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Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
The national response to the COVID-19 pandemic has highlighted critical weaknesses in domestic health care and public health emergency preparedness despite nearly two decades of federal funding for multiple programs designed to encourage cross-cutting collaboration in emergency response. Health care coalitions (HCCs), which are funded through the Hospital Preparedness Program, were first piloted in 2007 and have been continuously funded nationwide since 2012 to support broad collaborations across public health, emergency management, emergency medical services, and the emergency response arms of the health care system within a geographical area. This commentary provides a SWOT analysis to summarize the strengths, weaknesses, opportunities, and threats related to the current HCC model against the backdrop of COVID-19. We close with concrete recommendations for better leveraging the HCC model for improved health care system readiness. These include better evaluating the role of HCCs and their members (including the responsibility of the HCC to better communicate and align with other sectors), reconsidering the existing framework for HCC administration, increasing incentives for meaningful community participation in HCC preparedness, and supporting next-generation development of health care preparedness systems for future pandemics.
The purpose of this study was to demonstrate the use of social network analysis to understand public discourse on Twitter around the novel coronavirus disease 2019 (COVID-19) pandemic. We examined different network properties that might affect the successful dissemination by and adoption of public health messages from public health officials and health agencies.
We focused on conversations on Twitter during 3 key communication events from late January to early June of 2020. We used Netlytic, a Web-based software that collects publicly available data from social media sites such as Twitter.
We found that the network of conversations around COVID-19 is highly decentralized, fragmented, and loosely connected; these characteristics can hinder the successful dissemination of public health messages in a network. Competing conversations and misinformation can hamper risk communication efforts in a way that imperil public health.
Looking at basic metrics might create a misleading picture of the effectiveness of risk communication efforts on social media if not analyzed within the context of the larger network. Social network analysis of conversations on social media should be an integral part of how public health officials and agencies plan, monitor, and evaluate risk communication efforts.
The lack of radiation knowledge among the general public continues to be a challenge for building communities prepared for radiological emergencies. This study applied a multi-criteria decision analysis (MCDA) to the results of an expert survey to identify priority risk reduction messages and challenges to increasing community radiological emergency preparedness.
Professionals with expertise in radiological emergency preparedness, state/local health and emergency management officials, and journalists/journalism academics were surveyed following a purposive sampling methodology. An MCDA was used to weight criteria of importance in a radiological emergency, and the weighted criteria were applied to topics such as sheltering-in-place, decontamination, and use of potassium iodide. Results were reviewed by respondent group and in aggregate.
Sheltering-in-place and evacuation plans were identified as the most important risk reduction measures to communicate to the public. Possible communication challenges during a radiological emergency included access to accurate information; low levels of public trust; public knowledge about radiation; and communications infrastructure failures.
Future assessments for community readiness for a radiological emergency should include questions about sheltering-in-place and evacuation plans to inform risk communication.
OBJECTIVES/GOALS: Vaginal ring delivery of antiretroviral drugs may provide protection against acquisition of HIV-1 when used as pre-exposure prophylaxis. As part of a randomized placebo-controlled safety trial of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR), we assessed product acceptability through surveys of 17 women after continuous ring use. METHODS/STUDY POPULATION: Sexually active, HIV negative women between the ages of 18 and 45 were enrolled to investigate the safety and pharmacokinetics of three months of continuous TDF IVR use. The study was designed to include 40 US participants randomly assigned (3:1) to a TDF or placebo IVR. Twelve were randomized to TDF and five were assigned to the placebo group before the study was electively discontinued due to development of vaginal ulcerations in eight women in the TDF group. Acceptability data regarding TDF and placebo ring use was gathered via self-administered, computer-based questionnaires at the one- and three-month study visits. Participants were asked about overall attitudes and feelings regarding the TDF and placebo IVR, vaginal changes associated with ring use, and their experiences with ring use during menses and with sex. RESULTS/ANTICIPATED RESULTS: The mean age of participants was 30 years (range 18 - 42). Sixteen of 17 (94%) participants completed all study questions at both visits. When asked about ring likeability at one-month, 12 of 16 (75%) women reported overall liking the ring, including 5 of 8 (63%) who developed ulcerations. Vaginal changes described during ring use included 8 participants who indicated that the “vagina was wetter” and 2 who reported that the “vagina was drier.” Additionally, 10 of 12 (83%) who had their period during the first month of the study were not bothered by ring use during menses, and 11 of 16 (69%) stated that the ring was not bothersome with use during sex. When asked at the three-month visit, most reported that they would prefer to wear the ring rather than use a condom during sex, however, condom use was low at baseline in this population. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite unanticipated ulcers, the IVRs were acceptable, especially when used with menses and during sex. Regardless of the group assigned or vaginal changes experienced, and even amongst those who developed ulcerations, the women had positive attitudes towards the ring, which is promising for future use of vaginal rings as a method for HIV prevention.
The otoliths (ear stones) of fishes are commonly used to describe the age and growth of marine and freshwater fishes. These non-skeletal structures are fortuitous in their utility by being composed of mostly inorganic carbonate that is inert through the life of the fish. This conserved record functions like an environmental chronometer and bomb-produced radiocarbon (14C)—a 14C signal created by atmospheric testing of thermonuclear devices—can be used as a time-specific marker in validating fish age. However, complications from the hydrogeology of nearshore marine environments can complicate 14C levels, as was the case with gray snapper (Lutjanus griseus) along the Gulf of Mexico coast of Florida. Radiocarbon of these nearshore waters is influenced by freshwater input from the karst topography of the Upper Floridan Aquifer—estuarine waters that are 14C-depleted from surface and groundwater inputs. Some gray snapper likely recruited to this kind of environment where 14C levels were depleted in the earliest otolith growth, although age was validated for individuals that were not exposed to 14C-depleted waters to an age of at least 25 years with support for a 30-year lifespan.
Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD).
A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function.
Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline.
These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.
The effects of long-term antipsychotic medication on cognition in schizophrenia are unclear (Husa A.P. et al., Schizophr. Res. 2014).
Understanding how long-term antipsychotic treatment affects cognition is crucial for the development of safe, evidence-based treatment of schizophrenia.
To analyse the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia at age 43 years in a general population sample.
Sixty (33 males) schizophrenia spectrum subjects from the Northern Finland Birth Cohort 1966 were assessed at age 43 years by California Verbal Learning Test, Visual Object Learning Test, Abstraction Inhibition and Working Memory task, Verbal fluency, Visual series, Vocabulary, Digit Span and Matrix reasoning. Cumulative lifetime antipsychotic dose-years were collected from treatment records and interviews. A factor analysis based on the cognitive tests resulted in one cognitive factor. The association between this cognitive composite score and antipsychotic dose-years was analysed by linear regression.
Higher lifetime antipsychotic dose-years were statistically significantly associated with poorer cognitive composite score at age 43 years (B=-0.32, p>0.001), also when adjusted for gender, onset age, remission and number of hospital treatment days (B=-0.42, p=0.008).
To our knowledge, this is the first report of an association between cumulative lifetime antipsychotic dose and cognition in midlife in schizophrenia. Based on this data, the use of high antipsychotic doses may relate to poorer cognitive functioning in schizophrenia after twenty years of illness. These results do not support the view that antipsychotics prevent cognitive decline or promote cognitive recovery in schizophrenia.
Cognitive deficits, such as verbal memory dysfunction, are a core feature of schizophrenia. Yet the longitudinal course and associations of cognitive deficits with antipsychotic medication remain unclear.
Our aim was to analyze how lifetime antipsychotic dosage associates with the change of verbal learning and memory in individuals with schizophrenia during a 9-year follow-up.
Forty-two subjects with schizophrenic psychoses (22 males) from the Northern Finland 1966 Birth Cohort went through diagnostic interviews and cognitive assessment including California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data of the subjects’ lifetime antipsychotic doses in chlorpromazine equivalents were collected from patient history records, interviews and national registers. The association between verbal learning and memory (immediate free recall of trials 1-5 and free recall after long delay) and dose-years of antipsychotics was analyzed by logistic regression model.
Higher dose-years of any and typical antipsychotics, but not atypical antipsychotics, associated statistically significantly to worse verbal learning and memory in cross-sectional analyses at age 34 years, even when onset age, sex, and severity of symptoms were controlled for. However, there was no statistically significant association between lifetime antipsychotic use and verbal learning and memory change between ages 34 and 43 years.
High lifetime antipsychotic dose did not associate to decrease in verbal learning and memory in schizophrenia in 9 years of follow-up. To our knowledge, this is a first report on association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up.
Patients with schizophrenia generally perform worse than control subjects on all cognitive domains, and particularly in memory functions. It is still unclear, how cognition changes during years of illness in schizophrenia.
Our aim was to analyze the change in verbal learning and memory functions in subjects with schizophrenia and healthy controls during a 9-year follow-up.
The sample was the general population based Northern Finland 1966 Birth Cohort. In 1999-2001 and in 2008-2010 field studies were performed, including repeated measures of clinical status and the California Verbal Learning Test (CVLT). CVLT was used for the estimation of the course of a possible change of verbal learning and memory during the follow-up. The sample included 41 individuals with schizophrenic psychoses and 74 non-psychotic controls.
Both cases and controls had statistically significant decline in measures of CVLT. However, the change in verbal learning and memory in the 9 -year follow-up was not statistically significantly different between cases and controls. Among cases, age of illness onset and sex had no statistically significant effect on change of verbal learning and memory.
According to our unselected, population based sample with long follow up, the impairments during the life span in verbal learning and memory in schizophrenia was not different compared to controls. These results imply that schizophrenia is not a progressing degenerative illness.
Since its 1960s origins, the Haddon matrix has served as a tool to understand and prevent diverse mechanisms of injuries and promote safety. Potential remains for broadened application and innovation of the matrix for disaster preparedness. Hospital functionality and efficiency are particularly important components of community vulnerability in developed and developing nations alike. Given the Haddon matrixʼs user-friendly approach to integrating current engineering concepts, behavioral sciences, and policy dimensions, we seek to apply it in the context of hospital earthquake preparedness and response. The matrixʼs framework lends itself to interdisciplinary planning and collaboration between social and physical sciences, paving the way for a systems-oriented reduction in vulnerabilities. Here, using an associative approach to integrate seemingly disparate social and physical science disciplines yields innovative insights about hospital disaster preparedness for earthquakes. We illustrate detailed examples of pre-event, event, and post-event engineering, behavioral science, and policy factors that hospital planners should evaluate given the complex nature, rapid onset, and broad variation in impact and outcomes of earthquakes. This novel contextual examination of the Haddon matrix can enhance critical infrastructure disaster preparedness across the epidemiologic triad, by integrating essential principles of behavioral sciences, policy, law, and engineering to earthquake preparedness.
Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia.
Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression.
Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition.
Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.
There are large between-country differences in measures of economic and noneconomic well-being. Many researchers view increasing the stock of human capital as the key to raising economic development, promoting democratization, and improving health, and hence improving overall societal well-being. The single most studied aspect of human capital concerns cognitive competence. Differences in population cognitive competence might explain these societal differences. Evidence suggests that education builds cognitive competence, and education and cognitive competence promote better social outcomes, in terms of both economic and noneconomic factors. However, measuring population cognitive competence for countries requires representative samples, culture-fair tests, equivalency in the relationship between test measures and other cognitive attributes, and comparability in testing situations. In most cases, none of this has been achieved.
) denote the number of odd-balanced unimodal sequences of size
with even parts congruent to
) and odd parts at most half the peak. We prove that two-variable generating functions for
are simultaneously quantum Jacobi forms and mock Jacobi forms. These odd-balanced unimodal rank generating functions are also duals to partial theta functions originally studied by Ramanujan. Our results also show that there is a single
to which the errors to modularity of these two different functions extend. We also exploit the quantum Jacobi properties of these generating functions to show, when viewed as functions of the two variables
, how they can be expressed as the same simple Laurent polynomial when evaluated at pairs of roots of unity. Finally, we make a conjecture which fully characterizes the parity of the number of odd-balanced unimodal sequences of size
with even parts congruent to
and odd parts at most half the peak.
The study of white dwarfs, the end stage of stellar evolution for more than 95% of stars, is critical to bettering our understanding of the late stages of the lives of low mass stars. In particular, the post main sequence evolution of binary star systems is complex, and the identification and analysis of double degenerate systems is a crucial step in constraining models of binary star systems. Binary white dwarfs in open star clusters are particularly useful because cluster parameters such as distance, metal content, and total system age are more tightly constrained than for field double degenerates. Here we use the precision astrometry from the Gaia Data Release 2 catalog to study two other white dwarfs which were identified as candidate double degenerates in the field of the open star cluster NGC 6633. One of the two objects, LAWDS 4, is found to have astrometric properties fully consistent with that of the cluster. In such a case, the object is significantly overluminous for a single white dwarf, strongly indicating binarity. The second candidate binary, LAWDS 7, appears to be inconsistent with cluster membership, though a more thorough analysis is necessary to properly quantify the probability. At present we are proceeding to model the photometric and spectroscopic data for both objects as if they were cluster member double degenerates. Results of this latter analysis are forthcoming. Our results will add crucial data to the study of binary star evolution in open star clusters.
Network representations of systems from various scientific and societal domains are neither completely random nor fully regular, but instead appear to contain recurring structural features. These features tend to be shared by networks belonging to the same broad class, such as the class of social networks or the class of biological networks. Within each such class, networks describing similar systems tend to have similar features. This occurs presumably because networks representing similar systems would be expected to be generated by a shared set of domain-specific mechanisms, and it should therefore be possible to classify networks based on their features at various structural levels. Here we describe and demonstrate a new hybrid approach that combines manual selection of network features of potential interest with existing automated classification methods. In particular, selecting well-known network features that have been studied extensively in social network analysis and network science literature, and then classifying networks on the basis of these features using methods such as random forest, which is known to handle the type of feature collinearity that arises in this setting, we find that our approach is able to achieve both higher accuracy and greater interpretability in shorter computation time than other methods.
To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.
Memory clinics and dementia services.
Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).
Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.
There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).
There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.
To characterise subjective symptoms in patients undergoing surgical repair of superior semicircular canal dehiscence.
Questionnaires assessing symptom severity and impact on function and quality of life were administered to patients before superior semicircular canal dehiscence surgery, between June 2011 and March 2016. Questionnaire sections included general quality of life, internal amplified sounds, dizziness and tinnitus, with scores of 0–100 points.
Twenty-three patients completed the questionnaire before surgery. Section scores (mean±standard deviation) were: 38.2 ± 25.2 for general quality of life, 52.5 ± 23.9 for internal amplified sounds, 35.1 ± 28.8 for dizziness, 33.3 ± 30.7 for tinnitus, and 39.8 ± 22.2 for the composite score. Cronbach's α statistic averaged 0.93 (range, 0.84–0.97) across section scores, and 0.83 for the composite score.
The Gopen–Yang Superior Semicircular Canal Dehiscence Questionnaire provides a holistic, patient-centred characterisation of superior semicircular canal dehiscence symptoms. Internal consistency analysis validated the questionnaire and provided a quantitative framework for further optimisation in the clinical setting.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.