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Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke.
We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery.
We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone.
Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%.
The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
The digitization of African materials has made it easier than ever for students to engage with primary source documentation and undertake original research. Digitizing sources and using digital sources to teach African history has great pedagogical value, but must be done ethically. This article suggests a model for collaborative and publicly-engaged scholarship, demonstrating the potential of transnational projects and shared knowledge production while maintaining sensitivity towards questions of the hegemony of the North. The study draws on experience of a virtual internship project between North American-based university students and the South African non-profit South African History Online (SAHO).
The study examined (a) whether alcohol use subgroups could be identified among African Americans assessed from adolescence through early adulthood, and (b) whether subgroup membership was associated with the interaction between internalizing symptoms and antisocial behavior polygenic risk scores (PRSs) and environmental characteristics (i.e., parental monitoring, community disadvantage). Participants (N = 436) were initially recruited for an elementary school-based prevention trial in a Mid-Atlantic city. Youths reported on the frequency of their past year alcohol use from ages 14–26. DNA was obtained from participants at age 21. Internalizing symptoms and antisocial behavior PRSs were created based on a genome-wide association study (GWAS) conducted by Benke et al. (2014) and Tielbeek et al. (2017), respectively. Parental monitoring and community disadvantage were assessed at age 12. Four classes of past year alcohol use were identified: (a) early-onset, increasing; (b) late-onset, moderate use; (c) low steady; and (d) early-onset, decreasing. In high community disadvantaged settings, participants with a higher internalizing symptoms PRS were more likely to be in the early-onset, decreasing class than the low steady class. When exposed to elevated community disadvantage, participants with a higher antisocial behavior PRS were more likely to be in the early-onset, increasing class than the early-onset, decreasing and late-onset, moderate use classes.
Postmortem human brain studies provide the molecular, cellular, and circuitry levels of resolution essential for the development of mechanistically-novel interventions for cognitive deficits in schizophrenia. However, the absence of measures of premortem cognitive aptitude in postmortem subjects has presented a major challenge to interpreting the relationship between the severity of neural alterations and cognitive deficits within the same subjects.
To begin addressing this challenge, proxy measures of cognitive aptitude were evaluated in postmortem subjects (N = 507) meeting criteria for schizophrenia, major depressive or bipolar disorder, and unaffected comparison subjects. Specifically, highest levels of educational and occupational attainment of the decedent and their parents were obtained during postmortem psychological autopsies.
Consistent with prior findings in living subjects, subjects with schizophrenia had the lowest educational and occupational attainment relative to all other subject groups, and they also failed to show the generational improvement in attainment observed in all other subject groups.
Educational and occupational attainment data obtained during postmortem psychological autopsies can be used as proxy measures of premortem cognitive function to interrogate the neural substrate of cognitive dysfunction in schizophrenia.
Understanding which characteristics of persons with dementia (PWD) and their caregivers are associated with unmet needs can inform strategies to address those needs. Our purpose was to determine the percentage of PWD having unmet needs and significant correlates of unmet needs in PWD.
Cross-sectional data were analyzed using bivariate and hierarchical multiple linear regression analyses.
Participants lived in the greater Baltimore, Maryland and Washington DC suburban area.
A sample of 646 community-living PWD and their informal caregivers participated in an in-home assessment of dementia-related needs.
Unmet needs were identified using the Johns Hopkins Dementia Care Needs Assessment. Correlates of unmet needs were determined using demographic, socioeconomic, clinical, functional and quality of life characteristics of the PWD and their caregivers.
PWD had a mean of 10.6 (±4.8) unmet needs out of 43 items (24.8%). Unmet needs were most common in Home/Personal Safety (97.4%), General Health Care (83.1%), and Daily Activities (73.2%) domains. Higher unmet needs were significantly related to non-white race, lower education, higher cognitive function, more neuropsychiatric symptoms, lower quality of life in PWD, and having caregivers with lower education or who spent fewer hours/week with the PWD.
Unmet needs are common in community-living PWD, and most are non-medical. Home-based dementia care can identify and address PWD’s unmet needs by focusing on care recipients and caregivers to enable PWD to remain safely at home.
Plant invasions can have large effects on ecosystem services. Some plant invaders were introduced specifically to restore key services to ecosystems, and other invaders are having unintended, detrimental effects on services, such as the quantity and quality of water delivered, flood control, erosion control, and food production. Many ecosystem services are difficult to measure directly, and although there are extensive studies on plant invaders and ecosystem processes, a number of challenges prevent us from confidently extrapolating those processes as proxies for services. To extrapolate local, short-term measures of processes to ecosystem services, we must: (1) determine which processes are the key contributors to a service, (2) assess how multiple processes interact to provide a given service, (3) determine how vegetation types and species affect those processes, and (4) explicitly assess how ecosystem services and their controls vary over space and time, including reliance of ecosystem services on “hot spots” and “hot moments” and a minimum size of a vegetation type in the landscape. A given invader can have positive effects on some services and negative effects on others. It is important to consider that, in some systems, shifting environmental conditions may no longer support native species and that invasive species may be critical contributors to the resilience of ecosystem services.
There is little disagreement among the stakeholders in the pharmaceutical industry and other discovery and development establishments about the existence of a crisis in research and development (R&D) productivity. There are mounting concerns about the difficulty of securing regulatory approval, the recent spates of late-stage failures to lack of efficacy, the withdrawal of drugs after commercialization because of safety concerns, the threat of generic substitution, and complaints over the prices of new medicines. Each of these concerns, and the corresponding societal, political, academic, and industrial responses, will have significant implications for the vitality and sustainability of the pharmaceutical industry and other similar establishments. These implications, in turn, will affect our ability to capitalize on new advances in biomedical knowledge and to develop innovations in diagnostic tools, therapeutic interventions, and preventive treatment.
Although there is agreement on the challenges, reaching consensus on the solution is much more difficult. Each functional area in the drug development enterprise has engaged in a variety of initiatives to increase productivity and reduce costs, ranging from deploying new technology and enhancing the information technology (IT) infrastructure to outsourcing and relocating overseas. Although many of these initiatives have merit, it is becoming clearer that more radical changes are necessary. In particular, the central process of knowledge generation has come under scrutiny along with the strategic and governance aspects of the decision-making process.
Transcriptomic studies are useful for elucidating molecular mechanisms through which changes in nutrient availability produce pleiotropic effects on whole-body and tissue physiology. To further the knowledge of gene-regulatory effects of Zn on tissues important for adult and fetal Zn nutrition, we analysed the responses of human intestinal Caco-2 and placental JAR cells to changes in Zn supply. Analysis of oligonucleotide microarrays demonstrated that, despite the analogous roles of the two tissues in nutrient transfer, different genes respond to changes in Zn availability in intestinal cells compared with placental cells. A number of Fe- and Cu-related genes were identified as targets for regulation by Zn, revealing potential mechanisms underlying reported dietary interactions between Zn and other metals. We established that there are fundamental differences in Zn-regulated transcriptional control in Caco-2 compared with JAR cells. We demonstrated that Zn-induced transcriptional activation of the metallothionein 2A promoter occurs over different, and physiologically relevant, concentration ranges in Caco-2 and JAR cells, indicating that these cell lines sense changes in the extracellular Zn concentration over different ranges. Also, we established that mRNA levels of the Zn-responsive metal response element binding transcription factor (MTF)-1, and its homologue MTF-2, are regulated by Zn in Caco-2 but not JAR cells, which may in part underlie differential gene responses to Zn in intestinal and placental cells. The present study identified a number of novel molecular targets that may underlie symptoms associated with deficient or excessive Zn supply and highlighted the necessity of taking account of cell- and tissue-specific processes when investigating Zn-regulated gene expression in mammals.
A history of exposure to harsh physical discipline has been linked to
negative outcomes for children, ranging from conduct disorder to
depression and low self-esteem. The present study extends this work into
adolescence, and examines the relationship of lifetime histories of harsh
discipline to adolescents' internalizing and externalizing symptoms
and to their developing capacities for establishing autonomy and
relatedness in family interactions. Adolescent and parent reports of harsh
discipline, independently coded observations of conflictual interactions,
and adolescent reports of symptoms were obtained for 141 adolescents at
age 16. Both parents' use of harsh discipline was related to greater
adolescent depression and externalizing behavior, even when these effects
were examined over and above the effects of other parenting measures known
to account for these symptoms. Adolescents exposed to harsh discipline
from mothers were also less likely to appear warm and engaged during an
interaction task with their mothers. It is suggested that a history of
harsh discipline is associated not only with social and emotional
functioning, but also with the developmental task of autonomy and
relatedness.This study and its write-up
were supported by grants from the National Institute of Mental Health
(R01-MH44934 and R01-MH58066).
Amnestic mild cognitive impairment (aMCI) represents a high-risk
factor for Alzheimer's disease (AD) and is characterized by a
selective decline in episodic memory. Although by definition aMCI is not
associated with impaired verbal fluency performance, we examined relative
differences between fluency tasks because AD is characterized by poorer
semantic than phonemic fluency. Phonemic and semantic fluency trials were
administered to 46 healthy controls, 33 patients with aMCI, and 33
patients with AD. Results revealed a progressive advantage (controls >
aMCI > AD) in semantic, relative to phonemic fluency. Difference scores
between tasks distinguished each group from the others with medium to
large effect sizes (d) ranging from 0.49 to 1.07. Semantic
fluency relies more on semantic associations between category exemplars
than does phonemic fluency. This aMCI fluency pattern reflects degradation
of semantic networks demonstrating that initial neuropathology may extend
beyond known early changes in hippocampal regions. (JINS, 2006,
12, 570–574.)The data were
collected in accordance with the guidelines of the Helsinki Declaration
and approved by the Research Ethics and Scientific Review Committee of
Baycrest Centre. This is an original submission. Portions of these data
were presented at the annual meeting of the International
Neuropsychological Society, February 2005, St. Louis, Missouri. There is
no conflict of interest.