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Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.
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.
Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort.
Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis.
Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD.
MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.
Emergency medicine (EM) training programs incorporate simulation for teaching as well as formative and summative assessment. The development of a simulation curriculum for Canadian postgraduate EM programs is underway and would be facilitated by a standardized, user-friendly, nationally endorsed simulation template. We convened a nationally representative group of simulation educators to participate in a three-phase process to develop and refine a simulation case template for Canadian EM educators. Participants provided feedback by means of free text comments and focus groups which were analyzed to inform modification of the template. We anticipate that this template will facilitate the sharing of cases across sites and the development of standardized cases for simulation-based assessment.
The Emergency Medicine (EM) Specialty Committee of the Royal College of Physicians and Surgeons of Canada (RCPSC) specifies that resuscitation entrustable professional activities (EPAs) can be assessed in the workplace and simulated environments. However, limited validity evidence for these assessments in either setting exists. We sought to determine if EPA ratings improve over time and whether an association exists between ratings in the workplace v. simulation environment.
All Foundations EPA1 (F1) assessments were collected for first-year residents (n = 9) in our program during the 2018–2019 academic year. This EPA focuses on initiating and assisting in the resuscitation of critically ill patients. EPA ratings obtained in the workplace and simulation environments were compared using Lin's concordance correlation coefficient (CCC). To determine whether ratings in the two environments differed as residents progressed through training, a within-subjects analysis of variance was conducted with training environment and month as independent variables.
We collected 104 workplace and 36 simulation assessments. No correlation was observed between mean EPA ratings in the two environments (CCC(8) = -0.01; p = 0.93). Ratings in both settings improved significantly over time (F(2,16) = 18.8; p < 0.001; η2 = 0.70), from 2.9 ± 1.2 in months 1–4 to 3.5 ± 0.2 in months 9–12. Workplace ratings (3.4 ± 0.1) were consistently higher than simulation ratings (2.9 ± 0.2) (F(2,16) = 7.2; p = 0.028; η2 = 0.47).
No correlation was observed between EPA F1 ratings in the workplace v. simulation environments. Further studies are needed to clarify the conflicting results of our study with others and build an evidence base for the validity of EPA assessments in simulated and workplace environments.
To make a tentative assessment of the consumption of cassava in three countries in South-east Asia and the cyanogenic potential (CNp) of the crop as a possible food safety issue.
We used data from the Ministry of Health in Vietnam and Statistics Authorities in Indonesia and Philippines (mean household consumption per province) to assess cassava consumption. Conversions of units were needed to facilitate the comparison of cassava consumption between countries. The most up-to-date data available regarding both cassava consumption and the CNp of cassava grown in the respective countries were assessed.
Vietnam, Indonesia and Philippines.
Respondents from provinces in Vietnam (nineteen), Indonesia (thirty-three) and Philippines (eighty-one) were asked to complete a recall questionnaire detailing either the previous 24-h’ or the 7-d’ cassava consumption.
Among the three countries, available data indicated that the highest median cassava-consumption figures percapita were from Indonesia and the Philippines (9·01 and 7·28 g/capita per d, respectively), with Vietnam having the least (1·14 g/capita per d). Published information regarding the CNp of cassava in the three countries was limited.
While the findings of the present study are somewhat limited by a lack of available information regarding both the extent of cassava consumption and the CNp of cassava consumed in the three countries, it appears likely that cyanogen intake arising from cassava consumption among the three countries exceeds the FAO/WHO Provisional Maximum Tolerable Daily Intake, although any risk to public health appears limited to a minority of provinces in each country.
We agree that the emergence of cumulative technological culture was tied to nonsocial cognitive skills, namely, technical-reasoning skills, which allowed humans to constantly acquire and improve information. Our concern is with a reading of the history of cumulative technological culture that is based largely on modern experiments in simulated settings and less on phenomena crucial to the long-term dynamics of cultural evolution.
The rupture of atherosclerotic plaques is the prerequisite for adverse cardiovascular events. Calcification morphology plays a critical role in plaque stability, therefore accurate calcification classification is essential for favourable patient management. Blood biomarkers may be a worthwhile approach to stratify patients based on calcification phenotype. Vitamin K-dependent Matrix γ-carboxyglutamate (Gla) protein (MGP) is a potent inhibitor of vascular calcification. Recent studies have demonstrated the potential utility of circulating non-functional MGP (dp-ucMGP) measurements to determine arterial stiffness and calcification levels. The objective of this study was to examine the relationship between circulating dp-ucMGP and calcification phenotype within symptomatic atherosclerotic lesions. Consenting patients undergoing standard endarterectomy procedures were recruited (n = 29). Fasting venous blood was collected preoperatively. Circulating plasma levels of dp-ucMGP were quantified using the inaKtif MGP (dp-ucMGP) iSYS kit. A bicinchoninic acid assay was used to standardise the total protein content present in each sample. High-resolution micro-CT imaging was conducted on the excised atherosclerotic specimens postoperatively. ImageJ post-processing was used to accurately quantify the calcification volume (≥ 130 Hounsfield Units) and determine the total number of calcified particles (3D objects counter plugin). Thirteen carotid (average age 71 years, 9 male) and fourteen peripheral lower limb (average age 65 years, 12 male) patients were examined. One patient had a carotid and a peripheral lower limb plaque (age 79, male). Peripheral lower limb specimens have larger volumes of calcification and higher numbers of calcified particles than carotid samples (472 ± 310 vs 85 ± 113mm3, p < 0.0005; 13919 ± 16034 vs 3476 ± 6208, p = 0.061.) While a higher dp-ucMGP value was noted in carotid than peripheral lower limb patients (214 ± 52 vs 169 ± 36pmol/L, p = 0.014) there was no correlation between circulating dp-ucMGP and calcification volume or number of calcified particles (rs = -0.329 and rs = 0.046). Previous research also found that peripheral lower limb lesions contain higher volumes of calcification than carotid lesions. There is currently no published data on calcified particle comparisons. Patients with symptomatic carotid disease are assumed to have a degree of peripheral arterial disease, this could explain the higher levels of circulating dp-ucMGP in carotid patients. The current study did not examine the dietary patterns of individuals with regards to Vitamin K intake or analyse other areas of the vasculature for additional calcification. This may interfere with dp-ucMGP measurements. This study serves as a preliminary investigation into the potential of dp-ucMGP as a blood based biomarker to distinguish between symptomatic atherosclerotic calcification phenotypes.
Recent work has demonstrated that Goshen points overlap in time with another group of unfluted lanceolate points from the Plains, Plainview points. This has raised the question of whether the two types should be kept separate or consolidated into a single type. We sought to resolve this issue by applying geometric morphometric methods to a sample of points from well-documented Goshen and Plainview assemblages. We found that their shapes were statistically indistinguishable, which indicates that Goshen and Plainview points should be assigned to the same type. Because Plainview points were recognized before Goshen points, it is the latter type name that should be dropped. Sinking Goshen into Plainview allows us to move beyond taxonomic issues and toward understanding both the spatiotemporal variation that exists among Plainview assemblages and what it can tell us about the adaptations and social dynamics of Plainview groups.
Simulation plays an integral role in the Canadian healthcare system with applications in quality improvement, systems development, and medical education. High-quality, simulation-based research will ensure its effective use. This study sought to summarize simulation-based research activity and its facilitators and barriers, as well as establish priorities for simulation-based research in Canadian emergency medicine (EM).
Simulation-leads from Canadian departments or divisions of EM associated with a general FRCP-EM training program surveyed and documented active EM simulation-based research at their institutions and identified the perceived facilitators and barriers. Priorities for simulation-based research were generated by simulation-leads via a second survey; these were grouped into themes and finally endorsed by consensus during an in-person meeting of simulation leads. Priority themes were also reviewed by senior simulation educators.
Twenty simulation-leads representing all 14 invited institutions participated in the study between February and May, 2018. Sixty-two active, simulation-based research projects were identified (median per institution = 4.5, IQR 4), as well as six common facilitators and five barriers. Forty-nine priorities for simulation-based research were reported and summarized into eight themes: simulation in competency-based medical education, simulation for inter-professional learning, simulation for summative assessment, simulation for continuing professional development, national curricular development, best practices in simulation-based education, simulation-based education outcomes, and simulation as an investigative methodology.
This study summarized simulation-based research activity in EM in Canada, identified its perceived facilitators and barriers, and built national consensus on priority research themes. This represents the first step in the development of a simulation-based research agenda specific to Canadian EM.
Interstellar carbon has been detected in both gas-phase molecules and solid particles. The goal of this study is to identify the link between these two phases of cosmic carbon. Here we report preliminary results on the low temperature formation of carbonaceous dust grains from gas-phase aromatic hydrocarbon precursors. This is done using the supersonic expansion of an argon jet seeded with aromatic molecules and exposed to an electrical discharge. We report experimental evidence of efficient carbon dust condensation from aromatic molecules including benzene and naphthalene. The molecular content of the solid grains is probed with laser desorption mass spectrometry. The mass spectra reveal a rich molecular composition including fragments of the parent molecule but also growth into larger molecular species.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
It has long been assumed that Folsom points are more standardized than Clovis points, although an adequate test of this proposition has yet to be undertaken. Here, we address that deficiency by using data from a sample of Folsom and Clovis points recovered from sites across the western United States. We used geometric morphometric techniques to capture point shape and then conducted statistical analyses of variability associated with Clovis and Folsom point bases and blades. Our results demonstrate that Folsom bases and blades are less variable than those on earlier Clovis points, indicating an increase in point standardization during the Early Paleoindian period. In addition, despite published claims to the contrary, Clovis and Folsom point bases are no more variable than blades. Based on these results, we conducted additional analyses to examine the modularity and size of Clovis and Folsom points. The results suggest Clovis points have more integrated base and blade segments than Folsom points. We suggest that several classes of Clovis points—intended for different functions—might have been in use during the Clovis period and that the later Folsom points might have served only as weapon tips, the shape of which were constrained by the fluting process.
Rapid identification of esophageal intubations is critical to avoid patient morbidity and mortality. Continuous waveform capnography remains the gold standard for endotracheal tube (ETT) confirmation, but it has limitations. Point-of-care ultrasound (POCUS) may be a useful alternative for confirming ETT placement. The objective of this study was to determine the accuracy of paramedic-performed POCUS identification of esophageal intubations with and without ETT manipulation.
A prospective, observational study using a cadaver model was conducted. Local paramedics were recruited as subjects and each completed a survey of their demographics, employment history, intubation experience, and prior POCUS training. Subjects participated in a didactic session in which they learned POCUS identification of ETT location. During each study session, investigators randomly placed an ETT in either the trachea or esophagus of four cadavers, confirmed with direct laryngoscopy. Subjects then attempted to determine position using POCUS both without and with manipulation of the ETT. Manipulation of the tube was performed by twisting the tube. Descriptive statistics and logistic regression were used to assess the results and the effects of previous paramedic experience.
During 12 study sessions, from March 2014 through December 2015, 57 subjects participated, evaluating a total of 228 intubations: 113 tracheal and 115 esophageal. Subjects were 84.0% male, mean age of 39 years (range: 22 - 62 years), with median experience of seven years (range: 0.6 - 39 years). Paramedics correctly identified ETT location in 158 (69.3%) cases without and 194 (85.1%) with ETT manipulation. The sensitivity and specificity of identifying esophageal location without ETT manipulation increased from 52.2% (95% confidence interval [CI], 43.0-61.0) and 86.7% (95% CI, 81.0-93.0) to 87.0% (95% CI, 81.0-93.0) and 83.2% (95% CI, 0.76-0.90) after manipulation (P<.0001), without affecting specificity (P=.45). Subjects correctly identified 41 previously incorrectly identified esophageal intubations. Paramedic experience, previous intubations, and POCUS experience did not correlate with ability to identify tube location.
Paramedics can accurately identify esophageal intubations with POCUS, and manipulation improves identification. Further studies of paramedic use of dynamic POCUS to identify inadvertent esophageal intubations are needed.
LemaPC, O’BrienM, WilsonJ, St. JamesE, LindstromH, DeAngelisJ, CaldwellJ, MayP, ClemencyB.Avoid the Goose! Paramedic Identification of Esophageal Intubation by Ultrasound. Prehosp Disaster Med.2018;33(4):406–410
We compared sepsis “time zero” and Centers for Medicare and Medicaid Services (CMS) SEP-1 pass rates among 3 abstractors in 3 hospitals. Abstractors agreed on time zero in 29 of 80 (36%) cases. Perceived pass rates ranged from 9 of 80 cases (11%) to 19 of 80 cases (23%). Variability in time zero and perceived pass rates limits the utility of SEP-1 for measuring quality.
Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.
The insurance hypothesis is a reasonable explanation for the current obesity epidemic. One alternative explanation is that the marketing of high-sugar foods, especially sugar-sweetened beverages, drives the rise in obesity. Another prominent hypothesis is that obesity spreads through social influence. We offer a framework for estimating the extent to which these different models explain the rise in obesity.
Alterations in the visual system may underlie visual hallucinations in
dementia with Lewy bodies (DLB). However, cortical excitability as measured
by transcranial magnetic stimulation (TMS) and functional magnetic resonance
imaging (fMRI) activation of lower visual areas (V1–3) to visual stimuli
appear normal in DLB. We explored the relationship between TMS-determined
phosphene threshold and fMRI-related visual activation and found a positive
relationship between the two in controls but a negative one in DLB. This
double dissociation suggests a loss of inhibition in the visual system in
DLB, which may predispose individuals to visual dysfunction and visual
Imaging biomarkers for Alzheimer's disease include medial temporal lobe
atrophy (MTLA) depicted on computed tomography (CT) or magnetic resonance
imaging (MRI) and patterns of reduced metabolism on fluorodeoxyglucose
positron emission tomography (FDG-PET).
To investigate whether MTLA on head CT predicts the diagnostic usefulness
of an additional FDG-PET scan.
Participants had a clinical diagnosis of Alzheimer's disease
(n = 37) or dementia with Lewy bodies (DLB;
n = 30) or were similarly aged controls
(n = 30). We visually rated MTLA on coronally
reconstructed CT scans and, separately and blind to CT ratings, abnormal
appearances on FDG-PET scans.
Using a pre-defined cut-off of MTLA ⩾5 on the Scheltens (0–8) scale, 0/30
controls, 6/30 DLB and 23/30 Alzheimer's disease had marked MTLA. FDG-PET
performed well for diagnosing Alzheimer's disease v. DLB
in the low-MTLA group (sensitivity/specificity of 71%/79%), but in the
high-MTLA group diagnostic performance of FDG-PET was not better than
In the presence of a high degree of MTLA, the most likely diagnosis is
Alzheimer's disease, and an FDG-PET scan will probably not provide
significant diagnostic information. However, in cases without MTLA, if
the diagnosis is unclear, an FDG-PET scan may provide additional
clinically useful diagnostic information.