Effect of plant-derived antimicrobials, eugenol, carvacrol, and ß-resorcylic acid against Salmonella on organic chicken wings and carcasses.

Organic poultry constitutes a sizeable segment of the American organic commodities market. However, processors have limited strategies that are safe, effective, and approved for improving the microbiological safety of products. In this study, the efficacy of 3 plant-derived antimicrobials (PDAs), eugenol (EG), carvacrol (CR), and ß-resorcylic acid (BR) was evaluated against Salmonella on organic chicken wings and carcasses. Wings inoculated with Salmonella (6 log10 CFU/wing) were treated with or without the treatments (BR [0.5%, 1% w/v], EG [0.5%, 1% v/v], CR [0.5%, 1% v/v], chlorine [CL; 200 ppm v/v], or peracetic acid [PA; 200 ppm v/v]) applied for 2 min at 54°C (scalding study) or 30 min at 4°C (chilling study). Homogenates and treatment water were evaluated for surviving Salmonella. Six wings or carcasses per treatment were analyzed in each study. All treatments, except CL and 0.5% BR in the scalding study, yielded significant reductions of Salmonella on wings compared to the positive control (PC-Salmonella inoculated samples not treated with antimicrobials). To follow, carcasses inoculated with Salmonella (higher inoculum [106 CFU/carcass] or lower inoculum [104 CFU/carcass]) and immersed in antimicrobials (CR 1% [v/v] and industry controls [CL {200 ppm}, or PA [200 ppm]) for 30 min at 4°C were stored until analysis. For the higher inoculum study, 1% CR resulted in a 3.9 log10 CFU/g reduction of Salmonella on the carcass on d 0 compared to PC (P < 0.05); however, CL yielded no reduction. On d 3, CR and PA resulted in 0.9 and 1.2 log10 CFU/g reduction of Salmonella, respectively (P < 0.05). For the lower inoculum study, consistent Salmonella reductions were obtained with CR and PA (1.4-2.1 log10 CFU/g) on d 0 and 7. High reductions of Salmonella in processing water were obtained in all studies. CR effectively controls Salmonella on wings and carcasses and in processing water immediately after application. Follow-up studies on the organoleptic characteristics of PDA-treated chicken carcasses are necessary.

DNACPR Decisions: Aligning Law, Guidance, and Practice.

Do not attempt cardiopulmonary resuscitation (DNACPR) decisions are a means to consider in advance the appropriateness of CPR measures if an acute crisis arises. During the COVID-19 pandemic, problems with such decisions, for example the putting in place of DNACPR decisions for all residents of certain care homes, received a lot of attention, prompting a Care Quality Commission (CQC) report with recommendations for improvement. Building on the CQC report, our article addresses a cluster of legal uncertainties surrounding DNACPR decisions, in particular about the grounds for such decisions and the correct procedures for the legally required consultation, including with whom to consult. This article will also analyse commonly used DNACPR forms, as well as the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) form, which aims to incorporate DNACPR decisions as part of more holistic end-of-life care planning. The analysis shows that all forms exhibit shortcomings in reflecting the legal requirements for DNACPR decisions. We recommend a number of changes to the forms aimed at rendering DNACPR practice compliant with the law and more protective of the person's human rights.

COVID-19 and the Mental Capacity Act in care homes: Perspectives from capacity professionals.

This study explores the experiences of professionals who worked with care home residents with impaired mental capacity in England and Wales during the COVID-19 pandemic. It explores (i) how competing risks were balanced and (ii) how the Mental Capacity Act (MCA) functioned in care homes under pandemic conditions, with particular focus on its associated Deprivations of Liberty Safeguards (DoLS) and Independent Mental Capacity Advocacy (IMCA) systems. Between March and May 2021, we held an online survey and five focus groups aimed at professionals who worked in or with care homes during the pandemic. The study explored issues pertaining to residents with impaired mental capacity, alongside several other topics on which we report elsewhere. For this paper, we filtered data to only include responses from 'capacity professionals'. The resulting sample comprised 120 (out of 266) survey participants and 18 (out of 22) focus group participants. We performed manifest content analysis on the filtered data and found that (1) participants reported a 'massive discrepancy' between the ways different care homes balanced the risk of COVID-19 infection with the risks associated with severe restrictions. (2) Some suggested this was due to vague guidance, as well as care home type and size. Participants told us the pandemic (3) obstructed smooth operation of statutory safeguards designed to protect residents' human rights and (4) resulted in confusion about the remit of the MCA during a public health crisis. Our findings raise concerns about the impact of pandemic-related measures upon care home residents with impaired mental capacity. We urge further exploration and analysis of (a) the variability and inconsistency of restrictions applied at care homes, (b) the strain placed on key safeguards associated with the MCA, (c) uncertainty about the remit of the MCA during a public health crisis and (d) the human rights implications hereof.

SIDMA as a criterion for psychiatric compulsion: An analysis of compulsory treatment orders in Scotland.

Scottish mental health legislation includes a unique criterion for the use of compulsion in the delivery of mental health care and treatment. Under the Mental Health (Care and Treatment) (Scotland) Act, 2003, patients must exhibit 'significantly impaired decision-making ability' (SIDMA) in order to be eligible for psychiatric detention or involuntary psychiatric treatment outside the forensic context. The SIDMA requirement represents a distinctive strategy in ongoing international efforts to rethink the conditions under which psychiatric compulsion is permissible. We reconstruct the history of the Scottish SIDMA requirement, analyse its differences from so-called 'fusion law,' and then examine how the SIDMA standard actually functions in practice. We analyse 100 reports that accompany applications for Compulsory Treatment Orders (CTOs). Based on this analysis, we provide a profile of the patient population that is found to exhibit SIDMA, identify the grounds upon which SIDMA is attributed to individual patients, and offer an assessment of the quality of the documentation of SIDMA. We demonstrate that there are systemic areas of poor practice in the reporting of SIDMA, with only 12% of CTOs satisfying the minimum standard of formal completeness endorsed by the Mental Welfare Commission. We consider what lessons might be drawn both for the ongoing review of mental health legislation in Scotland, and for law reform initiatives in other jurisdictions.

Human rights and COVID-19 triage: a comment on the Bath protocol.

In their discussion paper of November 2020, Cook et al present a draft protocol for navigating circumstances in which emergency services are overwhelmed. Their paper suggests that COVID-related triage decisions should be based on clinical assessment, patient and family consultation, and a range of ethical considerations. In this response, we note that the protocol exhibits an ambiguity that is likely to result in irresolvable dilemmas when put into practice. This ambiguity is exemplified in the paper's prime ethical imperative (to 'save more lives and more years of life'), which takes the form of an undefined conjunction whose practical implications are left unspecified. We see this ambiguity in the prime imperative as one manifestation of a broader set of tensions in the protocol. We show that the discipline of human rights provides an essential supplement to the ethical framework on which Cook and colleagues rely, providing a framework for understanding and working through triage dilemmas involving age, discrimination and equality.

Insight Under Scrutiny in the Court of Protection: A Case Law Survey.

The concept of patient insight, of a patient's self-awareness of illness or impairment (and related issues), plays a significant role in clinical discourse and clinical practice. But what role does it play in the legal process, particularly when a patient's decision-making capacity (or "mental capacity") is in question? We report on a survey of 412 published judgments from the Court of Protection of England and Wales, published between 2007 and 2018. We found that the notion of patient insight played a role in 53 cases (13% of the total). We use a variety of techniques to provide a systematic profile of these "insight cases." We provide a demographic profile of the patients whose insight is discussed (focusing on gender, age and diagnosis) and a professional profile of the expert witnesses who raise the issue of insight. We then deploy the technique of "logical geography" to map the meaning of the term insight and the inferential patterns in which reports of patient insight are embedded. We point out that the published insight cases never explicitly define "insight," and that they include no reference to structured instruments or scales for the assessment of insight. We show that the concept of insight, as used in the Court of Protection, is not synonymous with the concept of agreement with a diagnosis of illness; this is at most one of a range of meanings that the concept carries. We show that, despite the fact that the presence or absence of insight is not itself a legal criterion for mental capacity, insightlessness does play a role, and sometimes a decisive role, in shaping findings as regards the presence or absence of mental capacity. Finally, we assess the extent to which expert testimony in the insight cases conforms to the insight-related recommendation of the recent NICE Guideline on Decision-Making and Mental Capacity.

Surveying the Geneva impasse: Coercive care and human rights.

The United Nations human rights system has in recent years been divided on the question as to whether coercive care interventions, including coercive psychiatric care, can ever be justified under UN human rights standards. Some within the UN human rights community hold that coercive care can comply with human rights standards, provided that the coercive intervention is a necessary and proportionate means to achieve certain approved aims, and that appropriate legal safeguards are in place. Others have held that coercive care is never justified. Disagreement over this issue has produced an impasse in the UN human rights system. We survey the impasse with particular attention to the legal arguments that inform the divergent positions. In doing so we introduce a distinction among a variety of different 'abolitionist' positions regarding coercive care, and draw a distinction between 'non-consensual' and 'coercive' treatment. We conclude with three proposals for moving beyond the current impasse.

Manic temporality.

Time-consciousness has long been a focus of research in phenomenology and phenomenological psychology. We advance and extend this tradition of research by focusing on the character of temporal experience under conditions of mania. Symptom scales and diagnostic criteria for mania are peppered with temporally inflected language: increased rate of speech, racing thoughts, flight-of-ideas, hyperactivity. But what is the underlying structure of temporal experience in manic episodes? We tackle this question using a strategically hybrid approach. We recover and reconstruct three hypotheses regarding manic temporality that were advanced and modeled by two pioneers of clinical phenomenology: Eugène Minkowski (1885-1972) and Ludwig Binswanger (1881-1966). We then test, critique, and refine these hypotheses using heterophenomenological methods in an interview-based study of persons with a history of bipolar and a current diagnosis of acute mania. Our conclusions support a central hypothesis due to Minkowski and Binswanger, namely, that disturbance in the formal structure of temporal experience is a core feature of mania. We argue that a suitably refined variant of Binswanger's model of disturbance in manic protention helps to explain a striking pattern of impaired insight and impaired reasoning in manic episodes.

Misevaluating the Future: Affective Disorder and Decision-Making Capacity for Treatment - A Temporal Understanding.

BACKGROUND: Within psychiatric practice and policy there is considerable controversy surrounding the nature and assessment of impairments of decision-making capacity (DMC) for treatment in persons diagnosed with affective disorders. We identify the problems of "cognitive bias" and "outcome bias" in assessment of DMC for treatment in affective disorder and aim to help resolve these problems with an analysis of how time is experienced in depression and mania. SAMPLING AND METHODS: We conducted purposeful sampling and a qualitative phenomenological analysis of interview data on patients with depression and mania, exploring temporal experience and decision-making regarding treatment. RESULTS: In both severe depression and mania there is a distinctive experience of the future. Two consequences can follow: a loss of evaluative differentiation concerning future outcomes and, relatedly, inductive failure. This temporal inability can compromise an individual's ability to appreciate or "use or weigh" treatment information. CONCLUSIONS: The decision-making abilities required for self-determination involve an ability to evaluate alternative future outcomes. Our results show that, within severe depression or mania, anticipation of future outcomes is inflexibly fixed at one end of the value spectrum. We therefore propose a temporal model of decision-making abilities, which could be used to improve assessment of DMC in affective disorder.

Understanding Tail-Biting in Pigs through Social Network Analysis.

The objective of this study was to investigate the association between social structure and incidence of tail-biting in pigs. Pigs (n = 144, initial weight = 7.2 ± 1.57 kg, 4 weeks of age) were grouped based on their litter origin: littermates, non-littermates, and half-group of littermates. Six pens (8 pigs/pen) of each litter origin were studied for 6 weeks. Incidence of tail injury and growth performance were monitored. Behavior of pigs was video recorded for 6 h at 6 and 8 weeks of age. Video recordings were scanned at 10 min intervals to register pigs that were lying together (1) or not (0) in binary matrices. Half weight association index was used for social network construction. Social network analysis was performed using the UCINET software. Littermates had lower network density (0.119 vs. 0.174; p < 0.05), more absent social ties (20 vs. 12; p < 0.05), and fewer weak social ties (6 vs. 14, p < 0.05) than non-littermates, indicating that littermates might be less socially connected. Fifteen percent of littermates were identified as victimized pigs by tail-biting, and no victimized pigs were observed in other treatment groups. These results suggest that littermates might be less socially connected among themselves which may predispose them to development of tail-biting.

Evolution of deep gray matter volume across the human lifespan.

Magnetic resonance imaging of subcortical gray matter structures, which mediate behavior, cognition and the pathophysiology of several diseases, is crucial for establishing typical maturation patterns across the human lifespan. This single site study examines T1-weighted MPRAGE images of 3 healthy cohorts: (i) a cross-sectional cohort of 406 subjects aged 5-83 years; (ii) a longitudinal neurodevelopment cohort of 84 subjects scanned twice approximately 4 years apart, aged 5-27 years at first scan; and (iii) a longitudinal aging cohort of 55 subjects scanned twice approximately 3 years apart, aged 46-83 years at first scan. First scans from longitudinal subjects were included in the cross-sectional analysis. Age-dependent changes in thalamus, caudate, putamen, globus pallidus, nucleus accumbens, hippocampus, and amygdala volumes were tested with Poisson, quadratic, and linear models in the cross-sectional cohort, and quadratic and linear models in the longitudinal cohorts. Most deep gray matter structures best fit to Poisson regressions in the cross-sectional cohort and quadratic curves in the young longitudinal cohort, whereas the volume of all structures except the caudate and globus pallidus decreased linearly in the longitudinal aging cohort. Males had larger volumes than females for all subcortical structures, but sex differences in trajectories of change with age were not significant. Within subject analysis showed that 65%-80% of 13-17 year olds underwent a longitudinal decrease in volume between scans (∼4 years apart) for the putamen, globus pallidus, and hippocampus, suggesting unique developmental processes during adolescence. This lifespan study of healthy participants will form a basis for comparison to neurological and psychiatric disorders. Hum Brain Mapp 38:3771-3790, 2017. © 2017 Wiley Periodicals, Inc.

Clinical assessment of decision-making capacity in acquired brain injury with personality change.

Assessment of decision-making capacity (DMC) can be difficult in acquired brain injury (ABI) particularly with the syndrome of organic personality disorder (OPD) (the "frontal lobe syndrome"). Clinical neuroscience may help but there are challenges translating its constructs to the decision-making abilities considered relevant by law and ethics. An in-depth interview study of DMC in OPD was undertaken. Six patients were purposefully sampled and rich interview data were acquired for scrutiny using interpretative phenomenological analysis. Interview data revealed that awareness of deficit and thinking about psychological states can be present. However, the awareness of deficit may not be "online" and effectively integrated into decision-making. Without this online awareness of deficit the ability to appreciate or use and weigh information in the process of deciding some matters appeared absent. We argue that the decision-making abilities discussed are: (1) necessary for DMC, (2) threatened by ABI , and (3) assessable at interview. Some advice for practically incorporating these abilities within assessments of DMC in patients with OPD is outlined.

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.

Optimising and evaluating the characteristics of a multiple antigen ELISA for detection of Mycobacterium bovis infection in a badger vaccine field trial.

A long-term research programme has been underway in Ireland to evaluate the usefulness of badger vaccination as part of the national bTB (bovine tuberculosis) control strategy. This culminated in a field trial which commenced in county Kilkenny in 2009 to determine the effects of badger vaccination on Mycobacterium bovis transmission in badgers under field conditions. In the present study, we sought to optimise the characteristics of a multiplex chemiluminescent assay for detection of M. bovis infection in live badgers. Our goal was to maximise specificity, and therefore statistical power, during evaluation of the badger vaccine trial data. In addition, we also aimed to explore the effects of vaccination on test characteristics. For the test optimisation, we ran a stepwise logistic regression with analytical weights on the converted Relative Light Units (RLU) obtained from testing blood samples from 215 badgers captured as part of culling operations by the national Department of Agriculture, Food and the Marine (DAFM). The optimised test was applied to two other datasets obtained from two captive badger studies (Study 1 and Study 2), and the sensitivity and specificity of the test was attained separately for vaccinated and non-vaccinated badgers. During optimisation, test sensitivity was maximised (30.77%), while retaining specificity at 99.99%. When the optimised test was then applied to the captive badger studies data, we observed that test characteristics did not vary greatly between vaccinated and non-vaccinated badgers. However, a different time lag between infection and a positive test result was observed in vaccinated and non-vaccinated badgers. We propose that the optimized multiplex immunoassay be used to analyse the vaccine trial data. In relation to the difference in the time lag observed for vaccinated and non-vaccinated badgers, we also present a strategy to enable the test to be used during trial evaluation.

Making valid causal inferences from observational data.

The ability to make strong causal inferences, based on data derived from outside of the laboratory, is largely restricted to data arising from well-designed randomized control trials. Nonetheless, a number of methods have been developed to improve our ability to make valid causal inferences from data arising from observational studies. In this paper, I review concepts of causation as a background to counterfactual causal ideas; the latter ideas are central to much of current causal theory. Confounding greatly constrains causal inferences in all observational studies. Confounding is a biased measure of effect that results when one or more variables, that are both antecedent to the exposure and associated with the outcome, are differentially distributed between the exposed and non-exposed groups. Historically, the most common approach to control confounding has been multivariable modeling; however, the limitations of this approach are discussed. My suggestions for improving causal inferences include asking better questions (relates to counterfactual ideas and "thought" trials); improving study design through the use of forward projection; and using propensity scores to identify potential confounders and enhance exchangeability, prior to seeing the outcome data. If time-dependent confounders are present (as they are in many longitudinal studies), more-advanced methods such as marginal structural models need to be implemented. Tutorials and examples are cited where possible.

Decision-making capacity for treatment in psychiatric and medical in-patients: cross-sectional, comparative study.

BACKGROUND: Is the nature of decision-making capacity (DMC) for treatment significantly different in medical and psychiatric patients? AIMS: To compare the abilities relevant to DMC for treatment in medical and psychiatric patients who are able to communicate a treatment choice. METHOD: A secondary analysis of two cross-sectional studies of consecutive admissions: 125 to a psychiatric hospital and 164 to a medical hospital. The MacArthur Competence Assessment Tool - Treatment and a clinical interview were used to assess decision-making abilities (understanding, appreciating and reasoning) and judgements of DMC. We limited analysis to patients able to express a choice about treatment and stratified the analysis by low and high understanding ability. RESULTS: Most people scoring low on understanding were judged to lack DMC and there was no difference by hospital (P = 0.14). In both hospitals there were patients who were able to understand yet lacked DMC (39% psychiatric v. 13% medical in-patients, P<0.001). Appreciation was a better 'test' of DMC in the psychiatric hospital (where psychotic and severe affective disorders predominated) (P<0.001), whereas reasoning was a better test of DMC in the medical hospital (where cognitive impairment was common) (P = 0.02). CONCLUSIONS: Among those with good understanding, the appreciation ability had more salience to DMC for treatment in a psychiatric setting and the reasoning ability had more salience in a medical setting.

Coexistence of Huntington's disease and amyotrophic lateral sclerosis: a clinicopathologic study.

We report a retrospective case series of four patients with genetically confirmed Huntington's disease (HD) and sporadic amyotrophic lateral sclerosis (ALS), examining the brain and spinal cord in two cases. Neuropathological assessment included a polyglutamine recruitment method to detect sites of active polyglutamine aggregation, and biochemical and immunohistochemical assessment of TDP-43 pathology. The clinical sequence of HD and ALS varied, with the onset of ALS occurring after the mid-50's in all cases. Neuropathologic features of HD and ALS coexisted in both cases examined pathologically: neuronal loss and gliosis in the neostriatum and upper and lower motor neurons, with Bunina bodies and ubiquitin-immunoreactive skein-like inclusions in remaining lower motor neurons. One case showed relatively early HD pathology while the other was advanced. Expanded polyglutamine-immunoreactive inclusions and TDP-43-immunoreactive inclusions were widespread in many regions of the CNS, including the motor cortex and spinal anterior horn. Although these two different proteinaceous inclusions coexisted in a small number of neurons, the two proteins did not co-localize within inclusions. The regional distribution of TDP-43-immunoreactive inclusions in the cerebral cortex partly overlapped with that of expanded polyglutamine-immunoreactive inclusions. In the one case examined by TDP-43 immunoblotting, similar TDP-43 isoforms were observed as in ALS. Our findings suggest the possibility that a rare subset of older HD patients is prone to develop features of ALS with an atypical TDP-43 distribution that resembles that of aggregated mutant huntingtin. Age-dependent neuronal dysfunction induced by mutant polyglutamine protein expression may contribute to later-life development of TDP-43 associated motor neuron disease in a small subset of patients with HD.