were small but, depending on the analysis, were significant for heart rate and NRS score (P < 0·05). However, the size of the coefficient, 0·168, indicated that the relationship was not biologically significant. There was no association between respiratory rate and NRS score. Analysis of the relationship between NRS score and pupil dilation indicated that there was an association between this factor and pain, depending on the analysis. This was significant for the surgical groups (P < 0·05) but not for the other groups. These findings indicate that heart rate and respiratory rate are not useful indicators of pain in hospitalised dogs. It is also unlikely that pupil dilation will be a useful tool in the assessment of pain.

There has recently been growing concern over the dumping of high- and medium-level solid radioactive wastes in the Kara Sea by the former Soviet Union. The largest amounts of radioactive wastes were dumped primarily as nuclear reactors containing spent nuclear fuel. The present radionuclide inventory in dumped nuclear reactors is estimated at 4·7 PBq. Compartmental and hydrodynamic models have been developed and applied to describe the possible dispersal of radioactive contaminants and to predict the long-term radiological impact on global, regional and local scales. The collective committed effective dose to the world population based on the marine food ingestion pathway has been calculated as 2·2 man Sv. Modelling results suggest that only radiological effects on a local scale may be of importance. The global radiological impact of the disposals in the Kara Sea will be smaller than from other anthropogenic sources of radioactivity.

All measurement is subject to uncertainty. Every time an analytical carbon-14 ( 14 C) measurement is made, a different result is obtained. An estimate of analytical uncertainty is made reflecting the range of values within which the true value is expected to lie. The uncertainty of a measurement describes the spread of values, which might be observed if the measurement were repeated under identical conditions, being characterized by a standard deviation. For a single estimated 14 C age, the commonly quoted error is based on counting statistics, but it may also include components introduced by other laboratory corrections. Such estimates may then be combined with those from the replicate series of measurements to provide the calculation of the overall uncertainty on a 14 C measurement. An additional source of uncertainty is derived in calibration. The relationship between the estimated 14 C age and the true age is a complex, often nonlinear, form. The error in years before present on the estimated 14 C age must also undergo a transformation to give the corresponding error on the calendar-year scale. However, complexities arise due to the complex pattern of 14 C variations, often resulting in greater uncertainty on the calibrated-age scale.

Micro‐ and nanoparticles prepared from the biodegradable and biocompatible polymers poly(lactide‐co‐glycolide) (PLGA) and polymethylmethacrylate (PMMA) have been successfully used as immunopotentiating antigen delivery systems. In our study, this approach was used to improve polyclonal antibody production to clenbuterol (CBL), a model hapten. PLGA and PMMA nanoparticles were loaded with either CBL alone or with a clenbuterol‐transferrin conjugate (CBL—Tfn) and administered subcutaneously to mice. PLGA nanoparticles were administered with or without the saponin adjuvant Quil A. The anti‐CBL titres present in experimental sera were determined by an enzyme immunoassay (ELISA). CBL‐Tfn‐loaded PLGA nanoparticles co‐administered with Quil A had obvious advantages immunologically over the currently used method of raising antibodies to CBL (the positive control). The combined adjuvanticity of Quil A and PLGA nanoparticles resulted in a positive response in all four of the mice tested and in higher antibody titres...

Community pharmacists' awareness of the COMA report on “Weaning and the weaning diet” and their knowledge of its recommendations was assessed in a questionnaire distributed to all (n=81) community pharmacists in the Western Health and Social Services Board in Northern Ireland. Sources of information and adequacy of training on childhood nutritional issues were determined. A knowledge score was computed for each pharmacist depending on their responses to questions based on key issues in the COMA report. Completed questionnaires were returned by 48 pharmacists (59 per cent). The COMA report had been read by 14.5 per cent of respondents while 12.5 per cent knew of its recommendations. Others had heard of it but not read it (52 per cent) or had never heard of it (21 per cent). The mean knowledge score was 66 per cent (±17.5). Scores ranged from 18 per cent to 90 per cent, indicating wide variability in pharmacists' knowledge of key recommendations for weaning. Only 29 per cent of pharmacists felt that they were adequately trained to give advice on weaning; 50 per cent felt that they did not have sufficient knowledge and 21 per cent were unsure. Pharmacists indicated that, on average, parents approached them weekly about a weaning topic, which emphasises the need for them to be well informed about current weaning recommendations.

Objectives To describe the development, preliminary validation and reliability testing of a shortened web-based form of GUVQuest, a structured questionnaire to measure health-related quality of life in dogs. Methods The original 109 items were reduced using expert judgement and factor analysis. Validity was established by factor analysis and in a subsequent field trial using a “known groups” approach and classical test theory. Test–retest reliability was assessed using intraclass correlation coefficients. Results The instrument comprises 46 items each of which is rated by dog owners using a 7-point Likert scale. Factor analysis revealed a sensible structure containing four health-related quality of life domains (vitality, pain, distress and anxiety) accounting for 64·1% of the variability in the data. The field test involving 125 dogs demonstrated very good discriminative properties and intraclass correlation coefficient values of greater than 0·6. Clinical Significance This is the first report of a valid and reliable companion animal health-related quality of life instrument, the contemporary approach to animal welfare measurement, which is presented in a web-based format, with automated production of a health-related quality of life profile. It offers major advantages to dog owners, practitioners and researchers.

Spatial variability is an important feature in many environmental studies, which influences comparison estimates of environmental radioactivity from soil samples and in-situ or airborne γ-ray spectrometry. Comparisons between ground based and airborne gamma ray spectrometry are needed both for interpretation and for calibration purposes. However, under normal environmental conditions such comparisons may be affected by the considerable differences in the spatial response of these measurement techniques. A sampling methodology is presented which enables soil sample derived estimates of environmental radioactivity to be effectively compared with in-situ and aerial survey results. Examples of calibration sites and derived sensitivity estimates for 137 Cs are presented for a range of environmental contexts.

The use of in-situ gamma ray spectrometry provides a means of rapidly estimating environmental radioactivity inventories. However, one of the principal limitations of this technique has been the influence of variations in vertical activity distribution on the observed photon fluence. This paper demonstrates that the quantification of the forward scattered ratio of the spectrum ( Q ) can be used to: (i) estimate the mean mass depth (β) of the vertical activity distribution within sediment profiles, and (ii) provide a calibration correction coefficient for in-situ gamma spectrometry in environments which exhibit variable and non-exponential activity distributions, such as salt marshes around the Irish Sea. This paper presents a successful application of a spectrally derived calibration correction coefficient to in-situ spectra from a salt marsh at Caerlaverock, Dumfries, SW Scotland, improving the correlation between soil core and in-situ derived activity estimates from r 2 = 0.097 (uncorrected) to r 2 = 0.801 (corrected). The scope for extending this approach to a wider range of environments, to airborne gamma spectrometry and to measurements of sedimentation rates is considered.

All measurement is subject to uncertainty. Every time an analytical carbon-14 ( 14 C) measurement is made, a different result is obtained. An estimate of analytical uncertainty is made reflecting the range of values within which the true value is expected to lie. The uncertainty of a measurement describes the spread of values, which might be observed if the measurement were repeated under identical conditions, being characterized by a standard deviation. For a single estimated 14 C age, the commonly quoted error is based on counting statistics, but it may also include components introduced by other laboratory corrections. Such estimates may then be combined with those from the replicate series of measurements to provide the calculation of the overall uncertainty on a 14 C measurement. An additional source of uncertainty is derived in calibration. The relationship between the estimated 14 C age and the true age is a complex, often nonlinear, form. The error in years before present on the estimated 14 C age must also undergo a transformation to give the corresponding error on the calendar-year scale. However, complexities arise due to the complex pattern of 14 C variations, often resulting in greater uncertainty on the calibrated-age scale.

The non-parenteral delivery of vaccines is reviewed with emphasis on particulate systems. The oral route predominates although there is now increasing work on the nasal routes of delivery. Intravaginal and intrarectal delivery makes use of the common mucosal immune system. Published work suggests that single dose mucosal vaccination using a biodegradable controlled-release delivery system is now a viable proposition. Drug regulatory aspects are considered and some of the control procedures necessary highlighted.

The appropriateness of empiric therapy, how closely prescribers adhered to hospital guidelines for use of antimicrobial drugs and how relevant these guidelines proved in providing cover for the infecting pathogen were assessed from a retrospective survey of culture and sensitivity reports issued during a one-month period in a district general hospital. Blood, stool, pus, sputum and mid-stream urine specimens were reviewed. Urine specimens from a fundholding general practice unit were also included. Catheter specimens of urine and specimens from other body sites were excluded. Of 290 specimens sent for culture, 99 (34 per cent) were positive. One hundred patients, of whom 54 (19 per cent of the total) were subsequently demonstrated to have a positive culture, had been treated empirically. In 38 per cent of cases the pre-report empiric treatment was considered appropriate for the isolated pathogen, while 46 per cent of patients had negative cultures and 16 per cent had positive cultures but had been given unsuitable antibiotics. In hospitalised patients, 73 per cent of antibiotic treatments were prescribed according to hospital guidelines, although this was the case for only 45 per cent of community-based patients. Hospital guidelines were a relevant and useful aid to rational prescribing in that 75 per cent of organisms isolated were sensitive to guideline antibiotics. The guidelines were least appropriate for urine specimens from hospital. This reflects the range of organisms encountered and the emergence of resistant strains, reinforcing the need for regular updating and amending of prescribing recommendations.

Background: Terbinafine has a broad spectrum of action in vitro and primary fungicidal action against many pahtogenic fungi. Its mode of action against dermatophyte fungi in nail keratin is little understood. Objective: Our purpose was to determine the bioavailability of terbinafine in a nail fragment model. Methods: The effect of terbinafine on adherence and germination of arthroconidia of Trichophyton mentagrophytes on nail fragments was assessed by gross examination and light and electron microscopy. Results: Preexposure of nail fragments to terbinafine concentrations (0.001 to 10 mg/L) inhibited fungal growth and acted as a barrier to dermatophyte invasion. Damaged arthroconidia and distorted hyphae on the surface of nail fragments were observed. Conclusion: This in vitro model provides an alternative system for studying the activity of antifungal agents in nail and demonstrates the morphologic changes in dermatophyte fungi after exposure to terbinafine.

There has been world-wide concern over the possible health and environmental impacts of the dumping of radioactive wastes in shallow waters of the Kara and Barents Seas. During 1992, IAEA-MEL participated in a joint Russian-Norwegian expedition to the region and collected a suite of sediment cores for characterization of downcore radioactivity distribution patterns and inventories with the aim of assessing past and present inputs of radionuclides. The 137Cs, 238Pu, 239,240Pu, and 241Am contents of the 0–1 cm sections range from 17 to 32, 0·01 to 0·06, 0·4 to 1·3 and 0·2 to 0·5 Bq kg−1 (dry wt), respectively. The 238Pu/239,240Pu and 241Am/239,240Pu activity ratios are consistent with those reported for global fallout. Detailed information on downcore radionuclide distribution patterns and inventories, as well as an account of sedimentation parameters, are presented. A preliminary assessment of the long-term radiological impact of radioactive waste disosal in the Arctic Seas, on global and regional scales, has been made. The modelling results suggest that the global radiological impact of the disposals will be comparable to or less than those resulting from other anthropogenic and natural sources of radioactivity. However, radiological effects on the regional scale may be of importance. IAEA is carrying out a 4 year International Arctic Seas Assessment Project (IASAP) that will comprehensively cover all aspects of radioactive dumping in the Arctic Seas and it will be reported to the London Convention in 1996. The IAEA-MEL study described here represents a preliminary contribution to IASAP.

The association (adherence) between human corneocytes and arthroconidia of Trichophyton mentagrophytes strains 121 and 126, and T. interdigitale strain 4 was studied in vitro. Adherence of arthroconidia to corneocytes from either the palm and sole occurred and increased with time up to 6 h, by which time germination of arthroconidia had started. Significant differences were seen between the T. mentagrophytes strains and T. interdigitale in their adherence to corneocytes from the palm. When adherence values for plantar corneocytes were compared, significant differences were found between T. mentagrophytes and T. interdigitale. Not all corneocytes from either site had adherent arthroconidia, although there was a time-dependent increase in the numbers of corneocytes with adherent fungal cells. By scanning and transmission electron microscopy it was seen that there was a loose association between arthroconidia and corneocytes with no apparent damage to the corneocyte membrane. Adherence of germlings of T. interdigitale to corneocytes from the palm appeared to be mediated by germling outer cell wall fibrils. Hyphal branches and secondary germlings were observed to enhance the attachment of the parent hypha to adjacent corneocytes.

The morphological modifications of arthroconidia and germ tubes of Trichophyton interdigitale exposed to terbinafine (6·25–100 mgl-1) incorporated into stratum corneum were studied by scanning and transmission electron microscopy after 16 h and 20 h. Changes in arthroconidial morphology were apparent at 16 h. Pores and erosions were present in the cell wall with layers peeling off. The cell membrane was destroyed. Dilated vacuoles and small electron dense areas were evident in the arthroconidial cytosol. Although germination was not arrested, inhibition of hyphal extension was seen. Germ tubes were susceptible to terbinafine with pores appearing along their length following exposure to the drug. Germ tubes were seen to have collapsed at higher drug concentrations. The study suggests that the outer and inner layers of the arthroconidial cell wall are the initial targets of terbinafine action followed by alterations to the cytosol and intracellular organelles.