CV13014

Use the URI link below to search the Marine Institute Data Discovery Catalogue for datasets relevant to this report.This report provides the main results of the 2013 underwater television survey on the ‘Labadie, Jones and Cockburn Banks’ ICES assessment area; Functional Unit 20-21. Some exploratory stations were carried out in 2006 and 2012. The survey was multi-disciplinary in nature collecting UWTV, CTD, Multibeam and other ecosystem data. A randomised isometric grid design was employed with UWTV stations at 6.0 nmi intervals. Due to weather and technical downtime only 58 out of the 95 planned stations were successfully completed. The adjusted mean density for 2013 was 0.18/m2 which can be classified as “low density”. Scientific knowledge of the heterogeneous habitat and spatial distribution of the Nephrops population in this area is developing. Survey design and burrow identification are particularly difficult in this area due to factors discussed. The occurrence of sea-pens and trawl marks on the UWTV footage is also presented

C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies

OBJECTIVE: In many cases where Huntington disease (HD) is suspected, the genetic test for HD is negative: these are known as HD phenocopies. A repeat expansion in the C9orf72 gene has recently been identified as a major cause of familial and sporadic frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Our objective was to determine whether this mutation causes HD phenocopies. METHODS: A cohort of 514 HD phenocopy patients were analyzed for the C9orf72 expansion using repeat primed PCR. In cases where the expansion was found, Southern hybridization was performed to determine expansion size. Clinical case notes were reviewed to determine the phenotype of expansion-positive cases. RESULTS: Ten subjects (1.95%) had the expansion, making it the most common identified genetic cause of HD phenocopy presentations. The size of expansion was not significantly different from that associated with other clinical presentations of C9orf72 expanded cases. The C9orf72 expansion-positive subjects were characterized by the presence of movement disorders, including dystonia, chorea, myoclonus, tremor, and rigidity. Furthermore, the age at onset in this cohort was lower than previously reported for subjects with the C9orf72 expansion and included one case with pediatric onset. DISCUSSION: This study extends the known phenotype of the C9orf72 expansion in both age at onset and movement disorder symptoms. We propose a revised clinico-genetic algorithm for the investigation of HD phenocopy patients based on these data

Assessing the influence of the Responsibility to Protect on the UN Security Council during the Arab Spring

This article challenges those perspectives which assert first, that the Security Council’s engagement with the Responsibility to Protect (R2P) during the Arab Spring evidences a generally positive trend, and second, that the response to the Arab Spring, particularly Syria, highlights the need for veto restraint. With respect to the first point, the evidence presented in this article suggests that the manner in which R2P has been employed by the Security Council during this period evidences three key trends: first, a willingness to invoke R2P only in the context of Pillar I; second, a pronounced lack of consensus surrounding Pillar III; and third, the persistent prioritisation of national interests over humanitarian concerns. With respect to veto restraint, this article argues that there is no evidence that this idea will have any significant impact on decision-making at the Security Council; the Council’s response to the Arab Spring suggests that national interests continue to trump humanitarian need

Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial

Importance: Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported that ambroxol increases β-glucocerebrosidase (GCase) enzyme activity and reduces α-synuclein levels. These observations support a potential role for ambroxol therapy in modifying a relevant pathogenetic pathway in PD. Objective: To assess safety, tolerability, cerebrospinal fluid (CSF) penetration, and target engagement of ambroxol therapy with GCase in patients with PD with and without GBA1 mutations. / Interventions: An escalating dose of oral ambroxol to 1.26 g per day. Design, Setting, and Participants: This single-center open-label noncontrolled clinical trial was conducted between January 11, 2017, and April 25, 2018, at the Leonard Wolfson Experimental Neuroscience Centre, a dedicated clinical research facility and part of the University College London Queen Square Institute of Neurology in London, United Kingdom. Participants were recruited from established databases at the Royal Free London Hospital and National Hospital for Neurology and Neurosurgery in London. Twenty-four patients with moderate PD were evaluated for eligibility, and 23 entered the study. Of those, 18 patients completed the study; 1 patient was excluded (failed lumbar puncture), and 4 patients withdrew (predominantly lumbar puncture-related complications). All data analyses were performed from November 1 to December 14, 2018. / Main Outcomes and Measures: Primary outcomes at 186 days were the detection of ambroxol in the CSF and a change in CSF GCase activity. / Results: Of the 18 participants (15 men [83.3%]; mean [SD] age, 60.2 [9.7] years) who completed the study, 17 (8 with GBA1 mutations and 9 without GBA1 mutations) were included in the primary analysis. Between days 0 and 186, a 156-ng/mL increase in the level of ambroxol in CSF (lower 95% confidence limit, 129 ng/mL; P < .001) was observed. The CSF GCase activity decreased by 19% (0.059 nmol/mL per hour; 95% CI, -0.115 to -0.002; P = .04). The ambroxol therapy was well tolerated, with no serious adverse events. An increase of 50 pg/mL (13%) in the CSF α-synuclein concentration (95% CI, 14-87; P = .01) and an increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% CI, 40-137; P = .002) were observed. Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, -10.4 to -3.1; P = .001). These changes were observed in patients with and without GBA1 mutations. / Conclusions and Relevance: The study results suggest that ambroxol therapy was safe and well tolerated; CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased. Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD. Trial Registration: ClinicalTrials.gov identifier: NCT02941822; EudraCT identifier: 2015-002571-24

Everyday legitimacy and international administration: global governance and local legitimacy in Kosovo

International administrations are a very specific form of statebuilding. This paper examines the limits illustrated by the experience in Kosovo. Here, the international administration faced the same requirements of any legitimate, Liberal government, but without the checks and balances normally associated with Liberal governance. Thus, the international administration was granted full authority and the power thereby associated, but without the legitimacy upon which the Liberal social contract rests. The state-building agenda put forth came to be seen as more exogenous, reinforcing the delegitimization process. This paper will specifically address the influence of the Weberian approach to legitimacy on the statebuilding literature, as well as its limits. It will then propose other possible avenues for statebuilding, more in line with a wider understanding of legitimacy and intervention

CV13016

Use the URI link below to search the Marine Institute Data Discovery Catalogue for datasets relevant to this report.This report provides the results of the second underwater television on the ‘Porcupine Bank Nephrops grounds’ ICES assessment area; Functional Unit 16. The survey was multi-disciplinary in nature collecting UWTV, CTD and other ecosystem data. In total 68 UWTV stations were successfully completed in a randomised 6 nautical mile isometric grid covering the full spatial extent of the stock. The mean burrow density observed in 2013, adjusted for edge effect, was 0.106 burrows/m². The final krigged abundance estimate was 768 million burrows with a relative standard error of 4% and an estimated stock area of 7,100km2. The abundance estimate was 2% lower than in 2012. Landings options at various different fishing mortalities were calculated in line with the recommendations of WKNEPH 2013. Fishing at Fmsy in 2014 implies a slight increase in the TAC from 1,800 t to 1,850 t. This increase is mainly due to an increase in average mean weight of the landings. The three species of sea-pen found on muddy habitat in Irish waters are Virgularia mirabilis, Funiculina quadrangularis and Pennatula phosphorea were all observed during the survey. Trawl marks were also observed on over half of the stations surveyed

CV13015

Use the URI link below to search the Marine Institute Data Discovery Catalogue for datasets relevant to this report.This report provides the main results and findings of the fourth underwater television survey of the various Nephrops grounds in Functional Unit 19. The survey was multi-disciplinary in nature collecting UWTV, CTD, multi-beam and other ecosystem data. In 2013 a total 40 UWTV stations were successfully completed. Adjusted burrow density estimates varied considerably across the different grounds. The 2013 raised abundance estimate of 397 million burrows is a 20% decrease from the 2012 estimate. Taking into account the uncertainty (CV of 17%) this is not significantly different from abundance estimates in 2011 or 2012. Using the 2013 abundance and recent mean weight and discard implies 2014 total catch advice fishing at Fmsy (=F35%spr) of 618 tonnes which results in landings of no more than 521 tonnes