Search

The current legal test for capacity under the common law is a functional test. It determines whether a person can make a particular decision at a particular time; it focuses on retained abilities rather than on presumed deficits - in order to promote patient autonomy in decision-making. International evidence suggests however that the test is not well understood and consequently not being correctly applied in practice by a range of medical professionals. Donnelly has argued that gaining a better understanding of how capacity assessments are actually employed is essential to improving the quality of assessments. To date, there is little data on how doctors in particular make their assessments in practice. Using a socio-legal methodology, this quantitative study aims to assess understanding of capacity among a group of general practitioners/family medicine doctors in Ireland, and to determine how they assess capacity in clinical practice. Our study found that notwithstanding a lack of confidence in their ability to assess decision-making capacity, that respondents in fact demonstrated a high level of understanding and of ability to correctly apply the functional test in practice.

Objectives: Medico-legal and regulatory culture has a significant impact on medical practitioners, including the decision of graduates to enter high-risk specialties. This study explores the impact of the current medico-legal and regulatory culture in Ireland on the decision of graduate entry medical students to enter one high risk specialty, obstetrics and gynecology., Study Design: We conducted a survey of 146 final-year, graduate-entry medical students pre- and post- a 6-week rotation in obstetrics and gynecology in Ireland. Participants were asked to rate the influence (on a four-point scale) of factors such as fear of being sued, being reported to the regulatory body or criminal prosecution on their decision to pursue a career in obstetrics or gynaecology. Data were matched pre- and post-rotation and McNemar-Bowker's test was used to test for differences in related data. All analysis was conducted using SPSS for Windows version 25., Results: The responses of 72 students to both questionnaires could be matched (response rate 49.3%). The majority of participants pre-rotation reported that fear of being sued (74%), fear of being reported to the regulatory body (70%) and fear of criminal prosecution (55%) were factors influencing their decision (somewhat or to a great extent) to pursue a career in obstetrics. There were no significant changes post-rotation. Compared to obstetrics, lower proportions of participants pre-rotation considered fear of being sued (54%), fear of being reported to the regulatory body (50%) and fear of criminal prosecution (40%) as factors influencing their decision to pursue a career in gynecology. There were no significant changes post-rotation., Conclusions: Medico-legal and regulatory culture is shaping the perceptions of graduate entry medical students of obstetrics and gynecology and influencing their decision to pursue a career in the speciality. Understanding the impact of medico-legal culture on career choices including a high-risk specialty such as obstetrics and gynecology is important from both a policy and reform context, and if the healthcare service is to recruit and retain adequate numbers to ensure the safe provision of healthcare., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

To achieve insights in antiviral immune defense of the central nervous system (CNS), we investigated T cells and CD45 cells in the marine fish model Dicentrarchus labrax infected with the CNS-tropic virus betanodavirus. By employing markers for pan-T cells (mAb DLT15) and CD45-cells (mAb DLT22) in immunofluorescence (IIF) of leukocytes from brain, we obtained 3,7 ± 2.3 % of T cells and 7.3 ± 3.2 % of CD45 + cells. Both IIF and immunoelectron microscopy confirmed a leukocyte/glial morphology for the immunoreactive cells. Quantitative immunohistochemistry (qIHC) of brain/eye sections showed 1.9 ± 0.8 % of T + cells and 2 ± 0.9 % of CD45 + cells in the brain, and 3.6 ± 1.9 % and 4.1 ± 2.2 % in the eye, respectively. After in vivo RGNNV infection the number of T cells/CD45 + leukocytes in the brain increased to 8.3 ± 2.1 % and 11.6 ± 4.4 % (by IIF), and 26.1 ± 3.4 % and 45.6 ± 5.9 % (by qIHC), respectively. In the eye we counted after infection 8.5 ± 4.4 % of T cells and 10.2 ± 5.8 % of CD45 cells. Gene transcription analysis of brain mRNA revealed a strong increase of gene transcripts coding for: antiviral proteins Mx and ISG-12; T-cell related CD3ε/δ, TcRβ, CD4, CD8α, CD45; and for immuno-modulatory cytokines TNFα, IL-2, IL-10. A RAG-1 gene product was also present and upregulated, suggesting somatic recombination in the fish brain. Similar transcription data were obtained in the eye, albeit with differences. Our findings provide first evidence for a recruitment and involvement of T cells and CD45 + leukocytes in the fish eye-brain axis during antiviral responses and suggest similarities in the CNS immune defense across evolutionary distant vertebrates., Competing Interests: Declaration of competing interest Authors declare there are no competing financial interests in relation to the work described., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Challenges in recruiting appropriately trained obstetricians and gynaecologists have been identified across the world. Given well documented staff shortages within obstetrics and gynaecology in Ireland, it is increasingly important to understand the factors which influence medical students to choose or reject a career in the speciality. The aim of this study was to ascertain the perceptions of final year graduate entry medical students of obstetrics and gynaecology, including the factors which may influence a student's decision to pursue in a career in the speciality., Methods: Paper-based surveys of graduate entry medical students (n = 146) were conducted at the beginning and end of a six week rotation in obstetrics and gynaecology in Ireland. Responses to the surveys pre- and post-rotation were matched and changes in career choices, merits and demerits over time were analysed. All analysis was conducted using SPSS for Windows version 25., Results: The responses of 72 students to both questionnaires could be matched (response rate of 49.3%). No male students expressed an interest in obstetrics, gynaecology or both as a first choice of career in the pre rotation survey. Obstetrics as a first choice of career increased from 6.9% pre rotation to 19.4% post rotation (p = 0.04) and this increase was seen in male and female students. Gynaecology as a first choice increased slightly from 1.4 to 4.2% (p = 0.50) and the dual speciality increased from 6.9 to 13.9% (p = 0.23). Students identified many merits of obstetrics pre-rotation with more than 60% identifying it as exciting, interesting fulfilling and challenging. However, incompatibility with family life was cited as a demerit by 72% of respondents and 68.1% identified fear of litigation as a demerit. Participants were less positive overall about the merits of a career in gynaecology with less than 40% viewing it as exciting, fulfilling, and varied., Conclusions: While respondents were positive about the merits of a career in obstetrics and gynecology, concerns remain about work-life balance, career opportunities, and the high-risk nature of the specialty. These concerns should be addressed by the profession and policy makers if they wish to attract sufficient numbers to address anticipated need in the coming years. Gender differences in speciality choice were also evident. If males are to be recruited into obstetrics and gynaecology, consideration should be given to the positive impact of internship., (© 2023. The Author(s).)

Background: Previous literature showed significant health disparities between Native American population and other populations such as Non-Hispanic White. Most existing studies for Native American Health were based on non-probability samples which suffer with selection bias. In this paper, we are the first to evaluate the effectiveness of data integration methods, including calibration and sequential mass imputation, to improve the representativeness of the Tribal Behavioral Risk Factor Surveillance System (TBRFSS) in terms of reducing the biases of the raw estimates., Methods: We evaluated the benefits of our proposed data integration methods, including calibration and sequential mass imputation, by using the 2019 TBRFSS and the 2018 and 2019 Behavioral Risk Factor Surveillance System (BRFSS). We combined the data from the 2018 and 2019 BRFSS by composite weighting. Demographic variables and general health variables were used as predictors for data integration. The following health-related variables were used for evaluation in terms of biases: Smoking status, Arthritis status, Cardiovascular Disease status, Chronic Obstructive Pulmonary Disease status, Asthma status, Cancer status, Stroke status, Diabetes status, and Health Coverage status., Results: For most health-related variables, data integration methods showed smaller biases compared with unadjusted TBRFSS estimates. After calibration, the demographic and general health variables benchmarked with those for the BRFSS., Conclusion: Data integration procedures, including calibration and sequential mass imputation methods, hold promise for improving the representativeness of the TBRFSS., (© 2023. The Author(s).)

Coercive measures to protect public health are controversial, eliciting questions regarding state-patient relationships and conflicts between individual autonomy and public good. This is challenging in a time when respect for patient autonomy has become elevated yet society faces an increasing number of public health challenges, the most recent being the SARS-CoV-2 virus (COVID-19). In that context, there is emphasis on increasing vaccination rates internationally in order to achieve "herd immunity", raising the possibility of compulsory vaccination of populations in the future. Here, we explore current rights of individuals to decline vaccination, utilising prior learning from other viral pathogens internationally (specifically, measles, mumps and rubella), and related public health outcomes. Further, we consider freedom of choice versus mandatory treatment necessitated to avoid contagion during disease outbreaks (such as COVID-19). In doing so, we utilise rhetorical reasoning in the form of casuistry focusing on the core challenges regarding public good versus personal antipathy towards vaccination., (© 2022. The Author(s).)

Introduction: It has been reported internationally that doctors have a limited understanding of the legal standard that applies to decision making capacity (DMC). No research on this has been conducted in Ireland to date. We sought to assess the understanding of legal principles relating to capacity and consent among Irish general practitioners (GPs), alongside how DMC assessments are conducted., Methods: This study utilised a cross-sectional cohort model circulating online questionnaires to Irish GPs associated with a university research network. Data were analysed using SPSS to conduct a variety of statistical tests., Results: There were 64 participants, with 50% aged 35-44 years and 60.9% being female. Of these, 62.5% found DMC assessments time-consuming. Only 10.9% of participants felt extremely confident in their abilities; most participants (59.4%) felt 'somewhat confident' in their ability to assess DMC. Also, 90.6% of GPs routinely engaged with families when assessing capacity. GPs felt their medical training did not prepare them for DMC assessment (undergraduate 90.6%, non-consultant hospital doctor 78.1%, GP training 65.6%). 70.3% felt guidelines relating to DMC would be helpful and 65.6% felt they needed additional training., Discussion and Conclusions: Most GPs recognise the importance of DMC assessment, and it is not considered a complex or burdensome task. There was limited knowledge of the legal instruments relevant to DMC. GPs felt there should be extra support available to assist them with DMC assessment; specific guidelines for different categories of patients was found to be the most popular resource requested.

Olive (Olea europaea) is a native species from the Mediterranean region and widely cultivated for its edible fruit, known as olives. Olives are a rich source of monounsaturated fatty acids, vitamin E, and polyphenols, and have been shown to have various health benefits. They are commonly used for cooking and are also employed in cosmetics and the pharmaceutical industry. The extract obtained from olive fruits and several subproducts of the olive industry has demonstrated several biological activities mainly associated with their antioxidant and inflammatory properties. Thus, olives, olive-derived products, and subproducts of the olive industry have gained popularity in recent years due to their potential health benefits and their use in traditional medicine. The present chapter summarizes the main applications of Olea europaea and olive oil processing by-products as therapeutic agents against cancer, cardiovascular diseases, and antimicrobial agents., (Copyright © 2023. Published by Elsevier Inc.)

Abstract: The ocean economy is experiencing rapid growth that will provide benefits but will also pose environmental and social risks. With limited space and degraded resources in coastal areas, offshore waters will be a particular focus of Blue Economy expansion over the next decade. When emerging and established economic sectors expand in offshore waters (within national Exclusive Economic Zones), different potential Blue Economy opportunities and challenges will arise. Following a series of interdisciplinary workshops, we imagine two technically possible futures for the offshore Blue Economy and we identify the actions required to achieve the more sustainable outcome. Under a business as usual scenario the focus will remain on economic growth, the commodification of nature, the dominance of private over public and cultural interests, and prioritisation of the interests of current over future generations. A more sustainable scenario would meet multiple UN Sustainable Development Goals and ensure inclusive economic developments, environmental sustainability, and fair and equitable access to resources and technologies across users, nations, and generations. Challenges to this more sustainable future are a lack of infrastructure and technology to support emerging offshore sectors, limited understanding of environmental impacts, inequitable outcomes, and a lack of planning and governmental oversight. Addressing these challenges will require a shift in societal values, a more balanced allocation of funding to offshore activities, transparency in information sharing between industries and across nations, and adjustment of international legal and institutional mechanisms. The sustainable and equitable offshore Blue Economy we envisage is achievable and provides a unique opportunity to build global capacity and partnership., (© Crown 2021.)

Ocean governance is complex and influenced by multiple drivers and actors with different worldviews and goals. While governance encompasses many elements, in this paper we focus on the processes that operate within and between states, civil society and local communities, and the market, including industry. Specifically, in this paper, we address the question of how to move towards more sustainable ocean governance aligning with the sustainable development goals (SDGs) and the UN Ocean Decade. We address three major risks to oceans that arise from governance-related issues: (1) the impacts of the overexploitation of marine resources; (2) inequitable distribution of access to and benefits from marine ecosystem services, and (3) inadequate or inappropriate adaptation to changing ocean conditions. The SDGs have been used as an underlying framework to develop these risks. We identify five drivers that may determine how ocean governance evolves, namely formal rules and institutions, evidence and knowledge-based decision-making, legitimacy of decision-making institutions, stakeholder engagement and participation, and empowering communities. These drivers were used to define two alternative futures by 2030: (a) 'Business as Usual'-a continuation of current trajectories and (b) 'More Sustainable Future'-optimistic, transformational, but technically achievable. We then identify what actions, as structured processes, can reduce the three major governance-related risks and lead to the More Sustainable Future. These actions relate to the process of co-creation and implementation of improved, comprehensive, and integrated management plans, enhancement of decision-making processes, and better anticipation and consideration of ambiguity and uncertainty., Supplementary Information: The online version of this article (10.1007/s11160-020-09631-x) contains supplementary material, which is available to authorized users., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021.)

Defensive medicine describes behaviours engaged in by physicians, for the purposes of averting the threat of medical negligence litigation and/or complaints. Defensive practice typically encompasses 'assurance' or 'avoidance' behaviours, or 'positive' or 'negative' defensive medicine. Assurance behaviours include, for example, meticulous notetaking and ordering further clinically unnecessary tests, whereas avoidance behaviours encompass actions such as refusing to engage with a patient perceived to be high-risk. Whilst such practices may be understandable, defensive medicine is problematic for a number of reasons: it may result in a lower standard of patient care, where for example, a patient is exposed to unnecessary risk(s); and it can increase healthcare costs, which in turn limits resources. Drawing on the findings of a survey of surgeons in Ireland, this study investigates the existence of defensive practices, and explores the impact of the civil and regulatory responses to patient safety incidents on surgical practice. Given the increasing emphasis on patient safety and cultivating a "no-blame" culture both nationally and internationally, the findings of this research illustrate the tension between the current medico-legal and regulatory environment and medical practice, with implications for quality and safety.

Objective: The objective of this study is to explore the experiences and perspectives of general practitioners' and medical students' use of, and behaviour on, social media and to understand how they negotiate threats to professional and personal life on social media., Design: A two-phase qualitative design was used, consisting of semistructured interviews and follow-up vignettes, where participants were asked to respond to vignettes that involved varying degrees of unprofessional behaviour. Data were analysed using template analysis., Setting and Participants: Participants were general practitioner tutors and third year medical students who had just completed placement on the University of Limerick longitudinal integrated clerkship. Five students and three general practitioners affiliated with the medical school were invited to participate in one-to-one interviews., Results: Three overarching themes, each containing subthemes were reported. 'Staying in contact and up to date' outlines how social media platforms provide useful resources and illustrates the potential risks of social media. 'Online persona' considers how social media has contributed to changing the nature of interpersonal relationships. 'Towards standards and safety' raises the matter of how to protect patients, doctors and the medical profession., Conclusion: Guidance is required for students and medical practitioners on how to establish reasonable boundaries between their personal and professional presence on social media and in their private life so that poorly judged use of social media does not negatively affect career prospects and professional efficacy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Elevated levels of transfer RNA (tRNA) fragments were recently identified in plasma samples from people with epilepsy in advance of a seizure, indicting a potential novel class of circulating biomarker. Current methods for detection and quantitation of tRNA fragments (tRFs) include northern blotting, RNA sequencing or custom Taqman-based PCR assays. The development of a simple, at home or clinic-based test, would benefit from a simple and reliable method to detect the tRFs using small volumes of biofluids. Here we describe an electrochemical direct detection method based on electrocatalytic platinum nanoparticles to detect 3 specific tRFs: 5'AlaTGC, 5'GlyGCC, and 5'GluCTC. Using synthetic tRF mimics we showed this system was linear over 9 orders of magnitude with sub-attomolar limits of detection. Specificity was tested using naturally occurring mismatched tRF mimics. Finally, we quantified tRF levels in patient plasma and showed that our detection system recapitulates results obtained by qPCR. We have designed a tRF detection system with high sensitivity and specificity capable of quantifying tRFs in low volumes of plasma using benchtop apparatus. This is an important step in the development of a point-of-care device for quantifying tRFs in whole blood.

Biofouling is a major issue in the field of nanomedicine and consists of the spontaneous and unwanted adsorption of biomolecules on engineered surfaces. In a biological context and referring to nanoparticles (NPs) acting as nanomedicines, the adsorption of biomolecules found in blood (mostly proteins) is known as protein corona. On the one hand, the protein corona, as it covers the NPs' surface, can be considered the biological identity of engineered NPs, because the corona is what cells will "see" instead of the underlying NPs. As such, the protein corona will influence the fate, integrity, and performance of NPs in vivo. On the other hand, the physicochemical properties of the engineered NPs, such as their size, shape, charge, or hydrophobicity, will influence the identity of the proteins attracted to their surface. In this context, the design of coatings for NPs and surfaces that avoid biofouling is an active field of research. The gold standard in the field is the use of polyethylene glycol (PEG) molecules, although zwitterions have also proved to be efficient in preventing protein adhesion and fluorinated molecules are emerging as coatings with interesting properties. Hence, in this review, we will focus on recent examples of anti-biofouling coatings in three main areas, that is, PEGylated, zwitterionic, and fluorinated coatings., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: In May 2018, the Irish Constitution was changed following a referendum allowing termination of pregnancy by abortion. It is envisaged that the majority of terminations will be by medical abortion and will take place in general practice before 12 weeks gestation., Aim: To elicit attitudes and level of preparedness of Irish GPs to provide medical abortion services., Design & Setting: Cross-sectional study of 222 GPs who were associated with the University of Limerick Graduate Entry Medical School (GEMS) and GP training programme., Method: An anonymous online questionnaire was distributed via email. Reminders were sent 2 and 4 weeks later., Results: The response rate was 57.2% ( n = 127/222). Of the responders, 105 (82.7%) had no training in this area, with only 4 (3.1%) indicating that they had sufficient training. Nearly all responders ( n = 119, 93.7%) were willing to share abortion information with patients. Just under half of responders ( n = 61, 48.0%) would be willing to prescribe abortion pills, with 47 (37.0%) unwilling to do so. Only 53 (41.7%) responders believed that provision of abortion services should be part of general practice, with 52 (40.9%) saying that it should not. As to whether doctors should be entitled to a conscientious objection but should also be obliged to refer the patient, 92 (72.4%) responders agreed. Over two-thirds of responders ( n = 89, 70.1%) felt that necessary patient support services are not currently available., Conclusion: There is a lack of training and a considerable level of unwillingness to participate in this process among Irish GPs. There is also a perceived lack of patient support services for women experiencing unwanted pregnancy. It is incumbent upon state and professional bodies to address these issues., (Copyright © 2019, The Authors.)

The need for practical biomarkers for early diagnosis of Alzheimer's disease (AD) remains largely unmet. Here we investigated the use of blood-based microRNAs as prognostic biomarkers for AD and their application in a novel electrochemical microfluidic device for microRNA detection. MicroRNA transcriptome was profiled in plasma from patients with mild cognitive impairment (MCI) and AD. MicroRNAs Let-7b and microRNA-206 were validated at elevated levels in MCI and AD, respectively. MicroRNA-206 displayed a strong correlation with cognitive decline and memory deficits. Longitudinal follow-ups over five years identified microRNA-206 increases preceding the onset of dementia. MicroRNA-206 was increased in unprocessed plasma of AD and MCI subjects, detected by our microfluidic device. While increased Let-7b levels in plasma may be used to identify patients with MCI, changes in plasma levels of microRNA-206 may be used to predict cognitive decline and progression towards dementia at an MCI stage. MicroRNA quantification via a microfluidic device could provide a practical cost-effective tool for the stratification of patients with MCI according to risk of developing AD.

Axon pathfinding and synapse formation are essential processes for nervous system development and function. The assembly of myelinated fibres and nodes of Ranvier is mediated by a number of cell adhesion molecules of the immunoglobulin superfamily including neurofascin, encoded by the NFASC gene, and its alternative isoforms Nfasc186 and Nfasc140 (located in the axonal membrane at the node of Ranvier) and Nfasc155 (a glial component of the paranodal axoglial junction). We identified 10 individuals from six unrelated families, exhibiting a neurodevelopmental disorder characterized with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement, who were found by exome or genome sequencing to carry one frameshift and four different homozygous non-synonymous variants in NFASC. Expression studies using immunostaining-based techniques identified absent expression of the Nfasc155 isoform as a consequence of the frameshift variant and a significant reduction of expression was also observed in association with two non-synonymous variants affecting the fibronectin type III domain. Cell aggregation studies revealed a severely impaired Nfasc155-CNTN1/CASPR1 complex interaction as a result of the identified variants. Immunofluorescence staining of myelinated fibres from two affected individuals showed a severe loss of myelinated fibres and abnormalities in the paranodal junction morphology. Our results establish that recessive variants affecting the Nfasc155 isoform can affect the formation of paranodal axoglial junctions at the nodes of Ranvier. The genetic disease caused by biallelic NFASC variants includes neurodevelopmental impairment and a spectrum of central and peripheral demyelination as part of its core clinical phenotype. Our findings support possible overlapping molecular mechanisms of paranodal damage at peripheral nerves in both the immune-mediated and the genetic disease, but the observation of prominent central neurological involvement in NFASC biallelic variant carriers highlights the importance of this gene in human brain development and function., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: The assessment and management of prisoners on hunger strikes in a custodial setting is complex. There is limited clinical guidance available for psychiatrists to draw upon in such cases. The purpose of this paper is to develop a management algorithm through expert elicitation to inform the psychiatric care of prisoners on a hunger strike., Design/methodology/approach: A Delphi method was used to elicit views from Irish forensic psychiatrists, a legal expert and an expert in ethics using a structured questionnaire. Themes were extracted from the results of the questionnaire to propose a management algorithm. A consensus was reached on management considerations., Findings: Five consultant forensic psychiatrists, a legal expert and an expert on psychiatric ethics ( n=7) consented to participation, with a subsequent response rate of 71.4 per cent. Consensus was achieved on a proposed management algorithm. Assessment for mental disorder, capacity to refuse food and motivation for food refusal are seen as key psychiatric tasks. The need to work closely with the prison general practitioner and the value of multidisciplinary working and legal advice are described. Relevant aspects of law included mental health, criminal law (insanity) and capacity legislation., Originality/value: This study outlines a management algorithm for the psychiatric assessment and management of prisoners on a hunger strike, a subject about which there is limited guidance to date. Although written from an Irish perspective, this study outlines key considerations for psychiatrists in keeping with international guidance and therefore may be generalisable to other jurisdictions.

An electrochemical biosensor for the detection of cardiac troponin I, cTnI, an important cardiac biomarker, is described. A combination of a novel monoclonal antibody, mAb20B3, and a novel Ir(III)-based metal complex was used for detection using faradaic electrochemical impedance spectroscopy. A limit of detection of 10 ag/mL was achieved, which is significantly lower than established assays. The ability to detect these ultralow concentrations enables rapid and early stage detection of cardiac events and opens up the possibility of developing a point-of-care device., Competing Interests: The authors declare no competing financial interest.

Background: There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable detection in biofluids. Altered levels of circulating microRNAs have been reported in human epilepsy, but most studies collected samples from one clinical site, used a single profiling platform or conducted minimal validation., Method: Using a case-control design, we collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated findings in a large (>250) cohort of samples that included patients with psychogenic non-epileptic seizures (PNES)., Findings: After profiling and validation, we identified miR-27a-3p, miR-328-3p and miR-654-3p with biomarker potential. Plasma levels of these microRNAs were also changed in a mouse model of TLE but were not different to healthy controls in PNES patients. We determined copy number of the three microRNAs in plasma and demonstrate their rapid detection using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Analysis of the microRNAs within the exosome-enriched fraction provided high diagnostic accuracy while Argonaute-bound miR-328-3p selectively increased in patient samples after seizures. In situ hybridization localized miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics predicted targets linked to growth factor signaling and apoptosis., Interpretation: This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Intimate partner violence (IPV) is a major social problem and public health issue, but we still have a relatively small amount of data about partner violence in women with disabilities. The main objective of this study was to understand the experiences of women with disabilities who are or have been abused by their partners and to explore the knowledge, views and training requirements of primary care professionals., Method: Qualitative study using semi-structured interviews with women with disabilities who had experienced IPV (n = 14), and focus groups with healthcare professionals (n = 16)., Results: Women with disabilities suffer specific forms of abuse. Because they depend on the people around them to take action, they are subordinate and this can prolong the abuse. The healthcare staff frequently mentioned that it is often difficult to notice that women with disabilities are being abused. Their lack of training about disabilities and gender-based violence makes them less sure of their ability to identify and deal with any possible cases of abuse., Conclusions: The difficulties described by the women interviewed are broadly speaking the same as those described by the healthcare professionals consulted. A number of suggestions for improvements are provided based on the results found. Implications for Rehabilitation The rehabilitation of abused disabled women implies that women perceive the health system as a resource to resolve their situation. Healthcare professionals should be trained on how to detect, treat and communicate with disabled women who experience partner violence. Is needed to establish a comprehensive system of coordination between services involved in caring for abused women and with disabilities.

Introduction: Social media developments have completely changed how information is accessed and communicated. While great potential exists with these platforms, recent reports of online unprofessional behavior by doctors has threatened the medical professional identity; a matter of critical importance for clinicians and medical educators. This paper outlines a role for social media in facilitating support for clinicians and medical teachers; it will raise awareness of pitfalls and explain ethical and legal guidelines., Methods: An analysis of inappropriate behaviors and conflicting attitudes regarding what is acceptable in online posts, including the inter-generational contrast in online presence and perceptions of where the boundaries lie., Results and Discussion: Guidance documents are analyzed and potentially confusing and conflicting statements are identified and clarified. The authors believe that clinicians and medical students must follow ethical imperatives in both personal and professional spheres., Conclusions: It is essential that medical educational and professional bodies encourage clinicians to support one another and share information online while providing clear legal and ethical advice on maintaining standards and avoiding common pitfalls. Education on the responsible use of social media and associated risk awareness should be a priority for medical school curricula.

Human blood platelets and SK-N-AS neuroblastoma cancer-cell capture at spontaneously adsorbed monolayers of fibrinogen-binding motifs, GRGDS (generic integrin adhesion), HHLGGAKQAGDV (exclusive to platelet integrin α IIb β 3 ), or octanethiol (adhesion inhibitor) at planar gold and ordered 1.6 μm diameter spherical cap gold cavity arrays were compared. In all cases, arginine/glycine/aspartic acid (RGD) promoted capture, whereas alkanethiol monolayers inhibited adhesion. Conversely only platelets adhered to alanine/glycine/aspartic acid (AGD)-modified surfaces, indicating that the AGD motif is recognized preferentially by the platelet-specific integrin, α IIb β 3 . Microstructuring of the surface effectively eliminated nonspecific platelet/cell adsorption and dramatically enhanced capture compared to RGD/AGD-modified planar surfaces. In all cases, adhesion was reversible. Platelets and cells underwent morphological change on capture, the extent of which depended on the topography of the underlying substrate. This work demonstrates that both the nature of the modified interface and its underlying topography influence the capture of cancer cells and platelets. These insights may be useful in developing cell-based cancer diagnostics as well as in identifying strategies for the disruption of platelet cloaks around circulating tumor cells.

Diagnosis of seizure disorders such as epilepsy currently relies on clinical examination and electroencephalogram recordings and is associated with substantial mis-diagnosis. The miRNA, miR-134 (MIR134 in humans), has been found to be elevated in brain tissue after experimental status epilepticus and in human epilepsy cells and their detection in biofluids may serve as unique biomarkers. miRNAs from unprocessed human plasma and human cerebrospinal fluid samples were used in a novel electrochemical detection based on electrocatalytic platinum nanoparticles inside a centrifugal microfluidic device where the sandwich assay is formed using an event triggered release system, suitable for the rapid point-of-care detection of low abundance biomarkers of disease. The device has the advantage of controlling the rotation speed of the centrifugal device to pump nanoliter volumes of fluid at a set time and manipulate the transfer of liquids within the device. The centrifugal platform improves reaction rates and yields by proposing efficient mixing strategies to overcome diffusion-limited processes and improve mass transport rates, resulting in reduced hybridization times with a limit of detection of 1 pM target concentration. Plasma and cerebrospinal fluid samples (unprocessed) from patients with epilepsy or who experienced status epilepticus were tested and the catalytic response obtained was in range of the calibration plot. This study demonstrates a rapid and simple detection for epilepsy biomarkers in biofluid.

Defects within a self-assembled monolayer (SAM) of dodecanethiol on gold have been used as nucleation sites for the electrodeposition of mushroom shaped platinum nanoparticles (PtNPs). The top surfaces of these PtNPs were then decorated with a layer of silver creating a hemispherical - platinum : silver core : shell nanoparticle (Pt-AgNP). Thiolated probe strand miRNA was then immobilised onto the upper silver surface. These regioselectively modified particles were desorbed by applying a current jump to yield nanoparticles capable of hybridising to a complementary miRNA target with electrocatalysis occurring on the non-functionalized lower surface. A second electrode was functionalized with single stranded capture miRNA that has a sequence that is complementary to an miRNA, miR-132, associated with the childhood cancer, Neuroblastoma but leaves a section of the target available to bind the nucleic acid sequence on the core : shell Pt-AgNPs. Following hybridization of the target and capture strands the surface was exposed to the miRNA labelled electrocatalytic Pt-AgNPs. The concentration of the target was then determined by monitoring the current associated with the reduction of hydrogen peroxide in a solution of H 2 SO 4 . Calibration plots of the log[miRNA] vs. faradaic current were linear from 1 aM to 1 μM and aM concentrations could be detected without the need for chemical amplification of the target, e.g., using PCR or NASBA. The regioselectively modified particles were also immobilised within the interior of gold microcavity arrays via miRNA hybridisation and their Raman properties investigated.

Ordered spherical cap gold cavity arrays with 5.4, 1.6, and 0.98 μm diameter apertures were explored as capture surfaces for human blood platelets to investigate the impact of surface geometry and chemical modification on platelet capture efficiency and their potential as platforms for surface enhanced Raman spectroscopy of single platelets. The substrates were chemically modified with single-constituent self-assembled monolayers (SAM) or mixed SAMs comprised of thiol-functionalized arginine-glycine-aspartic acid (RGD, a platelet integrin target) with or without 1-octanethiol (adhesion inhibitor). As expected, platelet adhesion was promoted and inhibited at RGD and alkanethiol modified surfaces, respectively. Platelet adhesion was reversible, and binding efficiency at the peptide modified substrates correlated inversely with pore diameter. Captured platelets underwent morphological change on capture, the extent of which depended on the topology of the underlying substrate. Regioselective capture of the platelets enabled study for the first time of the surface enhanced Raman spectroscopy of single blood platelets, yielding high quality Raman spectroscopy of individual platelets at 1.6 μm diameter pore arrays. Given the medical importance of blood platelets across a range of diseases from cancer to psychiatric illness, such approaches to platelet capture may provide a useful route to Raman spectroscopy for platelet related diagnostics.

Highly sensitive and label free detection of prostate specific antigen (PSA) still remains a challenge in prostate cancer diagnosis. In this paper, we propose a sensitive electrochemical immunosensor based on electrocatalytic platinum nanoparticles conjugated to a recombinant scFv antibody. Gold disc electrodes functionalised with a l-Cysteine (Cys) self-assembled monolayer (SAM) were used to covalently bind PSA specific monoclonal antibody (anti-PSA) using N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) chemistry. Immunosensing was completed using sandwich-type immunoreaction of the PSA-antigen (1-30 ng/mL) between anti-PSA immobilized on the l-Cys modified electrode using label free electrochemical impedance (EIS) technique. Furthermore, highly specific in-house generated scFv fragments as receptor proteins were utilised for one step site-directed immobilisation on the surface of platinum nanoparticles (PtNPs). To improve the sensitivity of the immunoassay, these scFV labelled electrocatalytic PtNPs were then used for covalent hybridisation to the PSA modified electrode and then applied in a hybridisation assay to determine the concentration of the PSA by measuring the faradaic current associated with reduction of peroxide in solution. Semi-log plots of the PSA concentration vs. faradaic current are linear from 1 to 30 ng/mL and pM concentrations can be detected without the need for molecular, e.g., PCR or NASBA, amplification., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Gold-Copper core shell nanowires have been electrodeposited and their electrochemical and Raman properties probed. First, hollow copper nanotubes, 3.2 ± 0.1 μm long, with a uniform diameter of 70 ± 22 nm, were electrodeposited within the pores of a track etched polycarbonate membrane filter. Second, gold was then electrodeposited within these copper cylinders to yield the gold-copper core-shell nanowires. Nanowires, functionalised with probe strand DNA, that is complementary to that of the pathogen Staph. Aureus, only on their ends, can be immobilised onto an electrode surface in a DNA sandwich assay. Significantly, the charge associated with the selective oxidation of the copper shell depends linearly on the target DNA concentration from 1 nM to 100 μM.

Blood platelet adhesion is crucial in dictating haemocompatibility of medical implants and in platelet capture in diagnostics. Understanding the role of platelet activation in dictating platelet adhesion at chemically modified interfaces is important but relatively unexplored. Using scanning electron microscopy and confocal fluorescence microscopy a quantitative assessment of capture of blood platelets at self-assembled monolayers and mixed monolayers (SAMs) on gold as a function of the activation status of the platelets was conducted. Single and mixed monolayers were prepared using thiol-functionalized arginine-glycine-aspartic acid (RGD), C-Ahx-GRGDS (Ahx = aminohexanoic acid linker), thiolated poly(ethylene)glycol (PEG-COOH) and 1-octanethiol. When incubated with suspensions of resting platelets, RGD promoted platelet adhesion compared to bare or alkanethiol modified gold. Increasing the alkanethiol ratio in the deposition solution decreased the extent of platelet adhesion. Platelet adhesion increased approximately 3 fold at PEG-COO- modified surfaces compared to RGD-alone. Platelets adhered to RGD or mixed RGD : alkane SAM surfaces were found to be captured in their resting state. In contrast, platelets captured at PEG-COO- SAM surfaces were activated by these substrates. The effect of treating platelets with the chemical activators, Mn 2+ or DTT or the physiological activator, thrombin, on the capture efficiency and activation at RGD modified surfaces was also investigated. Mn 2+ treated platelets presented similar adhesion to untreated platelets, while surprisingly DTT yielded a very significant decrease in platelet adhesion. And, any platelets that were captured, were in a resting state. Thrombin activated platelets were captured with similar efficiencies as untreated platelets. However, the platelets captured were fully activated. The distinction between capture of chemically and physiologically activated platelet is interesting and likely to originate from differences in the conformation of the integrin induced by each process. Finally, platelet adhesion to each surface could be reversed by incubation with a solution of linear or cyclical RGD or PEG-COO- for the RGD and PEGCOO- surfaces respectively. The specificity of platelet removal confirmed that platelet adhesion at RGD surfaces is occurring through integrin-RGD interactions.

Suspensions of electrocatalytic platinum nanoparticles with radii as small as 78.9 ± 3.5 nm that are functionalised with DNA only in one region have been created using templated electrodeposition. The integrity of the bound DNA following nanoparticle desorption from the electrode is demonstrated by detecting attomolar concentrations of DNA without the need for molecular, e.g., PCR or NASBA, amplification. Double potential step approaches coupled with interface engineering via nucleation sites allows PtNPs to be created with controlled particle size and density in a facile and reproducible manner.

Poly-3,4-ethylenedioxythiophene, PEDOT, films have been deposited on gold electrodes using polymerization from the vapor-phase in which the surface is first covered with a Fe (III) tosylate oxidant and then exposed to 3,4-ethylenedioxythiophene, EDOT, vapor. Gold nanoparticles were then electrodeposited to give a nanocomposite material, PEDOT-AuNP. Thiolated capture strand DNA, that is complementary to the sequence associated with the pathogen S. aureus that causes mammary gland inflammation, was then immobilized onto the gold nanoparticles and the underlying gold electrode. The target oligo was then hybridized to the capture strand DNA. A probe strand, labeled with horse radish peroxidase, was then hybridized to the target. The concentration of the target was determined by measuring the current required to reduce hydroquinone oxidized during the regeneration of the HRP label. Semi-log plots of the pathogen DNA concentration vs. faradaic current are linear from 150 pM to 1 μM and pM concentrations can be detected without the need for molecular, e.g., PCR or NASBA, amplification., (Copyright © 2012. Published by Elsevier B.V.)

Platinum nanoparticles, functionalised regioselectively with probe strand DNA, have been immobilised within the interior of gold nanocavity arrays via DNA hybridisation. The immobilised nanoparticles are highly electrocatalytic and show significantly higher currents for the reduction of hydrogen peroxide than uniformly functionalised particles.

Self-assembled monolayers (SAMs) of dodecanethiol have been formed on gold electrodes to produce nanoscale defects. These defects define nucleation sites for the electrodeposition of mushroom shaped platinum nanoparticles (PtNPs). The top surfaces of these PtNPs have been selectively functionalized with single stranded probe DNA. These regioselectively modified particles were desorbed by applying a current jump to yield nanoparticles capable of biorecognition on the top curved side and efficient electrocatalysis on the nonfunctionalized lower surface. A second electrode was functionalized with single stranded capture DNA that has a sequence that is complementary to the pathogen, Staphylococcus aureus but leaves a section of the target available to bind the probe strand immobilized on the PtNPs. Following hybridization of the target and capture strands, the surface was exposed to the probe DNA labeled electrocatalytic PtNPs. Target binding was detected by monitoring the current associated with the reduction of hydrogen peroxide in a solution of 0.01 M H(2)SO(4). Calibration plots of the log[DNA] versus faradaic current were linear from 10 pM to 1 μM and picomolar concentrations could be detected without the need for amplification of the target, for example, using PCR or NASBA. As well as a wide dynamic range, this detection strategy has an excellent ability to discriminate DNA mismatches and a high analytical sensitivity.

Suspensions of electrocatalytic gold nanoparticles with radii as small as 83 ± 13 nm that are functionalised with DNA only in one region have been created using templated electrodeposition. The integrity of the bound DNA following nanoparticle desorption from the electrode is demonstrated by detecting picomolar concentrations of DNA without the need for molecular, e.g., PCR or NASBA, amplification., (This journal is © The Royal Society of Chemistry 2012)

Polyaniline (PANI) nanofibres (PANI-NF) have been modified with chemically grown gold nanoparticles to give a nanocomposite material (PANI-NF-AuNP) and deposited on gold electrodes. Single stranded capture DNA was then bound to the gold nanoparticles and the underlying gold electrode and allowed to hybridise with a complementary target strand that is uniquely associated with the pathogen, Staphylococcus aureus (S. aureus), that causes mastitis. Significantly, cyclic voltammetry demonstrates that deposition of the gold nanoparticles increases the area available for DNA immobilisation by a factor of approximately 4. EPR reveals that the addition of the Au nanoparticles efficiently decreases the interactions between adjacent PANI chains and/or motional broadening. Finally, a second horseradish peroxidase (HRP) labelled DNA strand hybridises with the target allowing the concentration of the target DNA to be detected by monitoring the reduction of a hydroquinone mediator in solution. The sensors have a wide dynamic range, excellent ability to discriminate DNA mismatches and a high sensitivity. Semi-log plots of the pathogen DNA concentration vs. faradaic current were linear from 150×10(-12) to 1×10(-6) mol L(-1) and pM concentrations could be detected without the need for molecular, e.g., PCR or NASBA, amplification., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The purpose of this study is to report toxicity and outcome results in patients with gynaecological tumours treated with a final boost using extra-cranial stereotactic radiotherapy (SRT) with a linac-based micro-multileaf collimator technique as an alternative to high-dose rate brachytherapy (HDR-BT). Since January 2002, 26 patients with either endometrial (n = 17) or cervical (n = 9) cancer were treated according to this protocol: 45-50.4 Gy external radiotherapy (RT) to the pelvic +/- para-aortic regions followed by a final SRT boost of 2 x 7 Gy to the vaginal vault (4-7 day interval between fractions). Median age was 62 years (37-74 range). Fifteen patients were diagnosed with adenocarcinoma, 7 with squamous-cell carcinoma, and 4 with sarcoma. FIGO stage I (n = 17), stage II (n = 7), and stage III (n = 2). Toxicity was scored according to RTOG/EORTC criteria. No severe (> grade-3) acute urinary or low-gastrointestinal (GI) toxicity was observed during treatment and up to 3 months after treatment completion. Moderate (grade < or = 3) acute urinary or low-GI toxicity was observed in 23% and 35% of patients, respectively. After a median follow-up of 47 months (4-77, range), late urinary, low-GI, and sexual > or = grade-2 (worst score) has been reported in 4%, 12% and 29.4% of patients, respectively. The 3-year loco-regional failure-free and overall survival rates were 96% and 95%, respectively. Preliminary results on feasibility, tolerance, and outcome with SRT are encouraging and may be considered a sound alternative to HDR-BT for gynecologic tumors.

Two samples of patients suffering from senile dementia were administered the Kew tests for parietal lobe function and aphasia. No evidence emerged of any clinical heterogeneity; parietal lobe test performance was found to be more a function of degree of impairment rather than of age.

The broad host range streptococcal plasmid pLS1 encodes for a 5.1-kDa repressor protein, RepA. This protein has affinity for DNA (linear or supercoiled) and is translated from the same mRNA as the replication initiator protein RepB. By gel retardation assays, we observed that RepA shows specificity for binding to the plasmid HinfID fragment, which includes the target of the protein. The target of RepA within the plasmid DNA molecule has been located around the plasmid single site ApaLI. This site is included in a region that contains the promoter for the repA and repB genes and is contiguous to the plasmid ori(+). A complex sequence-directed DNA curvature is observed in this region of pLS1. Upon addition of RepA to plasmid linear DNA or to circularly permuted restriction fragments, this intrinsic curvature was greatly enhanced. Thus, a strong RepA-induced bending could be located in the vicinity of the ApaLI site. Visualization of the bent DNA was achieved by electron microscopy of complexes between RepA and plasmid DNA fragments containing the RepA target.