Statistics and society: a study on the burden experienced by caregivers of patients with Alzheimer

The cost of caring for people with Alzheimer-type diseases is enormous. Caregivers experience emotional, physical and financial stress, and their demands are central to decisions on patient institutionalization. We hereby investigate the burden experienced by caregivers of Alzheimer patients in Cyprus. We explore whether burden is related to variables such as patient psychopathology, caregiver gender, income and level of education. Moreover, we examine if there is a significant difference in the level of burden, depression, or reaction to memory and behavior problems when patients live in the community or in institutions and if the level of burden is associated with the use of different coping strategies by caregivers. Various statistical techniques are implemented for the analysis and all the conclusions are discussed. This work was partially funded by the Cyprus Research Promotion Foundation

In Search for Novel and More Effective Psychological Treatments for Chronic Pain: The “Algea” Research Project

The aim of this paper isto present the objectivesand current state of anongoing multilevelcollaborative researchproject for the study ofpain. “Algea”, the painand suffering deity inancient Greek mythology,was the name given tothis project, which aimsto investigate criticalfactors involved in theexperience of pain, andsuffering. Moreover, theproject will examine theeffects of a novelapproach to treatmentbased on Acceptance andCommitment Therapy.This is a collaborativeproject between theUniversity of Cyprus, theUniversity of Crete, andthe Cyprus Institute ofNeurology and Genetics.Algea is the first systematic effort to examine painrelated parameters and evaluate a noveltherapeutic approach aimed at alleviating thesuffering and interference in living experienced byindividuals with one or more chronic painconditions (e.g., rheumatoid arthritis). The specificobjectives of the “Algea” project include:a) understanding the contributing factors involvedin the experience of pain in individuals withchronic pain (CP) conditions, their dyadicinteractions with their partners, and differenceswith individuals suffering from other chronicillnesses not involving pain; b) designing aculturally sensitive intervention based on newempirical findings stemming from third-wave CBTsfor use in clinical settings (i.e., CP organizations,CP rehabilitation and outpatients units, etc.); c)evaluating via randomized clinical trials theacceptability and effectiveness of this interventionespecially in reducing suffering, interference ofpain and medical utilization in various chronic painconditions; d) training interested healthprofessionals in this new approach and widelydisseminating it into clinical settings; and e)translating the intervention into a digitally-basedintervention so as to be more accessible and reacha wider audience of CP sufferers

Exact solution for scalar field collapse

We give an exact spherically symmetric solution for the Einstein-scalar field system. The solution may be interpreted as an inhomogeneous dynamical scalar field cosmology. The spacetime has a timelike conformal Killing vector field and is asymptotically conformally flat. It also has black or white hole-like regions containing trapped surfaces. We describe the properties of the apparent horizon and comment on the relevance of the solution to the recently discovered critical behaviour in scalar field collapse.Comment: 10 pages(Latex) (2 figures available upon request), Alberta-Thy-4-9

Graph Theoretical Characteristics of EEG-Based Functional Brain Networks in Patients With Epilepsy: The Effect of Reference Choice and Volume Conduction

It is well-established that both volume conduction and the choice of recording reference (montage) affect the correlation measures obtained from scalp EEG, both in the time and frequency domains. As a result, a number of correlation measures have been proposed aiming to reduce these effects. In our previous work, we have showed that scalp-EEG based functional brain networks in patients with epilepsy exhibit clear periodic patterns at different time scales and that these patterns are strongly correlated to seizure onset, particularly at shorter time scales (around 3 and 5 h), which has important clinical implications. In the present work, we use the same long-duration clinical scalp EEG data (multiple days) to investigate the extent to which the aforementioned results are affected by the choice of reference choice and correlation measure, by considering several widely used montages as well as correlation metrics that are differentially sensitive to the effects of volume conduction. Specifically, we compare two standard and commonly used linear correlation measures, cross-correlation in the time domain, and coherence in the frequency domain, with measures that account for zero-lag correlations: corrected cross-correlation, imaginary coherence, phase lag index, and weighted phase lag index. We show that the graphs constructed with corrected cross-correlation and WPLI are more stable across different choices of reference. Also, we demonstrate that all the examined correlation measures revealed similar periodic patterns in the obtained graph measures when the bipolar and common reference (Cz) montage were used. This includes circadian-related periodicities (e.g., a clear increase in connectivity during sleep periods as compared to awake periods), as well as periodicities at shorter time scales (around 3 and 5 h). On the other hand, these results were affected to a large degree when the average reference montage was used in combination with standard cross-correlation, coherence, imaginary coherence, and PLI, which is likely due to the low number of electrodes and inadequate electrode coverage of the scalp. Finally, we demonstrate that the correlation between seizure onset and the brain network periodicities is preserved when corrected cross-correlation and WPLI were used for all the examined montages. This suggests that, even in the standard clinical setting of EEG recording in epilepsy where only a limited number of scalp EEG measurements are available, graph-theoretic quantification of periodic patterns using appropriate montage, and correlation measures corrected for volume conduction provides useful insights into seizure onset

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

Illness perceptions of COVID-19 in Europe: Predictors, impacts and temporal evolution

Objective: Illness perceptions (IP) are important predictors of emotional and behavioral responses in many diseases. The current study aims to investigate the COVID-19-related IP throughout Europe. The specific goals are to understand the temporal development, identify predictors (within demographics and contact with COVID-19) and examine the impacts of IP on perceived stress and preventive behaviors. Methods: This was a time-series-cross-section study of 7, 032 participants from 16 European countries using multilevel modeling from April to June 2020. IP were measured with the Brief Illness Perception Questionnaire. Temporal patterns were observed considering the date of participation and the date recoded to account the epidemiological evolution of each country. The outcomes considered were perceived stress and COVID-19 preventive behaviors. Results: There were significant trends, over time, for several IP, suggesting a small decrease in negativity in the perception of COVID-19 in the community. Age, gender, and education level related to some, but not all, IP. Considering the self-regulation model, perceptions consistently predicted general stress and were less consistently related to preventive behaviors. Country showed no effect in the predictive model, suggesting that national differences may have little relevance for IP, in this context. Conclusion: The present study provides a comprehensive picture of COVID-19 IP in Europe in an early stage of the pandemic. The results shed light on the process of IP formation with implications for health-related outcomes and their evolution. © Copyright © 2021 Dias Neto, Nunes da Silva, Roberto, Lubenko, Constantinou, Nicolaou, Lamnisos, Papacostas, Höfer, Presti, Squatrito, Vasiliou, McHugh, Monestès, Baban, Alvarez-Galvez, Paez-Blarrina, Montesinos, Valdivia-Salas, Ori, Lappalainen, Kleszcz, Gloster, Karekla and Kassianos

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Spectrum of Phenotypic, Genetic, and Functional Characteristics in Patients With Epilepsy With KCNC2 Pathogenic Variants

Background and ObjectivesKCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyze the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.MethodsIndividuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic, and functional analysis. Cases were referred through clinical and research collaborations. Selected de novo variants were examined electrophysiologically in Xenopus laevis oocytes.ResultsWe identified novel KCNC2 variants in 18 patients with various forms of epilepsy, including genetic generalized epilepsy (GGE), developmental and epileptic encephalopathy (DEE) including early-onset absence epilepsy, focal epilepsy, and myoclonic-atonic epilepsy. Of the 18 variants, 10 were de novo and 8 were classified as modifying variants. Eight drug-responsive patients became seizure-free using valproic acid as monotherapy or in combination, including severe DEE cases. Functional analysis of 4 variants demonstrated gain of function in 3 severely affected DEE cases and loss of function in 1 case with a milder phenotype (GGE) as the underlying pathomechanisms.DiscussionThese findings implicate KCNC2 as a novel causative gene for epilepsy and emphasize the critical role of KV3.2 in the regulation of brain excitability

Patterns of psychological responses among the public during the early phase of COVID-19: A cross-regional analysis

This study aimed to compare the mediation of psychological flexibility, prosociality and coping in the impacts of illness perceptions toward COVID-19 on mental health among seven regions. Convenience sampled online survey was conducted between April and June 2020 from 9130 citizens in 21 countries. Illness perceptions toward COVID-19, psychological flexibility, prosociality, coping and mental health, socio-demographics, lockdown-related variables and COVID-19 status were assessed. Results showed that psychological flexibility was the only significant mediator in the relationship between illness perceptions toward COVID-19 and mental health across all regions (all ps = 0.001–0.021). Seeking social support was the significant mediator across subgroups (all ps range = <0.001–0.005) except from the Hong Kong sample (p = 0.06) and the North and South American sample (p = 0.53). No mediation was found for problem-solving (except from the Northern European sample, p = 0.009). Prosociality was the significant mediator in the Hong Kong sample (p =0.016) and the Eastern European sample (p = 0.008). These findings indicate that fostering psychological flexibility may help to mitigate the adverse mental impacts of COVID-19 across regions. Roles of seeking social support, problem-solving and prosociality vary across regions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

New methodology for optimizing transit priority at the network level

A new methodology for optimizing transit road space priority at the network level is proposed. Transit vehicles carry large numbers of passengers within congested road space efficiently. This aids justification of transit priority. Almost all studies that have investigated transit priority lanes focus at a link or an arterial road level, and no study has investigated road space allocation for priority from a network perspective. The aim of the proposed approach is to find the optimum combination of exclusive lanes in an existing operational transport network. Mode share is assumed variable, and an assignment is performed for both private and transit traffic. The problem is formulated by using bilevel programming, which minimizes the total travel time. The approach is applied to an example network and the results are discussed. The approach can identify the optimal combination of transit priority lanes and achieve the global optimum of the objective function. Areas for further development are discussed