The Outlook for Credit in the Irish Economy

This note presents estimates of the likely credit requirements of different sectors of the economy over a short-term horizon to 2013. The measure of credit “demand” used in the analysis is the stock of outstanding loans to the Irish private sector from the resident banking sector. The results indicate a substantial fall in the amount of loans outstanding by 2013, the bulk of which is contained within Property (construction and real estate) and Personal Mortgage lending. Despite the projected fall in the amount of outstanding credit allocated to Mortgage lending, as a sector it is expected to continue to account for the majority of outstanding loans to the Irish private sector.

Model-robust and model-sensitive designs.

Abstract: The main drawback of the optimal design approach is that it assumes the statistical model is known. In this paper, a new approach to reduce the dependency on the assumed model is proposed. The approach takes into account the model uncertainty by incorporating the bias in the design criterion and the ability to test for lack-of-fit. Several new designs are derived in the paper and they are compared to the alternatives available from the literature.A-optimality; Bias; D-optimality; Lack-of-fit; Model-discrimination; Model-robustness;

Elastic biodegradable starch/ethylene-co-vinyl alcohol fibre-mesh scaffolds for tissue engineering applications

The fabrication of a biomaterial scaffold, with adequate physical and structural properties for tissue engineering applications, is reported. A blend of starch with ethylene-vinyl alcohol (50/50 w/w, SEVA-C) is used to produce 3D fibre-mesh scaffolds by wet-spinning. The scaffolds are characterized in terms of morphology, porosity, interconnectivity, and pore size, using scanning electron microscopy (SEM) and microcomputed tomography (μCT). The degradation behavior, as well as the mechanical properties of the scaffolds, is investigated in presence of alpha-amylase enzyme at physiological concentration. Scaffolds with porosities ranging from 43 to 52%, interconnectivity of ∼70.5% and pore size between 118 and 159 μm, can be fabricated using the proposed methodology. The scaffolds exhibit an elastic behavior in the wet state with a compressive modulus of 7.96±0.32 MPa. Degradation studies show that SEVA-C scaffolds are susceptible to enzymatic degradation by alpha-amylase, confirmed by the increase of weight loss (40% of weight loss after 12 weeks) and presence of degradation products (reducing sugars) in solution. The diameter of SEVA-C scaffolds decreases with degradation time, increasing the overall porosity, interconnectivity and pore size. In vitro cell studies with human osteosarcoma cell line (SaOs-2) showed a nontoxic and cytocompatible behavior of the developed fibre mesh scaffolds. The positive cellular response, together with structural and degradable properties, suggests that 3D SEVA-C fibre-meshes may be good candidates as tissue engineering scaffolds. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40504. Copyright © 2014 Wiley Periodicals, Inc.This work was supported by national funds through the Portuguese Foundation for Science and Technology under the scope of the project PTDC/CTM/67560/2006 and by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme “COMPETE” (FCOMP-01-0124-FEDER-007148)

PP2A inhibition overcomes acquired resistance to HER2 targeted therapy

Background: HER2 targeted therapies including trastuzumab and more recently lapatinib have significantly improved the prognosis for HER2 positive breast cancer patients. However, resistance to these agents is a significant clinical problem. Although several mechanisms have been proposed for resistance to trastuzumab, the mechanisms of lapatinib resistance remain largely unknown. In this study we generated new models of acquired resistance to HER2 targeted therapy and investigated mechanisms of resistance using phospho-proteomic profiling. Results: Long-term continuous exposure of SKBR3 cells to low dose lapatinib established a cell line, SKBR3-L, which is resistant to both lapatinib and trastuzumab. Phospho-proteomic profiling and immunoblotting revealed significant alterations in phospho-proteins involved in key signaling pathways and molecular events. In particular, phosphorylation of eukaryotic elongation factor 2 (eEF2), which inactivates eEF2, was significantly decreased in SKBR3-L cells compared to the parental SKBR3 cells. SKBR3-L cells exhibited significantly increased activity of protein phosphatase 2A (PP2A), a phosphatase that dephosphorylates eEF2. SKBR3-L cells showed increased sensitivity to PP2A inhibition, with okadaic acid, compared to SKBR3 cells. PP2A inhibition significantly enhanced response to lapatinib in both the SKBR3 and SKBR3-L cells. Furthermore, treatment of SKBR3 parental cells with the PP2A activator, FTY720, decreased sensitivity to lapatinib. The alteration in eEF2 phosphorylation, PP2A activity and sensitivity to okadaic acid were also observed in a second HER2 positive cell line model of acquired lapatinib resistance, HCC1954-L. Conclusions: Our data suggests that decreased eEF2 phosphorylation, mediated by increased PP2A activity, contributes to resistance to HER2 inhibition and may provide novel targets for therapeutic intervention in HER2 positive breast cancer which is resistant to HER2 targeted therapies

Evaluation of diffusion-weighted MRI and (18F) fluorothymidine-PET biomarkers for early response assessment in patients with operable non-small cell lung cancer treated with neoadjuvant chemotherapy

Objective: To correlate changes in the apparent diffusion coefficient (ADC) from diffusion-weighted (DW)-MRI and standardised uptake value (SUV) from fluorothymidine (18FLT)-PET/CT with histopathological estimates of response in patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy and track longitudinal changes in these biomarkers in a multicentre, multivendor setting. Methods: 14 patients with operable NSCLC recruited to a prospective, multicentre imaging trial (EORTC-1217) were treated with platinum-based neoadjuvant chemotherapy. 13 patients had DW-MRI and FLT-PET/CT at baseline (10 had both), 12 were re-imaged at Day 14 (eight dual-modality) and nine after completing chemotherapy, immediately before surgery (six dual-modality). Surgical specimens (haematoxylin-eosin and Ki67 stained) estimated the percentage of residual viable tumour/necrosis and proliferation index. Results: Despite the small numbers,significant findings were possible. ADCmedian increased (p 30% reduction in unidimensional measurement pre-surgery), showed an increase at Day 14 in ADC75th centile and reduction in total lesion proliferation (SUVmean x proliferative volume) greater than established measurement variability. Change in imaging biomarkers did not correlate with histological response (residual viable tumour, necrosis). Conclusion: Changes in ADC and FLT-SUV following neoadjuvant chemotherapy in NSCLC were measurable by Day 14 and preceded changes in unidimensional size but did not correlate with histopathological response. However, the magnitude of the changes and their utility in predicting (non-) response (tumour size/clinical outcome) remains to be established. Advances in knowledge: During treatment, ADC increase precedes size reductions, but does not reflect histopathological necrosis

Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria.

Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.)

Monitoring changes in submarine canyon coral habitats - Leg 1 (MoCha_SCan)

This survey focused on the maiden deployment of a number of novel, ROV-adapted lander systems in the Porcupine Bank Canyon (PBC) coral habitats, NE Atlantic. Cold water corals (CWCs) flourish on the Irish-Atlantic margin between 600 and 100 m water depth, where they form a number of structural habitat types (coral reefs, mounds and gardens). Recent research shows that deep water habitats, including CWC habitats on the Irish margin, may be impacted by recent environmental change. The main objectives of this survey are: a) to deploy 8 new lander systems within a range of coral habitats throughout the PBC; b) to complete mapping coverage within the PBC; c) to sample the coral, sediment and ambient watermass around the lander sites and; d) to sample particulate organic matter around key coral habitats. Data recorded via landers from each habitat will allow to determine the controls on habitat variability. Furthermore, this data can be used as a baseline to which later deployments at this site will be used to compare against. Completed canyon coverage will feed into a number of multiscale mapping projects including the H2020 project â Integrated Assessment of Atlantic Marine Ecosystems in Space & Timeâ (iATLANTIC) and the SFI-, GSI- and MI-funded â Mapping, Modelling and Monitoring Key Processes and Controls on Cold Water Coral Habitats in Submarine Canyonsâ (MMMonKey_Pro) programme. Video data will be used to characterise key coral habitat within the canyon and subsequesntly, HD DEMâ s will be generated as a central dataset for the multiscale projects listed above

The importance of communication and involvementin decision-making: A study in Ireland exploring birthsatisfaction using the Birth Satisfaction Scale-Revised (BSS-R)

Introduction:Evaluation in healthcare services has become a priority, globally1. The Government of Ireland has highlighted the importance of stakeholder engagement to identify the needs of women in the design and delivery of high-quality health services, driven by necessity rather than financial ability2. The Birth Satisfaction Scale-Revised (BSS-R), an internationally validated tool, and recommended for measuring childbirth satisfaction by the International Consortium for Health Outcomes Measurement (ICHOM)3; however, it has yet to be considered in the Irish context. The aim of the study was to explore birth satisfaction with a sample of new mothers in Ireland.Methods:A mixed-methods study was conducted including a survey that involved collection of data from the BSS-R 10-item questionnaire from 307 mothers over an 8-week period in 2019, in one urban maternity hospital in Ireland. Quantitative and qualitative data were collected. Qualitative data from the free-text comments of the survey questions were analyzed using content analysis.Results:Overall, women reported positive relationships with their care providers and were satisfied with the communication and support they received, as well as high levels of control and choice. Postnatal care, however, was highlighted as being less satisfactory with staffing levels described as inadequate.Conclusions:Understanding women’s birth experiences and what is important to them could facilitate midwives and other health professionals to improve the quality of their care and develop guidelines and policies that focus on women and their families’ needs. The vast majority of women rated their birthing experience as extremely positive. The main elements of care that contributed to a positive birthing experience for women were quality relationships with clinicians, choice and control, and emotional safety

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 (COVID-19) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy