An ethogram for Equitation Science First Principles of Horse Training

This ethogram is based on Equitation Science’s ‘First Principles of Horse Training’. This is related to: North, S. 2016. Software Program: IPTEK (ISES Principles Training Evaluation Kit). DOI: 10.5281/zenodo.54821. Available from: http://dx.doi.org/10.5281/zenodo.54821 North, S., Hemingway, A., McLean, A. N., Laurie, H. & Ellis-Hill, C. 2016. How does Parelli measure up? (poster). In Proceedings of the 12th International Society for Equitation Science Conference (ISES2016) (ifce - institut français du cheval et de l’équitation, Saumur, France. June 23-25 2016). International Society for Equitation Science. http://dx.doi.org/10.13140/RG.2.1.3055.0644 North, S., Hemingway, A., McLean, A. N., Laurie, H. & Ellis-Hill, C. 2016. Evaluating a natural horsemanship program in relation to the ISES first principles of horse training. In Proceedings of the 12th International Society for Equitation Science Conference (ISES2016) (ifce - institut français du cheval et de l’équitation, Saumur, France. June 23-25 2016). International Society for Equitation Science. http://dx.doi.org/10.5281/zenodo.54733 North, S., Hemingway, A., McLean, A. N., Laurie, H. & Ellis-Hill, C. 2016. Evaluating a natural horsemanship program in relation to the ISES first principles of horse training. Journal of Veterinary Behavior: Clinical Applications and Research, 15, September–October, p.87. http://dx.doi.org/10.1016/j.jveb.2016.08.040. ISSN: 1558-7878 The ethogram for Equitation Science First Principles of Horse Training is intended to evaluate a method of horse training, ideally, from video recordings. It should be noted that each behavior in the ethogram is followed by its inverse: “INCORRECTLY describing or demonstrating…”. This allows logged observations to include examples that contradict the ISES ‘First Principles’ (should any be present). This is important because, whereas the absence of a specific principle might simply be a matter of differing emphasis, contradiction might indicate a more serious discongruity. The proposed ethogram is of human behaviour during horse training. It does not consider the horse-human dyad, during training interactions. Of course the horse’s response to human training is very informative. This ethogram maps directly to equitation science’s ‘first principles’, which only describe the human aspects of an idealised horse / horsemanship training program. Therefore, horse behaviours do not feature in the ethogram

Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations.

$\textit{Objectives}$: To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. $\textit{Methods}$: Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight $b$ values (0, 30, 60, 90, 120, 300, 600, 900 s/mm$^2$). Apparent diffusion coefficient (ADC), tissue diffusion coefficient ($D_t$), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha ($\alpha$) parameters were derived. Then $t$ tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. $\textit{Results}$: All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups ($p$ < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) ($p$ = 0.03, $p$ = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. $\textit{Conclusion}$: DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes.The study has received funding from the Addenbrookes Charitable Trust and the NIHR comprehensive Biomedical Research Centre (BRC) and the Experimental Cancer Medicine Centre (ECMC) awards to Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge

The Evolution of the Stellar Hosts of Radio Galaxies

We present new near-infrared images of z>0.8 radio galaxies from the flux-limited 7C-III sample of radio sources for which we have recently obtained almost complete spectroscopic redshifts. The 7C objects have radio luminosities about 20 times fainter than 3C radio galaxies at a given redshift. The absolute magnitudes of the underlying host galaxies and their scale sizes are only weakly dependent on radio luminosity. Radio galaxy hosts at z~2 are significantly brighter than the hosts of radio-quiet quasars at similar redshifts and the model AGN hosts of Kauffmann & Haehnelt (2000). There is no evidence for strong evolution in scale size, which shows a large scatter at all redshifts. The hosts brighten significantly with redshift, consistent with the passive evolution of a stellar population that formed at z>~3. This scenario is consistent with studies of host galaxy morphology and submillimeter continuum emission, both of which show strong evolution at z>~2.5. The lack of a strong ``redshift cutoff'' in the radio luminosity function to z>4 suggests that the formation epoch of the radio galaxy host population lasts >~1Gyr from z>~5 to z~3. We suggest these facts are best explained by models in which the most massive galaxies and their associated AGN form early due to high baryon densities in the centres of their dark matter haloes.Comment: To appear in A

Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations.

OBJECTIVES: To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. METHODS: Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D t), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. RESULTS: All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. CONCLUSION: DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. KEY POINTS: • Baseline diffusion coefficients demonstrated significant differences between complete pathological responders and non-responders. • Increase in ADC and DDC at mid-treatment can discriminate responders and non-responders. • The ƒ fraction at mid-treatment decreased in responders whereas increased in non-responders. • The mono- and stretched-exponential models showed excellent inter- and intrarater repeatability. • Treatment effects can potentially be assessed by non-mono-exponential diffusion models.The study has received funding from the Addenbrookes Charitable Trust and the NIHR comprehensive Biomedical Research Centre (BRC) and the Experimental Cancer Medicine Centre (ECMC) awards to Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge

The 2020 Five Domains Model: Including Human-Animal Interactions in Assessments of Animal Welfare

Throughout its 25-year history, the Five Domains Model for animal welfare assessment has been regularly updated to include at each stage the latest authenticated developments in animal welfare science thinking. The domains of the most up-to-date Model described here are: 1 Nutrition, 2 Physical Environment, 3 Health, 4 Behavioural Interactions and 5 Mental State. The first four domains focus attention on factors that give rise to specific negative or positive subjective experiences (affects), which contribute to the animal’s mental state, as evaluated in Domain 5. More specifically, the first three domains focus mainly on factors that disturb or disrupt particular features of the body’s internal stability. Each disturbed or disrupted feature generates sensory inputs which are processed by the brain to form specific negative affects. These affects are associated with behaviours that act to restore the body’s internal stability. Each such behaviour is essential for the survival of the animal

Exploring the biochemistry at the extracellular redox frontier of bacterial mineral Fe(III) respiration

Many species of the bacterial Shewanella genus are notable for their ability to respire in anoxic environments utilizing insoluble minerals of Fe(III) and Mn(IV) as extracellular electron acceptors. In Shewanella oneidensis, the process is dependent on the decahaem electron-transport proteins that lie at the extracellular face of the outer membrane where they can contact the insoluble mineral substrates. These extracellular proteins are charged with electrons provided by an inter-membrane electron-transfer pathway that links the extracellular face of the outer membrane with the inner cytoplasmic membrane and thereby intracellular electron sources. In the present paper, we consider the common structural features of two of these outer-membrane decahaem cytochromes, MtrC and MtrF, and bring this together with biochemical, spectroscopic and voltammetric data to identify common and distinct properties of these prototypical members of different clades of the outer-membrane decahaem cytochrome superfamily

A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-12, pub-electronic 2021-10-21Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/M011208/1CYP102A1 (BM3) is a catalytically self-sufficient flavocytochrome fusion protein isolated from Bacillus megaterium, which displays similar metabolic capabilities to many drug-metabolizing human P450 isoforms. BM3′s high catalytic efficiency, ease of production and malleable active site makes the enzyme a desirable tool in the production of small molecule metabolites, especially for compounds that exhibit drug-like chemical properties. The engineering of select key residues within the BM3 active site vastly expands the catalytic repertoire, generating variants which can perform a range of modifications. This provides an attractive alternative route to the production of valuable compounds that are often laborious to synthesize via traditional organic means. Extensive studies have been conducted with the aim of engineering BM3 to expand metabolite production towards a comprehensive range of drug-like compounds, with many key examples found both in the literature and in the wider industrial bioproduction setting of desirable oxy-metabolite production by both wild-type BM3 and related variants. This review covers the past and current research on the engineering of BM3 to produce drug metabolites and highlights its crucial role in the future of biosynthetic pharmaceutical production

The dynamics of measles in sub-Saharan Africa.

Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population.

OBJECTIVE: To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population. METHODS: Thirty-patients were imaged at 3 T including DKI (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics. RESULTS: Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825). CONCLUSION: ADC, Dapp, Kapp and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease. KEY POINTS: • MTR was significantly higher in PZ and TZ tumours versus normal tissue • K app was significantly lower and D app higher for PZ and TZ tumours • There was no incremental value for DKI/MTI over mono-exponential ADC parameters • No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease • Divergent MTR/DKI values in TZ tumours suggests they offer different functional information

Accelerating clinical development of a live attenuated vaccine against Salmonella Paratyphi A (VASP): study protocol for an observer-participant-blind randomised control trial of a novel oral vaccine using a human challenge model of Salmonella Paratyphi A infection in healthy adult volunteers

Introduction: This is the first efficacy study of an oral live attenuated vaccine against Salmonella Paratyphi A using a human challenge model of paratyphoid infection. S. Paratyphi A is responsible for 3.3 million cases of enteric fever every year, with over 19 000 deaths. Although improvements to sanitation and access to clean water are vital to reduce the burden of this condition, vaccination offers a cost-effective, medium-term solution. Efficacy trials of potential S. Paratyphi vaccine candidates in the field are unlikely to be feasible given the large number of participants required. Human challenge models therefore offer a unique, cost-effective solution to test efficacy of such vaccines. Methods and analysis: This is an observer-blind, randomised, placebo-controlled trial phase I/II of the oral live-attenuated vaccine against S. Paratyphi A, CVD 1902. Volunteers will be randomised 1:1 to receive two doses of CVD 1902 or placebo, 14 days apart. One month following second vaccination all volunteers will ingest S. Paratyphi A bacteria with a bicarbonate buffer solution. They will be reviewed daily in the following 14 days and diagnosed with paratyphoid infection if the predefined microbiological or clinical diagnostic criteria are met. All participants will be treated with antibiotics on diagnosis, or at day 14 postchallenge if not diagnosed. The vaccine efficacy will be determined by comparing the relative attack rate, that is, the proportion of those diagnosed with paratyphoid infection, in the vaccine and placebo groups. Ethics and dissemination: Ethical approval for this study has been obtained from the Berkshire Medical Research Ethics Committee (REC ref 21/SC/0330). The results will be disseminated via publication in a peer-reviewed journal and presentation at international conferences. Trial registration number: ISRCTN15485902