Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system

The giant fiber system (GFS) is a simple network of neurons that mediates visually elicited escape behavior in Drosophila. The giant fiber (GF), the major component of the system, is a large, descending interneuron that relays visual stimuli to the motoneurons that innervate the tergotrochanteral jump muscle (TTM) and dorsal longitudinal flight muscles (DLMs). Mutations in the neural transcript from the shaking-B locus abolish the behavioral response by disrupting transmission at some electrical synapses in the GFS. This study focuses on the role of the gene in the development of the synaptic connections. Using an enhancer-trap line that expresses lacZ in the GFs, we show that the neurons develop during the first 30 hr of metamorphosis. Within the next 15 hr, they begin to form electrical synapses, as indicated by the transfer of intracellularly injected Lucifer yellow. The GFs dye-couple to the TTM motoneuron between 30 and 45 hr of metamorphosis, to the peripherally synapsing interneuron that drives the DLM motoneurons at approximately 48 hr, and to giant commissural interneurons in the brain at approximately 55 hr. Immunocytochemistry with shaking-B peptide antisera demonstrates that the expression of shaking-B protein in the region of GFS synapses coincides temporally with the onset of synaptogenesis; expression persists thereafter. The mutation shak-B2, which eliminates protein expression, prevents the establishment of dye coupling shaking-B, therefore, is essential for the assembly and/or maintenance of functional gap junctions at electrical synapses in the GFS

Pharmacoepidemiology resources in Ireland-an introduction to pharmacy claims data.

INTRODUCTION: Administrative health data, such as pharmacy claims data, present a valuable resource for conducting pharmacoepidemiological and health services research. Often, data are available for whole populations allowing population level analyses. Moreover, their routine collection ensures that the data reflect health care utilisation in the real-world setting compared to data collected in clinical trials. SETTING AND METHODS: The Irish Health Service Executive-Primary Care Reimbursement Service (HSE-PCRS) community pharmacy claims database is described. The availability of demographic variables and drug-related information is discussed. The strengths and limitations associated using this database for conducting research are presented, in particular, internal and external validity. Examples of recently conducted research using the HSE-PCRS pharmacy claims database are used to illustrate the breadth of its use. RESULTS AND CONCLUSIONS: The HSE-PCRS national pharmacy claims database is a large, high-quality, valid and accurate data source for measuring drug exposure in specific populations in Ireland. The main limitation is the lack of generalisability for those aged <70 years and the lack of information on indication or outcome

Prescriber variation in potentially inappropriate prescribing in older populations in Ireland.

BACKGROUND: Health care policy-makers look for prescribing indicators at the population level to evaluate the performance of prescribers, improve quality and control drug costs. The aim of this research was to; (i) estimate the level of variation in potentially inappropriate prescribing (PIP) across prescribers in the national Irish older population using the STOPP criteria; (ii) estimate how reliably the criteria could distinguish between prescribers in terms of their proportion of PIP and; (iii) examine how PIP varies between prescribers and by patient and prescriber characteristics in a multilevel regression model. METHODS: 1,938 general practitioners (GPs) with 338,375 registered patients\u27 ≥70 years were extracted from the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. HSE-PCRS prescriptions are WHO ATC coded. Demographic data for claimants\u27 and prescribers\u27 are available. Thirty STOPP indicators were applied to prescription claims in 2007. Multilevel logistic regression examined how PIP varied between prescribers and by individual patient and prescriber level variables. RESULTS: The unadjusted variation in PIP between prescribers was considerable (median 35%, IQR 30-40%). The STOPP criteria were reliable measures of PIP (average \u3e0.8 reliability). The multilevel regression models found that only the patient level variable, number of different repeat drug classes was strongly associated with PIP (\u3e2 drugs v none; adjusted OR, 4.0; 95% CI 3.7, 4.3). After adjustment for patient level variables the proportion of PIP varied fourfold (0.5 to 2 times the expected proportion) between prescribers but the majority of this variation was not significant. CONCLUSION: PIP is of concern for all prescribers. Interventions aimed at enhancing appropriateness of prescribing should target patients taking multiple medications

Proton pump inhibitors: potential cost reductions by applying prescribing guidelines.

BACKGROUND: There are concerns that proton pump inhibitors (PPI) are being over prescribed in both primary and secondary care. This study aims to establish potential cost savings in a community drug scheme for a one year period according to published clinical and cost-effective guidelines for PPI prescribing. METHODS: Retrospective population-based cohort study in the Republic of Ireland using the Health Services Executive (HSE) Primary Care Reimbursement Services (PCRS) pharmacy claims database. The HSE-PCRS scheme is means tested and provides free health care including medications to approximately 30% of the Irish population. Prescription items are WHO ATC coded and details of every drug dispensed and claimants\u27 demographic data are available. Potential cost savings (net ingredient cost) were estimated according to UK NICE clinical guidelines for all HSE-PCRS claimants on PPI therapy for ≥3 consecutive months starting in 2007 with a one year follow up (n=167,747). Five scenarios were evaluated; (i) change to PPI initiation (cheapest brand); and after 3 months (ii) therapeutic switching (cheaper brand/generic equivalent); (iii) dose reduction (maintenance therapy); (iv) therapeutic switching and dose reduction and (v) therapeutic substitution (H2 antagonist). RESULTS: Total net ingredient cost was €88,153,174 for claimants on PPI therapy during 2007. The estimated costing savings for each of the five scenarios in a one year period were: (i) €36,943,348 (42% reduction); (ii) €29,568,475 (34%); (iii) €21,289,322 (24%); (iv) €40,505,013 (46%); (v) €34,991,569 (40%). CONCLUSION: There are opportunities for substantial cost savings in relation to PPI prescribing if implementation of clinical guidelines in terms of generic substitution and step-down therapy is implemented on a national basis

Assemblages of conflict termination:popular culture, global politics and the end of wars

The question of how wars end is of continued importance, especially in the context of the ongoing War on Terror. This question has traditionally been approached within International Relations through rational choice theories, logical modelling and game theory. Such approaches have become increasingly ill-suited to capturing the complexity and ambiguity of contemporary warfare and the War on Terror in particular. These battlefield ambiguities are often at odds with political and public desires to see decisive victory in wars. This article builds on recent critical work within War Termination Studies in order to re-conceptualise the end of war as assemblages. By paying greater attention to the affects inculcated by political rhetoric surrounding war and utilising the concepts of affect and emergence, this article presents a novel approach to the study of contemporary war termination. Utilising popular culture, increasingly seen as a crucial site of global politics, the case study analysed here advances the argument that sacrifice emerges from cinema and presidential rhetoric as a trope that allows leaders to claim victory in war despite indecisive conditions of the ground. Through affective cinematic encounters, conceptualised here through the end of wars assemblages, audiences can become more accepting of such political claims

Charles Joseph La Trobe and his administration of the Wadawurrung, 1839‑1853

Maggie Black’s work as a writer has focused on disadvantaged people in Africa, Asia and Latin America. Her view of the damaging impact of contemporary forms of development on Indigenous societies is articulated in her book, International Development: Illusions and Realities (New Internationalist, 2015). This proved a useful basis for studying her great‑grandfather’s pioneering life in Victoria. Niel Black’s archive found its way to State Library Victoria thanks to Margaret Kiddle, author of Men of Yesterday (Melbourne University Press, 1961), which also drew heavily on his remarkable voice. This article is a shortened version of a chapter in the author’s Up Came a Squatter: Niel Black of Glenormiston 1839‑1880 (NewSouth, 2016)