The National and International Implications of a Decade of Doctor Migration in the Irish Context

Background: Between 2000 and 2010, Ireland became increasingly dependent on foreign-trained doctors to staff its health system. An inability to train and retain sufficient doctors to meet demand is the primary reason for the dependence on foreign-trained doctors. By 2008 the proportion of foreign-trained doctors was the second highest in the OECD. This increased dependence on international medical migration has both national and international policy implications. Methods: Registration data were obtained from the Medical Council of Ireland (MCI) for a ten year period: 2000-2010. Data indicate country of qualification but not nationality. The total number of registrants and entrants (n) was determined for each year. Immigration data were also obtained on the number of work visas issued to doctors. Registration and visa data were then compared in order to estimate doctor migration to Ireland 2000-2010. Results: The proportion of foreign-trained doctors rose from 13.4% of all registered doctors in 2000 to 33.4% by 2010. The largest increase was in foreign-trained doctors from outside the EU, rising from 972 (7.4%) in 2000 to 4,740 (25.3%) of registered doctors in 2010. The biggest source country in 2000 was Pakistan. By 2010, South Africa had become the biggest source country. The number of foreign-trained doctors from other EU countries doubled from 780 in 2000 to 1,521 in 2010. Conclusions: Registration data are likely to over-estimate and visa data under-estimate the numbers of doctors actively working in Ireland. However, they serve to illustrate Ireland’s rapidly increasing and potentially unsustainable reliance on foreign-trained doctors; and to highlight the need for better data to measure migratory flows. Improved measurement of health worker migration is necessary both for national workforce planning and to fulfil the requirements of the WHO Global Code on the International Recruitment of Health Personnel

Autophagy is Required for mTOR-Mediated Anabolism in Skeletal Muscle

PURPOSE: While much has been discovered about the role autophagy in protein degradation, recent evidence suggests that autophagy is required for muscular adaptations to exercise, hinting at a hitherto unknown cross-talk between autophagic proteolysis and muscle protein anabolism. Here, we set out to further elucidate the metabolic mechanisms by which autophagy may influence protein anabolism. METHODS: L6 myoblasts received either electrical pulse stimulation (EPS) to induce muscle contraction or were unstimulated to serve as controls, and were then treated with an inhibitor of the ATG4 enzyme which catalyzes the initial step of autophagy NSC185058 (NSC, 100 μM) or DMSO as a vehicle control (VC). After 24 hours, cells were lysed and Western immunoblotted for P70S6K, DEPTOR, MAPK, AMPK, LC3, and P62. Differences between VC and NSC treated groups were assessed by a two-tailed t-test, while comparisons between VC, EPS, and EPS+NSC groups were made using one-way ANOVA and SNK post-hoc test, with α levels set at 0.05. RESULTS: EPS induced a 97% increase in P70S6K phosphorylation (p\u3c0.05), with NSC treatment blunting this effect, leading to a 22% increase (P\u3e0.05). EPS resulted in a 37% reduction in DEPTOR content (p\u3c0.05); however, NSC treatment alone produced a 166% decrease in DEPTOR level (p\u3c0.05), with EPS+NSC leading to an even larger reduction (-766%) in DEPTOR than EPS alone. NSC treatment led to a decrease (-85%, p\u3e0.05) LC3II/I ratio relative to VC, which was reduced in both the EPS (-68%, p\u3c0.05) and EPS+NSC (-87%, p\u3c0.05) conditions. P62 content increased by 749% with EPS (p\u3c0.05), with no significant difference in P62 level between VC and EPS+NSC, and NSC treatment alone led to a 61% decrease in P62 (p\u3c0.05). MAPK phosphorylation was elevated in both EPS (99.9%, p\u3e0.05) and EPS+NSC (149.13, p\u3c0.05). Neither NSC nor EPS+NSC altered phosphorylation status of AMPK. CONCLUSION: Despite reductions in DEPTOR, mTOR activity was blunted in EPS+NSC cells, indicating that mTOR mediated anabolic signaling requires autophagy post muscle contraction. This is particular to the mTOR pathway, as an increase in MAPK phosphorylation was still observed in EPS+NSC. While the decrease in LC3II/I ratio and accumulation of P62 seen after EPS are likely due to inhibition of autophagy due to mTOR activity, our data indicate that inhibition of ATG4 by NSC185058 blunts mTOR activity after muscle contraction. This effect is not due to activation of the cellular energy sensor AMPK, as we found no increase in AMPK phosphorylation in any condition. Further work will be required to fully elucidate the mechanism by which NSC185058 inhibits mTOR-mediated anabolism

The βI domain promotes active β1 integrin clustering into mature adhesion sites

Modulation of integrin function is required in many physiological and pathological settings, such as angiogenesis and cancer. Integrin allosteric changes, clustering, and trafficking cooperate to regulate cell adhesion and motility on extracellular matrix proteins via mechanisms that are partly defined. By exploiting four monoclonal antibodies recognizing distinct conformational epitopes, we show that in endothelial cells (ECs), the extracellular βI domain, but not the hybrid or I-EGF2 domain of active β1 integrins, promotes their FAK-regulated clustering into tensin 1–containing fibrillar adhesions and impairs their endocytosis. In this regard, the βI domain–dependent clustering of active β1 integrins is necessary to favor fibronectin-elicited directional EC motility, which cannot be effectively promoted by β1 integrin conformational activation alone

An individual based computational model of intestinal crypt fission and its application to predicting unrestrictive growth of the intestinal epithelium.

Intestinal crypt fission is a homeostatic phenomenon, observable in healthy adult mucosa, but which also plays a pathological role as the main mode of growth of some intestinal polyps. Building on our previous individual based model for the small intestinal crypt and on in vitro cultured intestinal organoids, we here model crypt fission as a budding process based on fluid mechanics at the individual cell level and extrapolated predictions for growth of the intestinal epithelium. Budding was always observed in regions of organoids with abundant Paneth cells. Our data support a model in which buds are biomechanically initiated by single stem cells surrounded by Paneth cells which exhibit greater resistance to viscoelastic deformation, a hypothesis supported by atomic force measurements of single cells. Time intervals between consecutive budding events, as simulated by the model and observed in vitro, were 2.84 and 2.62 days, respectively. Predicted cell dynamics was unaffected within the original crypt which retained its full capability of providing cells to the epithelium throughout fission. Mitotic pressure in simulated primary crypts forced upward migration of buds, which simultaneously grew into new protruding crypts at a rate equal to 1.03 days-1 in simulations and 0.99 days-1 in cultured organoids. Simulated crypts reached their final size in 4.6 days, and required 40 6.2 days to migrate to the top of the primary crypt. The growth of the secondary crypt is independent of its migration along the original crypt. Assuming unrestricted crypt fission and multiple budding events, a maximal growth rate of the intestinal epithelium of 0.10 days-1 43 is predicted and thus approximately 22 days are required for a 10-fold increase of polyp size. These predictions are in agreement with the time reported to develop macroscopic adenomas in mice after loss of Apc in intestinal stem cells

DiSSCo Prepare WP7 –D7.3 Assessment tools and direction map to the implementation of common DiSSCo policies

The Distributed System for Scientific Collections (DiSSCo) Research Infrastructure will operate a number of e-services, all of which will have policy requirements for participating institutions. These policies include those related to digital and physical access to specimens, digital image and specimen metadata, and FAIR / Open Data. Previous projects have shown that the policy landscape is complex, and Task 7.3 has developed a policy self-assessment tool that will allow DiSSCo to assess policy alignment across the consortium. This deliverable describes the development of the policy self-assessment tool and provides a walkthrough of the key features. The same technical framework was used to create a digital maturity tool, which was initially proposed by Task 3.1, and this is also described within this document. A set of recommendations are included that outline the future direction for the development of the policy tool.The Distributed System for Scientific Collections (DiSSCo) Research Infrastructure will operate a number´of e-services, all of which will have policy requirements for participating institutions. These policies include those related to digital and physical access to specimens, digital image and specimen metadata, and FAIR / Open Data. Previous projects have shown that the policy landscape is complex, and Task 7.3 has developed a policy self-assessment tool that will allow DiSSCo to assess policy alignment across the consortium. This deliverable describes the development of the policy self-assessment tool and provides a walkthrough of the key features. The same technical framework was used to create a digital maturity tool, which was initially proposed by Task 3.1, and this is also described within this document. A set of recommendations are included that outline the future direction for the development of the policy tool

ETN Valued Species and Sites Report

Provide operations and maintenance support to scientific teams initiating studies of valued species, such as Bluefin tuna, European eel, sea bass, sea trout. To achieve this deliverable a workshop will be hold focussing on launching and networking activities

The CC-Bio Project: Studying the Effects of Climate Change on Quebec Biodiversity

Anticipating the effects of climate change on biodiversity is now critical for managing wild species and ecosystems. Climate change is a global driver and thus affects biodiversity globally. However, land-use planners and natural resource managers need regional or even local predictions. This provides scientists with formidable challenges given the poor documentation of biodiversity and its complex relationships with climate. We are approaching this problem in Quebec, Canada, through the CC-Bio Project (http://cc‑bio.uqar.ca/), using a boundary organization as a catalyst for team work involving climate modelers, biologists, naturalists, and biodiversity managers. In this paper we present the CC-Bio Project and its general approach, some preliminary results, the emerging hypothesis of the northern biodiversity paradox (a potential increase of biodiversity in northern ecosystems due to climate change), and an early assessment of the conservation implications generated by our team work