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The great conducting teacher Hans Swarowsky told his students at Vienna’s Academy of Music and Performing Arts that a conductor has only three jobs: start the piece, make any changes within it, and finish it. Indeed, certain elements of time keeping would seem to render that task in conducting rather simple.
The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.
As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.
Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.
Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.
The U.S. led the world in environmental policy in the 1970s, but now lags behind comparable nations and resists joining others in tackling climate change. Two embedded, entwined, and exceptional American institutions—broad private property rights and competitive federalism—are necessary for explaining this shift. These two institutions shaped the exceptional stringency of 1970s American environmental laws and the powerful backlash against these laws that continues today. American colonies ensured broad private rights to use land and natural resources for profit. The colonies and the independent state governments that followed wielded expansive authority to govern this commodified environment. In the 1780s, Congress underwrote state governance of the privatized environment by directing the parceling and transfer of federal land to private parties and of environmental governance to future states. The 1787 Constitution cemented these relationships and exposed states to interstate economic competition. Environmental laws of the 1970s imposed unprecedented challenges to the environmental prerogatives long protected by these institutions, and the beneficiaries responded with a wide-ranging counterattack. Federalism enabled this opposition to build powerful regional alliances to stymie action on climate change. These overlooked institutional factors are necessary to explain why Canadian and American environmental policies have diverged.
Complex challenges may arise when patients present to emergency services with an advance decision to refuse life-saving treatment following suicidal behaviour.
To investigate the use of advance decisions to refuse treatment in the context of suicidal behaviour from the perspective of clinicians and people with lived experience of self-harm and/or psychiatric services.
Forty-one participants aged 18 or over from hospital services (emergency departments, liaison psychiatry and ambulance services) and groups of individuals with experience of psychiatric services and/or self-harm were recruited to six focus groups in a multisite study in England. Data were collected in 2016 using a structured topic guide and included a fictional vignette. They were analysed using thematic framework analysis.
Advance decisions to refuse treatment for suicidal behaviour were contentious across groups. Three main themes emerged from the data: (a) they may enhance patient autonomy and aid clarity in acute emergencies, but also create legal and ethical uncertainty over treatment following self-harm; (b) they are anxiety provoking for clinicians; and (c) in practice, there are challenges in validation (for example, validating the patient’s mental capacity at the time of writing), time constraints and significant legal/ethical complexities.
The potential for patients to refuse life-saving treatment following suicidal behaviour in a legal document was challenging and anxiety provoking for participants. Clinicians should act with caution given the potential for recovery and fluctuations in suicidal ideation. Currently, advance decisions to refuse treatment have questionable use in the context of suicidal behaviour given the challenges in validation. Discussion and further patient research are needed in this area.
Declaration of interest
D.G., K.H. and N.K. are members of the Department of Health's (England) National Suicide Prevention Advisory Group. N.K. chaired the National Institute for Health and Care Excellence (NICE) guideline development group for the longer-term management of self-harm and the NICE Topic Expert Group (which developed the quality standards for self-harm services). He is currently chair of the updated NICE guideline for Depression. K.H. and D.G. are NIHR Senior Investigators. K.H. is also supported by the Oxford Health NHS Foundation Trust and N.K. by the Greater Manchester Mental Health NHS Foundation Trust.
Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293–301)
OBJECTIVES/SPECIFIC AIMS: To describe adverse behavioral symptoms attributed to droxidopa therapy for neurogenic orthostatic hypotension (nOH). METHODS/STUDY POPULATION: BACKGROUND: Droxidopa, a norepinephrine (NE) precursor, improves symptoms of nOH by replenishing NE levels. Central NE effects are poorly described but may offer potential benefits given the pathophysiologic progression of α-synuclein-related disorders. Here we report a series of cognitive and behavioral side effects linked to droxidopa therapy. METHODS: We identified 5 patients treated at Vanderbilt University who developed behavioral symptoms including mania, irritability, and disorientation shortly after the initiation of droxidopa for nOH. Comprehensive chart reviews were performed for all patients, including analysis of droxidopa titration schedule and dosing, medical comorbidities, clinical course, and outcome. All patients had symptoms of synucleinopathy, manifesting with autonomic failure, REM behavior disorder, and parkinsonism. Four met criteria for idiopathic PD, and one was diagnosed with pure autonomic failure but had concomitant symptoms of parkinsonism and REM sleep behavior disorder. RESULTS/ANTICIPATED RESULTS: Our patients had no significant cognitive or behavioral symptoms before the initiation of droxidopa. The average decrease in blood pressure upon standing was 27 mmHg systolic and 17 mmHg diastolic. Behavioral disturbances were observed early in the titration period and at relatively low doses of droxidopa (total daily doses ranging from 300 to 800 mg/day; droxidopa therapeutic dose range 900–1800 mg/d). The most common symptoms reported were mania, irritability, and confusion. Symptoms resolved with dose reduction in 4 patients, and droxidopa was discontinued in 1 patient due to persistent irritability. No other medical comorbidities or alternative etiologies were identified to explain these effects. DISCUSSION/SIGNIFICANCE OF IMPACT: Droxidopa is a prodrug designed to act peripherally, but may also have important, yet poorly described, central effects. We hypothesize that these behavioral manifestations result from an “overdose” of key NE networks linking orbitofrontal and mesolimbic regions. Further studies are warranted to better characterize central NE effects in patients treated with droxidopa.
The correlation between ATP concentration and bacterial burden in the patient care environment was assessed. These findings suggest that a correlation exists between ATP concentration and bacterial burden, and they generally support ATP technology manufacturer-recommended cutoff values. Despite relatively modest discriminative ability, this technology may serve as a useful proxy for cleanliness.
Consider a product system over the positive cone of a quasi-lattice ordered group. We construct a Fell bundle over an associated groupoid so that the cross-sectional algebra of the bundle is isomorphic to the Nica–Toeplitz algebra of the product system. Under the additional hypothesis that the left actions in the product system are implemented by injective homomorphisms, we show that the cross-sectional algebra of the restriction of the bundle to a natural boundary subgroupoid coincides with the Cuntz–Nica–Pimsner algebra of the product system. We apply these results to improve on existing sufficient conditions for nuclearity of the Nica–Toeplitz algebra and the Cuntz–Nica–Pimsner algebra, and for the Cuntz–Nica–Pimsner algebra to coincide with its co-universal quotient.
Since 1998 archaeological investigations on Holme-next-the-Sea beach have recorded the waterlogged remains of two Bronze Age timber circles, timber structures, coppiced trees, metal objects, and salt- and freshwater marshes. The second timber circle (Holme II) is only the third waterlogged structure of its type to be discovered in Britain and only the second to be dated by dendrochronology. The felling of timbers used in Holme II has been dated to the spring or summer of 2049 bc, exactly the time as the felling of the timbers used to build the first circle (Holme I). This shared date provides the only known example of two adjacent monuments constructed at precisely the same time in British prehistory. It also informs comparisons between Holme II and other British timber circles and therefore helps develop interpretations. This paper suggests Holme II was a mortuary monument directly related to the use of Holme I.
Advances in hieroglyphic decipherment and in language contact typology provide new data and theories with which to investigate and reassess prior interpretations of Mayan linguistic history. The present study considers the shift from proto-Mayan *k and *k' to /ch/ and /ch'/, a sound change that affected several Mayan languages in different phonological contexts. This sound change, with a very particular set of conditions, has been highlighted as a defining feature of the Cholan-Tseltalan branch of the Mayan language family. New evidence suggests that this sound change was shared as a result of contact around the time of the Classic period, rather than reflecting an inherited sound change that would have taken place at a much earlier stage of the language family. Hieroglyphic data provide further evidence that this sound change was adopted in the hieroglyphic language in a word-by-word fashion, rather than applying to all similar phonological contexts at the same time.
Background: Few data are available on the neuropsychological, behavioural, or structural brain imaging outcomes in adolescents who underwent corrective surgery in infancy for tetralogy of Fallot. Methods: In this single-centre cross-sectional study, we enrolled 91 adolescents (13–16 years old) with tetralogy of Fallot and 87 referent subjects. Assessments included tests of academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition, as well as brain magnetic resonance imaging. Results: Genetic abnormalities or syndromes were present in 25% of tetralogy of Fallot patients, who had markedly greater neuropsychological morbidities than did patients without a syndrome. However, even patients without a syndrome performed significantly worse than the referent group or population norms in all of the neuropsychological domains assessed. In multivariable regression in those without a genetic/phenotypic syndrome, the strongest predictors of adverse late neurodevelopmental outcomes included a greater number of complications at the first operation, more total surgical complications across all operations, and occurrence of post-operative seizures. The presence of at least one abnormality on structural magnetic resonance imaging was more frequent in tetralogy of Fallot patients than the referent group (42% versus 8%). Conclusions: Adolescents with tetralogy of Fallot are at increased neurodevelopmental risk and would benefit from ongoing surveillance and educational supports even after childhood.