Detection of Toxicity in Ruminants Consuming Leucaena (\u3cem\u3eLeucaena leucocephala\u3c/em\u3e) Using a Urine Colorimetric Test

Leucaena (Leucaena leucocephala), a productive leguminous shrub for feeding ruminant livestock, contains the toxic amino acid, mimosine which post- ingestion is converted to 3,4-DHP and 2,3-DHP, isomers of dihydroxy-pyridone. While DHP generally does not exhibit acute toxic symptoms, it has been suggested that it is an appetite suppressant that reduces animal live weight gain (Jones 1994). With no observable symptoms, subclinical toxicity is difficult to detect (Phaikaew et al. 2012). In 1982 the DHP-degrading rumen bacterium named Synergistes jonesii was introduced into Australia as a potential solution to DHP toxicity as it spreads easily throughout cattle herds grazing leucaena (Jones 1994). However, toxicity events reported since the 2003 drought suggest that the toxicity status of herds, previously understood as being protected, may have changed. This may be the result of loss of effective S. jonesii bacteria from the rumen. Widespread subclinical leucaena toxicity has since been confirmed representing a significant economic threat to the beef industry (Dalzell et al. 2012). At present the testing for toxicity requires a sophisticated chemical analysis of urine samples using high performance liquid chromatography (HPLC). Producers, however, require a robust and reliable means to routinely test for toxicity in their herds. A colorimetric urine test protocol is available based on the colour reaction of mimosine and DHP with FeCl3 solution (Jones 1997). When this simpler colorimetric test has been used under a wide range of conditions false negatives have been reported. The aim of this study was to improve the reliability of the FeCL3 urine colour test

Rates of Urinary Toxin Excretion in Unprotected Steers Fed \u3cem\u3eLeucaena leucocephala\u3c/em\u3e

Leucaena (Leucaena leucocephala) is a productive, nutritious, leguminous forage tree with high capacity for ruminant live weight gain. The plant does however contain the non-protein amino acid mimosine which is degraded within the rumen to 3-hydroxy-4(1H)-pyridone (3,4-DHP) with potential to cause adverse effects on animal health and production. Stock can be protected via rumen inoculation with the bacterium Synergistes jonesii, which is capable of degrading the toxin. However surveys have demonstrated sub-clinical toxicity is persisting in Queensland herds (Dalzell et al. 2012). Currently, testing for toxicity involves analysis of urine samples using high performance liquid chromatography (HPLC). A colorimetric urine test protocol has also been developed with the aim of providing a robust and reliable means for routinely testing herds (Graham et al. 2013). A significant problem affecting interpretation of the results from either method is the high variation in the concentrations of toxins excreted among animals on similar diets and by individual animals over time (Dalzell et al. 2012). Factors such as feed intake, water consumption, urine volume, as well as timing of sampling may be the cause of this variation. This research investigated the effect of sample timing by measuring the time taken for mimosine and its breakdown products, to present in the urine following the introduction of leucaena to the ration of cattle naïve to the plant

On the Feasibility of Imaging Carbonatite-Hosted Rare Earth Element Deposits Using Remote Sensing

Rare earth elements (REEs) generate characteristic absorption features in visible to shortwave infrared (VNIR-SWIR) reflectance spectra. Neodymium (Nd) has among the most prominent absorption features of the REEs and thus represents a key pathfinder element for the REEs as a whole. Given that the world’s largest REE deposits are associated with carbonatites, we present spectral, petrographic, and geochemical data from a predominantly carbonatitic suite of rocks that we use to assess the feasibility of imaging REE deposits using remote sensing. Samples were selected to cover a wide range of extents and styles of REE mineralization, and encompass calcio-, ferro- and magnesio-carbonatites. REE ores from the Bayan Obo (China) and Mountain Pass (United States) mines, as well as REE-rich alkaline rocks from the Motzfeldt and Ilímaussaq intrusions in Greenland, were also included in the sample suite. The depth and area of Nd absorption features in spectra collected under laboratory conditions correlate positively with the Nd content of whole-rock samples. The wavelength of Nd absorption features is predominantly independent of sample lithology and mineralogy. Correlations are most reliable for the two absorption features centered at ~744 and ~802 nm that can be observed in samples containing as little as ~1,000 ppm Nd. By convolving laboratory spectra to the spectral response functions of a variety of remote sensing instruments we demonstrate that hyperspectral instruments with capabilities equivalent to the operational Airborne Visible-Infrared Imaging Spectrometer (AVIRIS) and planned Environmental Mapping and Analysis Program (EnMAP) systems have the spectral resolutions necessary to detect Nd absorption features, especially in high-grade samples with economically relevant REE accumulations (Nd > 30,000 ppm). Adding synthetic noise to convolved spectra indicates that correlations between Nd absorption area and whole-rock Nd content only remain robust when spectra have signal-to-noise ratios in excess of ~250:1. Although atmospheric interferences are modest across the wavelength intervals relevant for Nd detection, most REE-rich outcrops are too small to be detectable using satellite-based platforms with >30-m spatial resolutions. However, our results indicate that Nd absorption features should be identifiable in high-quality, airborne, hyperspectral datasets collected at meter-scale spatial resolutions. Future deployment of hyperspectral instruments on unmanned aerial vehicles could enable REE grade to be mapped at the centimeter scale across whole deposits

Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study

<p>Background: Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM.</p> <p>Methods and Findings: The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005–2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4–3.8, p<0.001) than men (2.3: 2.0–2.7, p<0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2–3.0, p<0.001) in men and 2.7 (2.2–3.4, p<0.001) in women. Between 2005–2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were <40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60–69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA1c of <7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used.</p> <p>Conclusions: Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed.</p&gt

Acceptance and Commitment Therapy for muscle disease (ACTMus) : protocol for a two-arm randomised controlled trial of a brief guided self-help ACT programme for improving quality of life in people with muscle diseases

Introduction In adults, muscle disease (MD) is often a chronic long-term condition with no definitive cure. It causes wasting and weakness of the muscles resulting in a progressive decline in mobility, alongside other symptoms, and is typically associated with reduced quality of life (QoL). Previous research suggests that a psychological intervention, and in particular Acceptance and Commitment Therapy (ACT), may help improve QoL in MD. ACT is a newer type of cognitive behavioural treatment that aims to improve QoL by virtue of improvement in a process called psychological flexibility. The primary aim of this randomised controlled trial (RCT) is to evaluate the efficacy of a guided self-help ACT programme for improving QoL in people with MD. Main secondary outcomes are mood, symptom impact, work and social adjustment and function at 9-week follow-up. Methods and analysis Acceptance and Commitment Therapy for Muscle Disease is an assessor-blind, multicentre, two-armed, parallel-group RCT to assess the efficacy of ACT plus standard medical care (SMC) compared with SMC alone. Individuals with a diagnosis of one of four specific MDs, with a duration of at least 6 months and with mild to moderate anxiety or depression (Hospital Anxiety and Depression Scale score ≥8) will be recruited from UK-based MD clinics and MD patient support organisations. Participants will be randomised to either ACT plus SMC or SMC alone by an independent randomisation service. Participants will be followed up at 3, 6 and 9 weeks. Analysis will be intention to treat, conducted by the trial statistician who will be blinded to treatment allocation. Ethics and dissemination The study has received full ethical approval. Study results will be disseminated via peer-reviewed publications, conference presentations and journal articles. Data obtained from the trial will enable clinicians and health service providers to make informed decisions regarding the efficacy of ACT for improving QoL for patients with MD. Trial registration number NCT02810028. Protocol version V.11 (4 April 2017)

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

Cohort profile : the Scottish Diabetes Research Network national diabetes cohort - a population-based cohort of people with diabetes in Scotland

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Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context

Background: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. Aims: The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. Method: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. Results: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. Conclusion: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk

Attitudes Toward Disability: The Relationship Between Attitudes Toward Disability and Frequency of Interaction with People with Disabilities (PWD)

The social and medical models of disability are sets of underlying assumptions explaining people's beliefs about the causes and implications of disability. The medical model is the predominant model in the United States that is associated with the belief that disability is an undesirable status that needs to be cured (Darling & Heckert, 2010). This model focuses on the diagnosis, treatment and curative efforts related to disability. The social model is preferred by disability activists and researchers which focuses on society’s involvement in disability, such as stigmatization, discrimination and the interpersonal barriers that are features of one’s disability. The social model suggests that society disables individuals and is the cause of impairment (Olkin, 2003). Allport’s contact hypothesis states that increased contact with people with disabilities (PWD) will reduce prejudice through relationship building and social connection (Allport, 1954). Pettigrew’s Intergroup Contact Theory, similar to Allport’s contact hypothesis, argues that essential conditions must be met in order to reduce feelings of prejudice. These conditions are: learning about the outgroup, changing behavior, generating affective ties, and ingroup reappraisal (Pettigrew, 1998). Based on these theories, increased interaction with PWD should result in more favorable attitudes about PWD. We further propose that contact may serve to alter disability model orientation, which in turn may affect attitudes. This is the first large-scale study that examines how disability models influence the relationship between contact and attitudes toward PWD. It was hypothesized that participants with more frequent interactions with PWD would have more favorable attitudes towards disability. This would be mediated by models of disability. Participants of the study were undergraduate students enrolled in a required university course, with a majority of them being in their first year. The survey consisted of the Attitudes Toward Disabled Persons scale, a single item assessing frequency of contact with PWD, and the Darling (2013) social and medical model scales, and was distributed to a total of 1,506 students. Supporting our hypothesis, the medical and social models partially mediated the relationship between contact and attitudes towards disability. Medical model compared to social model was more strongly associated with contact and attitudes. This suggests that contact with PWD can help decrease medical model beliefs in general, but is less effective at promoting social model beliefs. Implications of this study might suggest that more frequent contact with PWD on college campuses could be possible by hiring more educators who disclose their disability or accommodate to more people with disabilities as students. As for future directions of this study, an expansion beyond college students could provide insight into different demographics and their attitudes toward disability, and could also reveal the potential influence of cohort effects. Future studies may also want to further assess to what degree attitudes and perceptions about PWD change when certain conditions are met, such as those mentioned in Pettigrew’s Intergroup Contact Theory