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Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC).
Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC.
Participants were recruited from Memory Services in the North East of England.
Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC.
Olfaction was assessed using SS-16 and a questionnaire.
Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62–3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51–5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69–94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them.
MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.
The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed).
Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer’s disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer’s Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall.
MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p = .03, g = .45; Digit Symbol Substitution Test (DSST): p = .04, g = .47; DSST Error Check: p < .001, g = .68] and executive function [Trail Making Test Ratio (A/B): p = .04, g = .52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p = .01, g = .46) and verbal (Rey Auditory Verbal Learning Test: p = .04, g = .42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps > .05)
MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.
Electroencephalographic (EEG) abnormalities are greater in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) than in MCI due to Alzheimer’s disease (MCI-AD) and may anticipate the onset of dementia. We aimed to assess whether quantitative EEG (qEEG) slowing would predict a higher annual hazard of dementia in MCI across these etiologies. MCI patients (n = 92) and healthy comparators (n = 31) provided qEEG recording and underwent longitudinal clinical and cognitive follow-up. Associations between qEEG slowing, measured by increased theta/alpha ratio, and clinical progression from MCI to dementia were estimated with a multistate transition model to account for death as a competing risk, while controlling for age, cognitive function, and etiology classified by an expert consensus panel.
Over a mean follow-up of 1.5 years (SD = 0.5), 14 cases of incident dementia and 5 deaths were observed. Increased theta/alpha ratio on qEEG was associated with increased annual hazard of dementia (hazard ratio = 1.84, 95% CI: 1.01–3.35). This extends previous findings that MCI-LB features early functional changes, showing that qEEG slowing may anticipate the onset of dementia in prospectively identified MCI.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Along with an increase in opioid deaths, there has been a desire to increase the accessibility of naloxone. However, in the absence of respiratory depression, naloxone is unlikely to be beneficial and may be deleterious if it precipitates withdrawal in individuals with central nervous system (CNS) depression due to non-opioid etiologies.
The aim of this study was to evaluate how effective prehospital providers were in administering naloxone.
This is a retrospective study of naloxone administration in two large urban Emergency Medical Service (EMS) systems. The proportion of patients who had a respiratory rate of at least 12 breaths per minute at the time of naloxone administration by prehospital providers was determined.
During the two-year study period, 2,580 patients who received naloxone by prehospital providers were identified. The median (interquartile range) respiratory rate prior to naloxone administration was 12 (6-16) breaths per minute. Using an a priori respiratory rate of under 12 breaths per minute to define respiratory depression, only 1,232 (47.8%; 95% CI, 50.3%-54.2%) subjects who received naloxone by prehospital providers had respiratory depression.
This study showed that EMS providers in Los Angeles County, California (USA) frequently administered naloxone to individuals without respiratory depression.
Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage – more specifically, inflammatory biomarkers present in baseline serology.
We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor.
Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage).
Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.
We examined the return on investment (ROI) from the Endovascular Reperfusion Alberta (ERA) project, a provincially funded population-wide strategy to improve access to endovascular therapy (EVT), to inform policy regarding sustainability.
We calculated net benefit (NB) as benefit minus cost and ROI as benefit divided by cost. Patients treated with EVT and their controls were identified from the ESCAPE trial. Using the provincial administrative databases, their health services utilization (HSU), including inpatient, outpatient, physician, long-term care services, and prescription drugs, were compared. This benefit was then extrapolated to the number of patients receiving EVT increased in 2018 and 2019 by the ERA implementation. We used three time horizons, including short (90 days), medium (1 year), and long-term (5 years).
EVT was associated with a reduced gross HSU cost for all the three time horizons. Given the total costs of ERA were $2.04 million in 2018 ($11,860/patient) and $3.73 million in 2019 ($17,070/patient), NB per patient in 2018 (2019) was estimated at −$7,313 (−$12,524), $54,592 ($49,381), and $47,070 ($41,859) for short, medium, and long-term time horizons, respectively. Total NB for the province in 2018 (2019) were −$1.26 (−$2.74), $9.40 ($10.78), and $8.11 ($9.14) million; ROI ratios were 0.4 (0.3), 5.6 (3.9) and 5.0 (3.5). Probabilities of ERA being cost saving were 39% (31%), 97% (96%), and 94% (91%), for short, medium, and long-term time horizons, respectively.
The ERA program was cost saving in the medium and long-term time horizons. Results emphasized the importance of considering a broad range of HSU and long-term impact to capture the full ROI.
In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consenus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology, (ACC) and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate follow-up in pediatric patients.
Due to the falling costs of computational resources and the increasing potential of data acquisition, interest in digital twins, a virtual copy of the physical original, and their industrial application is increasing. Nevertheless, there is limited published work on how to support the process of physical to virtual twinning and what its key aspects are. The aim of this study is to present insights with regards to physical to virtual twinning gained from modelling projects in mechatronic product development. We conducted a survey and in-depth interviews with members of modelling projects. In the surveys and interviews we identified how physical products and virtual models were linked, which virtual models were used and which general challenges and key aspects are considered important by the project members. Our findings show that the key characteristics that pose challenges to modelling regarding physical to virtual twinning are model granularity, model validation, and model integration and interconnectivity.
The approach of functional integration has the potential to solve challenges regarding lightweight design and resource efficiency since the number of parts and therefore the weight and needed installation space can be reduced. One important step in developing integrative concepts is the pre-selection of suitable functions or components. Previous methods of pre-selection take various aspects into account. However, pre-selection based on these methods usually requires additional tables and forms, whose preparation and editing quickly becomes time-consuming. At the same time, most of the development engineers are working on CAD models. However, their use in the selection of suitable integration partners is not yet supported sufficiently. The development of more than 80 concepts on five different vehicles has shown that the consideration of geometric properties (position, orientation, size) is effective, as they can be identified with minimal analysis effort while working on CAD. In this paper a four-step procedure is presented how integration partners can be identified directly on the basis of CAD models. A following evaluation with development engineers in practice completes the research.
The protected Tel-Dor coastal embayment in the eastern Mediterranean preserves an unusually complete stratigraphic record that reveals human–environmental interactions throughout the Holocene. Interpretation of new seismic profiles collected from shallow marine geophysical transects across the bay show five seismic units were correlated with stratigraphy and age dates obtained from coastal and shallow-marine sediment cores. This stratigraphic framework permits a detailed reconstruction of the coastal system over the last ca. 77 ka as well as an assessment of environmental factors that influenced some dimensions of past coastal societies. The base of the boreholes records lowstand aeolian deposits overlain by wetland sediments that were subsequently flooded by the mid-Holocene transgression. The earliest human settlements are submerged Pottery Neolithic (8.25–7 ka) structures and tools, found immediately above the wetland deposits landward of a submerged aeolianite ridge at the mouth of the bay. The wetland deposits and Pottery Neolithic settlement remains are buried by coastal sand that records a middle Holocene sea-level rise ca. 7.6–6.5 ka. Stratigraphic and geographic relationships suggest that these coastal communities were displaced by sea-level transgression. These findings demonstrate how robust integration of different data sets can be used to reconstruct the geomorphic evolution of coastal settings as well as provide an important addition to the nature of human–landscape interaction and cultural development.
There have been long-standing concerns about communication and safety on the Bethlem site out-of-hours due to its size, acuity and the number of specialist services; these issues were exacerbated by the COVID-19 pandemic. A Quality Improvement Project was designed to address communication and safety concerns from the on-call team at the Bethlem Royal psychiatric hospital out-of-hours through the introduction of weekend safety huddles.
Daily weekend safety huddles were introduced to improve communication regarding workload, acuity, new admissions, seclusion reviews, deteriorating patients; and to improve team cohesiveness and trainee support out-of-hours.
The QIP team involved the deputy medical director, the associate director for speciality units, consultants, the college tutor, specialty registrars and core psychiatry trainees. Prior to initiating the huddles, the QIP team met to decide which specialties to involve, to agree on an agenda and liaise with other sites regarding existing huddles. Once the huddles began in April 2020, the team met periodically to agree next courses of action and to troubleshoot. The huddles initially involved acute services and eventually included CAMHS, Forensic, Older Adults, Specialist Units, all on-call consultants, the on-call registrar, two core trainees, the psychiatric liaison manager and the duty senior nurse.
Data were gathered throughout the QIP using Likert scale surveys which were sent to all junior doctors on the out-of-hours rota. Paper surveys were used initially but were later replaced with Microsoft Forms to ensure anonymity.
The percentage of respondents who answered “most of the time” or “all of the time” increased across all parameters when comparing data from before and after implementation of the safety huddles.
These results included improvement in: understanding of workload and acuity (9% before vs 69% after), discussion of new admissions on site (4% before vs 90% after), discussion of patients with deteriorating mental health (35% before vs 90% after) and physical health (22% before vs 83% after), understanding of number of patients in seclusion (61% before vs 93% after) and feeling part of a cohesive “on-call” team (17% before vs 86% after). In addition, the results suggested a reduction in frequency of safety concerns on site (83% answered at least “sometimes” before vs 62% after).
The results of the final survey demonstrated a measurable and positive impact on communications between the out-of-hours team, improved team cohesiveness and a reduction in safety concerns. The lessons learnt also influenced decisions made in formatting safety huddles at other trust sites.
The National Hospital for Neurology and Neurosurgery provides various services for patients with Functional Neurological Disorder (FND), including a four-week inpatient rehabilitation programme run by an integrated Multi-Disciplinary Team (MDT) of Occupational Therapists (OT), Physiotherapists (PT), Psychologists and Psychiatrists.
We had observed that patients with FND often have medical and psychiatric comorbidities including affective, dissociative, somatic symptom and pain disorders; pharmacological treatments are commonly used. We hypothesised that a high burden of medication, particularly of those which produce dependence, might limit one's ability to entrain therapeutic strategies and therefore benefit from treatment. We additionally hypothesised that patients who had previously tried individual physical or psychological therapies might gain less than those who were treatment-naïve.
In this service evaluation project, we reviewed records from 97 consecutive elective inpatient admissions, comprising the entire intake for 2019 and 2020. Data were extracted from the inpatient discharge summary and therapies discharge report of each patient. We recorded which therapies for FND patients had previously tried (OT; PT; Speech and Language Therapy; Psychology; Pain Service) and the classes of medications they were taking on admission (opiates; benzodiazepines; antidepressants; mood stabilisers; antipsychotics; gabapentinoids). We compared the differentials in outcome measures recorded on the first and last day, including the Canadian Occupational Performance Measure (n = 79) and EQ-5D-5L (n = 79). Statistical tests of effect size and significance were done using SPSS-25. Group comparisons of EQ-5D-5L were made with Paired t-tests; all other comparisons were done with Wilcoxon signed-rank tests due to non-normal data.
The most common medications used were antidepressants (72%), gabapentinoids (39%), opiates (36%) and benzodiazepines (25%). 69% of patients had tried PT, 57% psychology and 52% OT, while only 13% were treatment naïve. Whole-cohort analysis revealed highly significant improvements (p < 0.001) in occupational performance, satisfaction, ratings of general health, subjective difficulty in performing tasks and in pain and fatigue levels. We found no significant differences in outcome measures that correlated with past therapies or medication use.
Our analysis shows that the great majority of our patients gained meaningful benefits from their admission, both on clinician-rated metrics of occupational performance and patient-rated measures of subjective improvement. That there was no significant relationship with therapies or medications suggests, promisingly, that patients taking various medications and with suboptimal responses to previous therapy can still benefit from our MDT programme. Limitations include correlational design, limited generalisability to the general population, missing data for certain outcome measures and the absence of follow-up data.
The purpose of this chapter is to review some of the factors that influence laboratory and clinical outcomes, broadly under the heading of optimal handling techniques. Two principal environments are encountered – inside and outside the incubator. The chapter will address media buffers, gas atmosphere, timing and setting up culture or holding vessels, protection of medium performance, temperature relative to handling gametes and embryos, lighting, pH, incubation choices, and workflow. The importance of the interplay between these variables cannot be overlooked.