Politics and poor weather: how Ireland sued the UK under the European Convention on Human Rights

This paper, which has been prepared as part of a larger research project, examines the deliberations of the Irish Government from the time internment in Northern Ireland was introduced, on 9 August 1971, to the submission of the application by the Irish government on 16 December of that year. It considers how the decision to submit an application to the European Commission of Human Rights became an increasing inevitability; and appears to have been recognised as such by British Prime Minister Edward Heath. With the decision of the British Government to establish the Compton Committee, in September 1971, the arena turned to bilateral consultations between Taoiseach (Prime Minister) Jack Lynch and British Prime Minister Edward Heath. When these broke down, the Irish Government let Heath know it was ‘seriously considering’ submitting an inter-State application. A final decision was taken by the Irish Cabinet on 30 November 1971 and the filed two weeks later

Increased lymph node yield in colorectal cancer is not necessarily associated with a greater number of lymph node positive cancers

Peer reviewedPublisher PD

Attempted DNA extraction from a Rancho La Brea Columbian mammoth (Mammuthus columbi): prospects for ancient DNA from asphalt deposits.

Fossil-bearing asphalt deposits are an understudied and potentially significant source of ancient DNA. Previous attempts to extract DNA from skeletons preserved at the Rancho La Brea tar pits in Los Angeles, California, have proven unsuccessful, but it is unclear whether this is due to a lack of endogenous DNA, or if the problem is caused by asphalt-mediated inhibition. In an attempt to test these hypotheses, a recently recovered Columbian mammoth (Mammuthus columbi) skeleton with an unusual pattern of asphalt impregnation was studied. Ultimately, none of the bone samples tested successfully amplified M. columbi DNA. Our work suggests that reagents typically used to remove asphalt from ancient samples also inhibit DNA extraction. Ultimately, we conclude that the probability of recovering ancient DNA from fossils in asphalt deposits is strongly (perhaps fatally) hindered by the organic compounds that permeate the bones and that at the Rancho La Brea tar pits, environmental conditions might not have been ideal for the general preservation of genetic material

Role of the DNA Sensor STING in Protection from Lethal Infection following Corneal and Intracerebral Challenge with Herpes Simplex Virus 1

STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal to STING(-/-) mice by the i.v. route. Corneally infected STING(-/-) mice also showed increased periocular disease and increased corneal and trigeminal ganglia titers, although there was no difference in brain titers. They also showed elevated expression of tumor necrosis factor alpha (TNF-α) and CXCL9 relative to control mice but surprisingly modest changes in type I interferon expression. Finally, we also showed that HSV strains lacking the ability to counter autophagy and the PKR-driven antiviral state had near-wild-type virulence following intracerebral infection of STING(-/-) mice. Together, these data show that while STING is an important component of host resistance to HSV in the cornea, its previously shown immutable role in mediating host survival by the i.v. route was not recapitulated following a mucosal infection route. Furthermore, our data are consistent with the idea that HSV counters STING-mediated induction of the antiviral state and autophagy response, both of which are critical factors for survival following direct infection of the nervous system

Mutation update for the \u3cem\u3eSATB2\u3c/em\u3e gene

SATB2‐associated syndrome (SAS) is an autosomal dominant neurodevelopmental disorder caused by alterations in the SATB2 gene. Here we present a review of published pathogenic variants in the SATB2 gene to date and report 38 novel alterations found in 57 additional previously unreported individuals. Overall, we present a compilation of 120 unique variants identified in 155 unrelated families ranging from single nucleotide coding variants to genomic rearrangements distributed throughout the entire coding region of SATB2. Single nucleotide variants predicted to result in the occurrence of a premature stop codon were the most commonly seen (51/120 = 42.5%) followed by missense variants (31/120 = 25.8%). We review the rather limited functional characterization of pathogenic variants and discuss current understanding of the consequences of the different molecular alterations. We present an expansive phenotypic review along with novel genotype‐phenotype correlations. Lastly, we discuss current knowledge of animal models and present future prospects. This review should help provide better guidance for the care of individuals diagnosed with SAS

Pulse source for 80 Gb/s systems using a gain-wwitched laser diode followed by a nonlinearly chirped grating

This work presents the generation of 3.5 ps pulses at a repetition rate of 10 GHz and the optimization of the pulse spectrum. The output pulses are near transform limited and have pulse pedestals that are virtually eliminated to 35 dB down from the peak of the pulse, thus providing a source suitable for use in 80 Gb/s OTDM systems

Development of an intervention to improve the management of behavioural and psychological symptoms of dementia in general practice in Ireland

Background General practitioners (GPs) play a pivotal and increasing role in the care of people with dementia. However, GPs are challenged by the complexities of dementia care. A triangulated educational needs analysis conducted by the PREPARED project identified that GPs find the management of behavioural and psychological symptoms of dementia (BPSD) a particularly challenging aspect of dementia care. BPSD encompasses a wide range of non-cognitive symptoms such as anxiety and hallucinations that affect people with dementia. Although BPSD has been identified as a challenging area for GPs, an area in which they lack confidence, we do not have a good understanding of why this is a challenging area for GPs or the root causes of their lack of confidence. Furthermore, evidence suggests that current management of BPSD is sub-optimal. In BPSD non-pharmacological strategies are recommended first-line but uptake of these strategies is low. Despite their adverse effects, potentially harmful pharmacological treatments, such as antipsychotics, are frequently employed. Interventions are needed to improve the management of BPSD. It is apposite that these interventions should target GPs. However, interventions to date to improve the management of BPSD have either not targeted GPs or not effectively involved GPs in intervention development, a notable gap in the literature. Aim To enhance our understanding of the management of BPSD in general practice with a view to informing a theoretically-based, behaviour change intervention to improve the management of BPSD. Methods This was a mixed methods study underpinned by the UK Medical Research Council (MRC) guidance on the development of complex interventions in health care. Existing evidence on GPs’ knowledge of, attitudes towards and experiences with BPSD was systematically reviewed using a mixed methods approach and synthesised using meta-ethnography. Findings of this review were supplemented with new evidence from three studies. A descriptive interpretive qualitative study which explored GPs experiences of managing BPSD. The data collected from 16 semi-structured interviews with a purposively selected sample of GPs were then thematically analysed. The second study was a cross-sectional descriptive study which assessed GPs’ knowledge of and attitudes towards pain in dementia, a key trigger for BPSD. In this study, a postal questionnaire was sent to a census sample of all GPs in Cork. The results were statistically analysed to explore associations between demographic data and responses. To further investigate the findings of the qualitative study a descriptive cross-sectional study was conducted that aimed to explore the knowledge and attitudes of GPs to the prescribing of antipsychotics in people with dementia. The study used an anonymous postal questionnaires that was sent to a census sample of all GPs based in Cork and Kerry. To develop the intervention, results from the systematic review, the qualitative and the two cross-sectional studies were integrated, using the behavioural change theoretical approach outlined in the Behaviour Change Wheel (BCW). In addition, a modified eDelphi study was conducted with multidisciplinary experts on antipsychotic prescribing in dementia. The eDelphi study helped to achieve consensus on the clinical components of the intervention. Findings The over-arching finding from the systematic review was that a lack of practical, implementable non-pharmacological treatment strategies created a therapeutic void for GPs, which led to over-reliance on family caregivers and on psychotropic medications. In the qualitative study some GPs described the challenges of managing BPSD as insurmountable and many struggled at an ethical level with the decision to prescribe potentially harmful psychotropic medication but felt they had little else to offer. Key challenges identified by GPs were; stretched resources, unrealistic expectations and a lack of implementable clinical guidelines. The cross-sectional descriptive study of GPs’ knowledge of and attitudes towards the management of pain identified aspects of GPs’ management of pain in dementia that could be improved upon and highlighted the importance of good relationships between GP and nursing home staff when managing dementia. The descriptive cross-sectional study of GPs’ attitudes towards antipsychotic prescribing in dementia found that the majority of GPs recommended non-pharmacological strategies first line when managing BPSD. The GPs reported that the main influencers of prescribing antipsychotics in BPSD were nursing staff and family. Of note the majority of respondents did not routinely monitor antipsychotic prescribing in people with dementia Using the approach outlined in the Behaviour Change Wheel the findings of these four studies were used to select an aspect of GPs’ behaviour in the management of BPSD to target with an intervention: ‘GPs to systematically monitor their prescribing of antipsychotic medication to people with dementia in nursing home settings’. To address this behaviour, a three-component intervention was developed, consisting of: an interprofessional educational session with GPs and nursing home staff; a repeat prescribing monitoring tool and the facilitation of a self-audit. Conclusion The research presented in this thesis adds depth to existing literature and advances our knowledge of the management of BPSD in general practice. Prior to this research it was known that GPs found BPSD challenging but the reasons for why GPs found BPSD to be challenging had not been explored. This research offers new insights into GPs’ perspectives on the management of BPSD. This new insight helps to explain apparent discrepancies between best practice recommendations in BPSD and real-life clinical practice. This deeper understanding of GPs’ management of BPSD informed the development of an intervention to improve an aspect of BPSD management that was identified as being sub-optimal. The intervention developed focuses on GP self-monitoring of their prescribing of antipsychotic medication to people with BPSD in nursing home settings. This intervention has the potential to improve GPs’ management of BPSD

Optimized pulse source employing an externally injected gain-switched laser diode in conjunction with a nonlinearly chirped grating

In this paper, we demonstrate the generation of transform-limited short optical pulses, which display excellent spectral and temporal qualities by employing a novel technology, based on an externally injected gain-switched laser in conjunction with a nonlinearly chirped grating. Using this technique, 3.5-ps optical pulses exhibiting a time-bandwidth product (TBP) of 0.45 are generated, which are suitable for use in high-speed 80 Gb/s optical time-division multiplexing (OTDM) communications systems. The numerical integration of a set of rate equations using suitable parameters for the devices used in the experiments were carried out to further confirm the feasibility of the proposed method for developing an optimized pulse source for high-speed photonic systems

80-Gb/s OTDM system analysis of a vertical microcavity-based saturable absorber for the enhancement of pulse pedestal suppression

In future high-speed optical time-division-multiplexed (OTDM) systems, an important factor that needs to be considered for optical pulse generation schemes is the impact of pulse pedestals on the overall system performance. The results presented in this letter are two-fold; first, the impact due to the height of pulse pedestals in an 80-Gb/s OTDM system are established. Second, a solution is provided to overcome these high pedestal levels through the use of a vertical microcavity saturable absorber, which can significantly reduce the pulse pedestal level and give enhanced system performanc