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Cortical excitability has been proposed as a novel neurophysiological marker of neurodegeneration in Alzheimer’s dementia (AD). However, the link between cortical excitability and structural changes in AD is not well understood.
Objective:
To assess the relationship between cortical excitability and motor cortex thickness in AD.
Methods:
In 62 participants with AD (38 females, mean ± SD age = 74.6 ± 8.0) and 47 healthy control (HC) individuals (26 females, mean ± SD age = 71.0 ± 7.9), transcranial magnetic stimulation resting motor threshold (rMT) was determined, and T1-weighted MRI scans were obtained. Skull-to-cortex distance was obtained manually for each participant using MNI coordinates of the motor cortex (x = −40, y = −20, z = 52).
Results:
The mean skull-to-cortex distances did not differ significantly between participants with AD (22.9 ± 4.3 mm) and HC (21.7 ± 4.3 mm). Participants with AD had lower motor cortex thickness than healthy individuals (t(92) = −4.4, p = <0.001) and lower rMT (i.e., higher excitability) than HC (t(107) = −2.0, p = 0.045). In the combined sample, rMT was correlated positively with motor cortex thickness (r = 0.2, df = 92, p = 0.036); however, this association did not remain significant after controlling for age, sex and diagnosis.
Conclusions:
Patients with AD have decreased cortical thickness in the motor cortex and higher motor cortex excitability. This suggests that cortical excitability may be a marker of neurodegeneration in AD.
It is widely accepted that we ought to avoid taking excessive risks of causing gratuitous suffering. The practical implications of this truism, however, depend on how we understand what counts as an excessive risk. Precautionary frameworks help us decide when a risk exceeds the threshold for action, with the recent Birch et al. (2021) framework for assessing invertebrate sentience being one such example. The Birch et al. framework uses four neurobiological and four behavioural criteria to provide an evidence-based standard that can be used in determining when precautionary action to promote invertebrate welfare may be warranted. Our aim in this discussion paper is to provide a new motivation for the threshold approach that the Birch et al. framework represents while simultaneously identifying some possible revisions to the framework that can reduce false positives without abandoning the framework’s precautionary objectives.
Objectives: Patients with mild cognitive impairment (MCI) employ compensatory cognitive processes to maintain independence in day-to-day functioning as compared to patients with Alzheimer’s dementia (AD). The dorsolateral prefrontal cortex (DLFPC) supports cognitive compensation in normal aging and MCI. Using Paired Associative Stimulation combined with Electroencephalography (PAS-EEG) we have previously shown that patients with AD have impaired DLPFC plasticity compared to healthy control (HC) individuals. The aim of this study is to examine whether DLPFC plasticity in individuals with MCI is preserved compared to those with AD and HC, serving as a potential mechanism underlying cognitive compensation in MCI.
Methods: We analyzed a combined cross-sectional data of 47 AD, 16 MCI, and 40 HC participants from three different studies that assessed their DLPFC plasticity using PAS-EEG. PAS-EEG assesses DLPFC plasticity via the induction of Long Term Potentiation (LTP)-like activity, thereby referred to as PAS-LTP. Using multiple regression, we compared PAS-LTP in MCI to PAS-LTP in AD and HCs, after adjusting for age andgender.
Results: Among the 47 participants with AD (mean [SD] age = 75.3 [7] years), 29 were women and 18 were men; among the 16 participants with MCI (mean [SD] age = 74.8 [6] years), 11 were women and 5 were men; and among the 40 HCs (mean [SD] age = 76.4 [5.1] years), 22 were women and 18 were men. After adjusting for age and gender, there was an impact of diagnostic group on PAS-LTP [F (2,95) = 4.19, p = 0.018, between-group comparison η2 = 0.81]. Post-hoc comparisons showed that participants with MCI had a higher PAS-LTP (mean [SD] = 1.31 [0.49]) than those with AD (mean [SD] = 1.09 [0.28]) (Bonferroni corrected p = 0.042) but not different from PAS-LTP in HCs (mean [SD] = 1.25 [0.33]) (Bonferroni corrected p = 1.0).
Conclusions: Our findings indicate that plasticity is preserved in the DLPFC among individuals with MCI, supporting the hypothesis that DLPFC plasticity contributes to cognitive compensation towards delaying progression to AD. Thus, further enhancement of longer preservation of DLPFC plasticity in individuals with MCI could further delay the onset of AD in this population.
Deviant sexual interest for children (pedophilia, hebephilia) is associated with a higher risk of sexual offending against children (CSA) and consuming child sexual abuse images (CSAI). There is a general shortage of therapeutic programs for individuals who feel sexually attracted to juvenile bodies and are concerned about their sexual behaviour. Efforts to establish regional centres throughout Germany offering preventive support led to the prevention network “Don’t become an offender” (“Kein Täter werden”).
Objectives
To identify dynamic risk factors (DRFs) and evaluate a treatment programme aiming to reduce CSA and CSAI among potential or existing pedosexual offenders (who have not been legally charged). In addition, changes in the course of therapy are examined to provide information about the accessibility and motivation of the target group and its therapeutic responsiveness.
Methods
Participants undergo standardized diagnostic and treatment procedures. Therapy comprises an outpatient psychotherapy program (group therapy) over the course of approx. 48 weekly sessions, optional individual and partner/relative including sessions, as well as additional pharmaceutical treatment. Assessments are carried out through self- and other-reported psychometric test batteries pre-, during and post-treatment up to a 3.5 year follow-up. The test battery includes clinical questionnaires (WHO-5, CTQ-SF), personality questionnaires (ISK-K, NEO-FFI), sexuality questionnaires (EKK-R, KV-M, MSI, HBI-19) and risk assessment procedures (VRAG-R, STATIC-99, VRS:SO). Main outcome measures are self- and externally-reported DRF changes well as offending behaviour characteristics.
Results
By September 20, 2023, N=12 individuals were enrolled in the treatment program. All individuals had a deviant sexual preference (exclusive/non-exclusive pedo-/hebephilia). Nine individuals reported past and/or current use of CSAI. Of these, two individuals reported at least one CSA in the past. Three had no previous use of CSAI or CSA history.
In the first treatment group (N=6), preliminary results show reduction in dynamic risk factors (e.g., Cognitive Bias, Sexual Compulsivity, Impulsivity) after the first 12 weeks of treatment. The evaluation of additional clinical data is pending.
Conclusions
To date, therapy for individuals with pedophilia or hebephilia has been insufficient – particularly when not offending. Ongoing evaluation of the therapy program should provide further insight into responsiveness and therapeutic motivation of this target group. In particular, the impact of therapy on changing dynamic risk factors for CSA and CSAI remains to be examined.
At least 200 billion black soldier fly (Hermetia illucens) larvae (BSFL) are reared each year as food and feed, and the insect farming industry is projected to grow rapidly. Despite interest by consumers, producers, and legislators, no empirical evidence exists to guide producers in practicing humane – or instantaneous – slaughter for these novel mini-livestock. BSFL may be slaughtered via freezing, boiling, grinding, or other methods; however standard operating procedures (SOPs) and equipment design may affect the likelihood of instantaneous death using these methods. We tested how larval body size and particle size plate hole diameter affect the likelihood of instantaneous death for black soldier fly larvae that are slaughtered using a standard meat grinder. Larval body size did not affect the likelihood of instantaneous death for larvae that are 106–175 mg in mass. However, particle size plate hole diameter had a significant effect on the likelihood of instantaneous death, with only 54% of larvae experiencing an instant death when using the largest particle size plate (12-mm hole diameter) compared to 84% using the smallest particle size plate (2.55 mm). However, a higher percentage of instantaneous death (up to 99%) could be achieved by reducing the proportion of larvae that become stuck in the machine. We conclude by outlining specific recommendations to support producers in achieving a 99% instantaneous death rate through specific SOPs to be used with similarly designed machines. We also develop a protocol for producers that wish to test their own grinding SOPs.
Common data elements (CDEs) for concussion, as established by international bodies, are not being widely used in Ontario, resulting in significant variability in the data being assessed and collected across clinics. CDEs support standardization of care as well as large-scale data sharing for high impact research. A collaborative network – Concussion Ontario Network: Neuroinformatics to Enhance Clinical care and Translation (CONNECT) – comprised of health care professionals, researchers, members from advocacy groups, and patients was formed to establish and implement CDEs for concussion care and research. While the seeds have been planted and initial effectiveness demonstrated, future challenges exist.
Our limited knowledge of the climate prevailing over Europe during former glaciations is the main obstacle to reconstruct the past evolution of the ice coverage over the Alps by numerical modelling. To address this challenge, we perform a two-step modelling approach: First, a regional climate model is used to downscale the time slice simulations of a global earth system model in high resolution, leading to climate snapshots during the Last Glacial Maximum (LGM) and the Marine Isotope Stage 4 (MIS4). Second, we combine these snapshots and a climate signal proxy to build a transient climate over the last glacial period and force the Parallel Ice Sheet Model to simulate the dynamical evolution of glaciers in the Alps. The results show that the extent of modelled glaciers during the LGM agrees with several independent key geological imprints, including moraine-based maximal reconstructed glacial extents, known ice transfluences and trajectories of erratic boulders of known origin and deposition. Our results highlight the benefit of multiphysical coupled climate and glacier transient modelling over simpler approaches to help reconstruct paleo glacier fluctuations in agreement with traces they have left on the landscape.
Neuropsychiatric symptoms (NPS) are common during the course of neurocognitive disorders. NPS have been previously reported in early and late stages of Alzheimer’s Disease. However, our understanding of NPS in high-risk states for dementia such as mild cognitive impairment (MCI) and major depressive disorder (MDD) is poor.
Objectives
To compare the frequency and factor structure of neuropsychiatric symptoms among individuals with Mild Cognitive Impairment (MCI), Major Depressive Disorder (MDD) in remission, and comorbid MCI and MDD (in remission) (MCI-D).
Methods
We used baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study, a multicenter trial across five academic sites in Toronto, Canada (clinical trial No. NCT0238667). We used ANOVA or χ2-test to compare frequency of NPS across groups. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items in the three groups.
Results
We included 374 participants with a mean age of 72.0 years (SD = 6.3). In the overall sample, at least one NPS was present in 64.2% participants, and 36.1 % had at least moderate severity NPS (36.1%). Depression (54%, χ2 < 0.001) and apathy (28.7%, χ2=0.002) were more prevalent in the MCI-D group as compared to MCI and MDD groups. In factor analysis, NPS grouped differently in MCI, MDD, and MCI-D groups. A “psychotic” subgroup emerged among MCI and MCI-D, but not in MDD. Night-time behaviors and disinhibition grouped differently across all three groups.
Conclusions
Prevalence of NPS seems higher in persons with MCI-D as compared to those with only MCI or MDD. The factor structure of NPS differed between MCI, MDD, and MCI-D groups. Future studies should investigate the association of NPS factors with cognition, function, and illness biomarkers.
Trends in 2-1-1 calls reflect evolving community needs during public health emergencies (PHEs). The study examined how changes in 2-1-1 call volume after 2 PHEs (Hurricane Irma and the coronavirus disease 2019 [COVID-19] pandemic declaration) in Broward County, Florida, varied by PHE type and whether variations differed by gender and over time. Examining 2-1-1 calls during June to December 2016, June to December 2017, and March 2019 to April 2021, this study measured changes in call volume post-PHEs using interrupted time series analysis. Hurricane Irma and the COVID-19 pandemic were associated with increases in call volume (+81 calls/d and +84 calls/d, respectively). Stratified by gender, these PHEs were associated with larger absolute increases for women (+66 and +57 calls/d vs +15 and +27 calls/d for men) but larger percent increases above their baseline for men (+143% and +174% vs +119% and +138% for women). Calls by women remained elevated longer after Hurricane Irma (5 wk vs 1 wk), but the opposite pattern was observed after the pandemic declaration (8 vs 21 wk). PHEs reduce gender differences in help-seeking around health-related social needs. Findings demonstrate the utility of 2-1-1 call data for monitoring and responding to evolving community needs in the PHE context.
This study aimed to: (1) explore changes in the volume of calls to poison control centers (PCs) for intentional exposures (IEs) in Dallas County, Texas, overall and by gender and age, and (2) examine the association between 2 different public health emergencies (PHEs) and changes in IE call volume.
Methods:
PCs categorize calls they receive by intentionality of the exposure, based on information from the caller. We analyzed data on PC calls categorized as intentional in Dallas County, Texas, from March 2019 – April 2021. This period includes the COVID-19 pandemic declaration (March 2020), a surge in COVID-19 cases (July 2020), and Winter Storm Uri (February 2021). Changes in IE call volume (overall and by age and gender), were explored, and interrupted time series analysis was used to examine call volume changes after PHE onset.
Results:
The summer surge in COVID-19 cases was associated with 1.9 additional IE calls/day (95% CI 0.7 to 3.1), in the context of a baseline unadjusted mean of 6.2 calls per day (unadjusted) before November 3, 2020. Neither the pandemic declaration nor Winter Storm Uri was significantly associated with changes in call volume. Women, on average, made 1.2 more calls per day compared to men during the study period. IE calls for youth increased after the pandemic declaration, closing the longstanding gap between adults and youth by early 2021.
Conclusions:
Changes in IE call volume in Dallas County varied by gender and age. Calls increased during the local COVID-19 surge. Population-level behavioral health may be associated with local crisis severity.
Cages for laboratory and pet hamsters are usually small. Using video recordings, the behaviour of sixty female golden hamsters (Mesocricetus auratus), housed individually in four different cage sizes, was compared in order to draw conclusions about their welfare. The cage sizes were 1,800 cm2, 2,500 cm2, 5,000 cm2, and 10,000 cm2. Enrichment items and litter depth were standardised and all cages were equipped with a running-wheel (30 cm diameter). Stereotypic wire-gnawing, usage of the provided space, weight gain, and reactions to mild husbandry stressors were used as welfare indicators. Stereotypic wire-gnawing was observed in all cage sizes, but hamsters in small cages gnawed significantly longer and more frequently. There were no significant differences in running-wheel activity. In small cages hamsters made use of the roof of their wooden shelters as an additional platform more often than in big cages, which could suggest that they needed more space. Therefore, the welfare of pet golden hamsters in cages with a minimal ground floor area of 10,000 cm2 seemed to be enhanced compared with smaller cages.
Societal concern for animals under human care has influenced our approaches to advance animal welfare in a variety of contexts. The Animal Programs Department at the Columbus Zoo and Aquarium sought partnership with the Center for Human-Animal Interactions Research & Education (CHAIRE) at The Ohio State University to develop a holistic welfare approach for the animals within their department using a focal species, the cheetah (Acinonyx jubatus). A one-year project using the Five Domains Animal Welfare Model collected data over six 60-day periods to evaluate long-term cortisol production and behavioural observations of cheetahs under changing environmental factors. Species and individual histories were incorporated with behavioural observations and hair cortisol production, giving a holistic view of welfare. Cortisol and behavioural data were analysed using linear models to compare cheetahs at population and individual levels. Participation in a cheetah run activity, housing occupancy, and 60-day period were found to influence all behaviours within the population and stereotypic behaviour also differed within individual cheetahs. No differences in hair cortisol concentrations were found for the group, but further analysis revealed differences within individuals throughout the study. No correlation of stereotypic behaviour and cortisol levels were found. This study created a welfare assessment protocol that can be used within zoological institutes and was the first to measure cortisol concentrations in hair in cheetahs.
Mental health and psychosocial support (MHPSS) staff in humanitarian settings have limited access to clinical supervision and are at high risk of experiencing burnout. We previously piloted an online, peer-supervision program for MHPSS professionals working with displaced Rohingya (Bangladesh) and Syrian (Turkey and Northwest Syria) communities. Pilot evaluations demonstrated that online, peer-supervision is feasible, low-cost, and acceptable to MHPSS practitioners in humanitarian settings.
Objectives
This project will determine the impact of online supervision on i) the wellbeing and burnout levels of local MHPSS practitioners, and ii) practitioner technical skills to improve beneficiary perceived service satisfaction, acceptability, and appropriateness.
Methods
MHPSS practitioners in two contexts (Bangladesh and Turkey/Northwest Syria) will participate in 90-minute group-based online supervision, fortnightly for six months. Sessions will be run on zoom and will be co-facilitated by MHPSS practitioners and in-country research assistants. A quasi-experimental multiple-baseline design will enable a quantitative comparison of practitioner and beneficiary outcomes between control periods (12-months) and the intervention. Outcomes to be assessed include the Kessler-6, Harvard Trauma Questionnaire and Copenhagen Burnout Inventory and Client Satisfaction Questionnaire-8.
Results
A total of 80 MHPSS practitioners will complete 24 monthly online assessments from May 2022. Concurrently, 1920 people receiving MHPSS services will be randomly selected for post-session interviews (24 per practitioner).
Conclusions
This study will determine the impact of an online, peer-supervision program for MHPSS practitioners in humanitarian settings. Results from the baseline assessments, pilot evaluation, and theory of change model will be presented.
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
Direct numerical simulations of oscillatory boundary-layer flows in the transitional regime were performed to explain discrepancies in the literature regarding the phase difference ${\rm \Delta} \phi$ between the bed-shear stress and free-stream velocity maxima. Recent experimental observations in smooth bed oscillatory boundary-layer (OBL) flows, showed a significant change in the widely used ${\rm \Delta} \phi$ diagram (Mier et al., J. Fluid Mech., vol. 922, 2021, A29). However, the limitations of the point-wise measurement technique did not allow us to associate this finding with the turbulent kinetic energy budget and to detect the approach to a ‘near-equilibrium’ condition, defined in a narrow sense herein. Direct numerical simulation results suggest that a phase lag occurs as the result of a delayed and incomplete transition of OBL flows to a stage that mimics the fully turbulent regime. Data from the literature were also used to support the presence of the phase lag and propose a new ${\rm \Delta} \phi$ diagram. Simulations performed for ${\textit {Re}}_{\delta }=671$ confirmed the sensitivity in the development of self-sustained turbulence on the background disturbances ($\textit{Re}_{\delta}=U_{o}\delta/\nu$, where $\delta=[2\nu/\omega]^{1/2}$ is the Stokes' length, $U_{o}$ is the maximum free stream velocity of the oscillation, $\nu$ is the kinematic viscosity and $\omega=2{\rm \pi}/T$ is the angular velocity based on the period of the oscillation T). Variations of the mean velocity slope and intersect values for oscillatory flows are also explained in terms of the proximity to near-equilibrium conditions. Relaminarization and transition effects can significantly delay the development of OBL flows, resulting in an incomplete transition. The shape and defect factors are examined as diagnostic parameters for conditions that allow the formation of a logarithmic profile with the universal von Kármán constant and intersect. These findings are of relevance for environmental fluid mechanics and coastal morphodynamics/engineering applications.
To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.
Design:
Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed.
Setting:
Community-based multi-centered study based in Toronto across 5 academic sites.
Participants:
Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls.
Measurements:
We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores.
Results:
A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD.
Conclusions:
This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.
Rabies post-exposure prophylaxis (R-PEP) including wound treatment, vaccination and application of rabies immunoglobulin (RIG) is essential in preventing rabies mortality. Today, Germany is officially declared free from terrestrial rabies and rabies is only found in bats. However, physicians in A&E Departments are frequently consulted on the need for R-PEP. We retrospectively analysed patients who received R-PEP at the A&E Department of the University Hospital Bonn between 01.01.2013 and 30.06.2019. Demographic data, travel history, clinical and laboratory findings, previous rabies vaccinations and R-PEP vaccination regimen were recorded. During the study period, 90 patients received R-PEP at the University Hospital Bonn, in 10 cases without indication for R-PEP. Altogether, we found deviations from R-PEP guidelines in 51% (n = 41/80). Infiltration of RIG was missed in 12 patients and incorrectly administrated in 24 patients. Furthermore, vaccination scheme was incorrect in 11 patients. Correct wound washing and documentation of tetanus status was missing in 14% and 63% of patients, respectively. Despite rabies elimination in Germany patients frequently seek advice for R-PEP, the majority returning from foreign travel. Our data show that there is a high need for education on indication for R-PEP before and after travel and for implementation of precise R-PEP guidelines in daily clinical practice.
Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation.
Objectives:
To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD).
Methods:
Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG.
Results:
There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling.
Conclusions:
This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)