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Cardiovascular co-morbidities, inflammation and cerebral small vessel disease
No full textCerebral small vessel disease (cSVD) is the most common cause of vascular cognitive impairment and affects all levels of the brain’s vasculature. Features include diverse structural and functional changes affecting small arteries and capillaries that lead to a decline in cerebral perfusion. Due to an aging population, incidence of cerebral small vessel disease (cSVD) is continually rising. Despite its prevalence and its ability to cause multiple debilitating illnesses, such as stroke and dementia, there are currently no therapeutic strategies for the treatment of cSVD. In the healthy brain, interactions between neuronal, vascular and inflammatory cells are required for normal functioning. When these interactions are disturbed, chronic pathological inflammation can ensue. The interplay between cSVD and inflammation has attracted much recent interest and this review discusses chronic cardiovascular diseases, particularly hypertension, and explores how the associated inflammation may impact on the structure and function of the small arteries of the brain in cSVD. Molecular approaches in animal studies are linked to clinical outcomes in patients and novel hypotheses regarding inflammation and cSVD are proposed that will hopefully stimulate further discussion and study in this important area
Assessment of the Wolf method using the Stillinger-Lovett sum rules: from strong electrolytes to weakly charged colloidal dispersions
No full textThe Ewald method has been the cornerstone in molecular simulations for modeling electrostatic interactions of charge-stabilized many-body systems. In the late nineties, Wolf and collaborators developed an alternative route to describe the long-range nature of electrostatic interactions; from a computational perspective, this method provides a more efficient and straightforward way to implement long-range electrostatic interactions than the Ewald method. Despite these advantages, the validity of Wolf potential to account for the electrostatic contribution in charged fluids remains controversial. To alleviate this situation, in this contribution, we implement the Wolf summation method to both electrolyte solutions and charged colloids with moderate size and charge asymmetries in order to assess the accuracy and validity of the method. To this end, we verify that the proper selection of parameters within the Wolf method leads to results that are in good agreement with those obtained through the standard Ewald method and the theory of integral equations of simple liquids within the so-called hypernetted chain approximation. Furthermore, we show that the results obtained with the original Wolf method do satisfy the moment conditions described by the Stillinger-Lovett sum rules, which are directly related to the local electroneutrality condition and the electrostatic screening in the Debye-Hückel regime. Hence, the fact that the solution provided by the Wolf method satisfies the first and second moments of Stillinger-Lovett proves, for the first time, the reliability of the method to correctly incorporate the electrostatic contribution in charge-stabilized fluids. This makes the Wolf method a powerful alternative compared to more demanding computational approaches
Descriptive Analysis Of The Context Of Child Sexual Abuse Reportedly Perpetrated By Female Suspects: Insights From Clients Attending Saint Mary’s Sexual Assault Referral Centre 2012-2015
No full textBackgroundDetermining the prevalence and characteristics of female-perpetrated child sexual abuse (CSA) is fraught with difficultly. There is a historical lack of empirical research and a discrepancy between the number of cases that reach the attention of the authorities and its suspected prevalence in society. It is also noted that for a myriad of reasons many CSA reports do not progress through the criminal justice process so many remain as allegations rather than proven or disproven crimes.ObjectivesThe study set out to answer the research questions: ‘What are the characteristics and context of CSA reportedly perpetrated by females, and what are the similarities and differences in the context of alleged CSA committed by male and female suspects?’Participants and setting This study presents data from all service users aged 0-17 years (n=986) that attended Saint Mary’s Sexual Assault Referral Centre (SARC) for a forensic medical examination over a three-year period.MethodsData collection was performed retrospectively from the paper case files recorded at the time of attendance. Due to the small number of female suspects, analysis was restricted to frequency calculations.Results Results show females were reportedly involved in the alleged abuse of less than 4% of the children attending SARC. Females appeared more likely to be associated with the alleged abuse of younger children and abuse occurring within the child’s home. ConclusionsThis study’s most arresting feature is that despite the large number of CSA cases examined, it was rare to have a female suspect. This study demonstrates how much is still unknown about female-perpetrated CSA. <br/
Current perspectives on the benefits, risks and limitations of non-invasive brain stimulation (NIBS) for post-stroke dysphagia
No full textIntroduction: Studies have shown that non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), can promote neuroplasticity, which is considered important for functional recovery of swallowing after stroke. Despite extensive studies on NIBS, there remains a gap between research and clinical practice.Areas covered: In this article, we update the current knowledge on the benefits and challenges of rTMS and tDCS for post-stroke dysphagia. We identify some key limitations of these techniques that hinder the translation from clinical trials to routine practice. Finally, we discuss the future of NIBS as a treatment for post-stroke dysphagia in real-world settings.Expert opinion: Current evidence suggests that rTMS and tDCS show promise as a treatment for post-stroke dysphagia. However, these techniques are limited by the response variability, uncertainty on the safety in patients with comorbidities and difficulties in clinical study designs. Such limitations call for further work to enhance their utility through individualised approaches. Despite this, the last decade has seen a growing acceptance towards these techniques among clinical personnel. As such, we advocate caution but support optimism that NIBS will gradually be recognised as a mainstream treatment approach for post-stroke dysphagia in the future
A systematic review and meta-ethnographic synthesis of Mindfulness-based Cognitive Therapy for people with major depression
No full textBackgroundMBCT is a relapse-prevention intervention for people experiencing major depression. Three qualitative meta-syntheses investigating experiences of taking part in MBCT and/or Mindfulness-based Stress Reduction (MBSR) across different diagnostic populations reported themes including control, choice, group processes, relationships, and struggles. As multiple studies have been published since, we aimed to update, systematically review, and synthesise the experiences of participants with depression taking part in MBCT. MethodsFour databases were searched systematically (PsycInfo, Web of Science, Medline, CINAHL) up to and including the 12th November 2021. Twenty-one qualitative studies met the review criteria. All papers were rated as fair using a quality appraisal tool. Meta-ethnography was applied.ResultsAcross 21 studies of participants with current or previous depression who had participated in MBCT, three overarching themes were developed: “Becoming skilled and taking action”, “Acceptance”, and “Ambivalence and Variability”. Participants became skilled through engagement in mindfulness practices, reporting increased awareness, perspective, and agency over their experiences. Participants developed acceptance towards their experiences, self, and others. There was variability and ambivalence regarding participants’ expectations and difficulties within mindfulness practices. Limitations Many studies were conducted in MBCT-research centres who may hold conflicts of interest. Many studies did not address the impact of the participant-researcher relationship thus potentially affecting their interpretations. Studies were skewed towards the experiences of female participants. ConclusionsOur findings help to enhance participant confidence in MBCT, alongside understanding the processes of change and the potential for difficulties. MBCT is beneficial and provides meaningful change for many but remains challenging for some. <br/
Evaluation of Process Bus Data Latency with PRP/HSR Enabled Ethernet Switches
No full textUnderstanding the switching behaviours of Ethernet switches is critically important for analysing the transfer time of time-critical messages, e.g. Sampled Value (SV) and Generic Object Oriented Substation Event (GOOSE) messages in a complex IEC 61850 Ethernet network. Most analytical models and simulation programs estimate the network latency by assuming a symmetrical port speed at ingress and egress ports with fixed switching delays. However, the switching characteristics are product-specific and can vary significantly depending on the types of switching hardware, transferred messages and port speed. This paper evaluates the switching characteristics of PRP/HSR enabled switches by analysing the time required to forward SV, GOOSE and IEEE 1588 messages using various port types and speeds combinations. The obtained switching behaviours provide an insight into the multi-protocol traffic interactions at substation process bus. The results can also be used as a performance reference for power engineers and academic researchers to improve the accuracy of analytical models and simulation platforms
Lead optimisation of dehydroemetine for repositioned use in malaria
No full textDrug repositioning offers an effective alternative to de novo drug design to tackle the urgent need for novel anti-malarial treatments. The anti-amoebic compound, emetine dihydrochloride, has been identified as a potent in-vitro inhibitor of the multi-drug resistant strain K1 of Plasmodium falciparum (IC50: 47 nM + 2.1 nM). 2,3-dehydroemetine, a synthetic analogue of emetine dihydrochloride has been claimed to have less cardiotoxic effects than emetine. The structures of two diastereoisomers of 2,3-dehydroemetine were modelled on the reported emetine binding site on cryo-EM structure 3J7A and it was found that (-)-R,S-dehydroemetine mimicked the bound pose of emetine more closely than (-)-S,S-dehydroisoemetine. (-)-R,S-dehydroemetine was also found to be highly potent against the multi-drug resistant K1 strain of P. falciparum in comparison with (-)-S,S-dehydroisoemetine, which loses its potency due to the change of configuration at C-1´. In addition to its effect on the asexual erythrocytic stages of P. falciparum, the compounds exhibited gametocidal properties with no cross-resistance against any of the multi-drug resistant strains tested. Drug interaction studies showed (-)-R,S-dehydroemetine to have synergistic antimalarial activity with atovaquone and proguanil. Emetine dihydrochloride, and (-)-R,S-dehydroemetine failed to show any inhibition of the hERG potassium channel and displayed atovoquone-like activity on the mitochondrial membrane potential. <br/
Urbanisation, land use transformation and spatio-environmental impacts: analyses of trends and implications in major metropolitan regions of Ghana
No full textUrbanization induces spatial and environmental changes. Monitoring and understanding the nature of these changes is crucial to achieving sustainable urban development imperatives. To this end, this paper examines the evolution and spatio-environmental impacts of rapid urbanization in two major metropolitan regions of Ghana—Accra-City Region and the Greater Kumasi Sub-Region. The analysis uses Landsat satellite data and landscape metrics to examine land use transitions and to characterize the emergent landscapes over the last three decades. The results show that built-up land has increased significantly in these metropolitan regions largely at the expense of environmental land cover classes. The expansion process follows a general trend where the historical-core zones were initially sites of rapid land cover conversion to built-up, with settlements in the suburban and peripheral zones expanding in recent years and becoming integrated into the conterminous urban areas of the metropolitan regions. The analysis also uncovered a unique, dynamic and complex process whereby the urban-open-space class, being in a permanent state of flux, mediates transitions between built-up land and vegetation and vice versa. The metric-based land use transformation analysis shows that the landscape of the metropolitan regions has fragmented because of an increased expansion and aggregation of patches of built-up land in the core areas and leapfrog, sprawling expansion in the outlying suburban and peripheral zones. The paper concludes on the need for integrative urban growth management strategies that brings together spatial planning and environmental resource governance to avert the negative consequences on the natural environment of unfettered urban expansion
Shared Autonomous Mobility-on-Demand: Learning-based approach and its performance in the presence of traffic congestion
No full textMobility-on-demand systems consisting of shared autonomous vehicles (SAVs) are expected to improve the efficiency of urban mobility through reduced vehicle ownership and parking demand. However, several issues in their implementation remain open, such as unifying the vehicle and ride-sharing assignment with rebalancing non-occupied vehicles. Furthermore, proposed SAV systems are evaluated in isolation from other traffic; no congestion is taken into account when assigning requests or calculating routes. To address this gap, we presentShared Autonomous Mobility-on-Demand system (SAMoD), a reinforcement learning-based approach to vehicle relocation and ride-sharing request assignment. Each vehicle learns its pick-up and rebalancing behaviour based on local current and observed historical demand. We evaluate SAMoD on Manhattan network using NYC taxi data in microsimulator SUMO. We investigate SAMoD performance in the presence of congestion generated by private vehicles, as well as investigate impact of different percentages of SAMoD vehicles in the system on overall traffic network performanc
‘Umbrella’ review of family-focused care interventions supporting families where a family member has a long-term condition
No full textAim: To summarise reviews of family-focused care interventions that support families with a family member with a long-term condition across the life course.Design: Umbrella review.Data sources: Medline (1946- 2019), Cochrane Data Base of Systematic Reviews (2019), Database of Abstracts of Reviews of Effect and EMBASE (1947- 2019), CINAHL (1981-2019), Health Technology Assessment Database (2019) and PsycInfo (1806-2019).Review Methods: All authors independently undertook title/abstract screening, data extraction and quality appraisal on a cluster of papers, working in groups of two or three to reach a consensus. The AMSTAR tool was used to appraise the quality of the studies and descriptive syntheses were undertaken.Results: Fifteen reviews met the selection criteria. Overall family-focussed care and associated terms were poorly defined. Typically interventions were educational or psychological therapy/counselling with the goal of empowering individuals to manage their condition. There is some evidence that family-focused care interventions can improve clinical/biological health measures and self-care outcomes such as treatment adherence. Multi-component psychosocial interventions that include cognitive-behavioral therapy, skills training, education and support and are focused on wider family members appear to improve family relationships and martial functioning.Conclusion: Long-term conditions have an impact on individual and family health and well-being, yet the impact of family-focused care interventions on family outcomes was overall inconclusive. A better understanding of how family-focused care interventions improve the health and well-being of individuals and their families is needed to promote the inclusion of family-focused care into practice.Impact: Supporting people with a long-term condition is a key health and social care priority. Family-focused care interventions have potential to improve the health and well-being of individuals and families but there is a need to evaluate their clinical and cost effectiveness. The findings from this review could be used by funding bodies when commissioning research for long-term conditions