'"These schemes will win for themselves the confidence of the people": Irish independence, poor law reform and hospital provision'

This article examines hospital provision in Ireland during the early twentieth century. It examines attempts by the newly independent Irish Free State to reform and de-stigmatise medical relief in former workhouse infirmaries. Such reforms were designed to move away from nineteenth century welfare regimes which were underpinned by principles of deterrence. The reform initiated in independent Ireland - the first attempted break-up of the New Poor Law in Great Britain or Ireland - was partly successful. Many of the newly named County and District Hospitals provided solely for medical cases and managed to dissociate such health care provision from the relief of poverty. However, some hospitals continued to act as multifunctional institutions and provided for various categories including the sick, the aged and infirm, 'unmarried mothers' and 'harmless lunatics'. Such institutions often remained associated with the relief of poverty. This article also examines patient fee-payment and outlines how fresh terms of entitlement and means-testing were established. Such developments were even more pronounced in voluntary hospitals where the majority of patients made a financial contribution to their treatment. The article argues that the ability to pay at times determined the type of provision, either voluntary or rate-aided, available to the sick. However, it concludes that the clinical condition of patients often determined whether they entered a more prestigious voluntary hospital or the former workhouse. Although this article concentrates on two Irish case studies, County Kerry and Cork City; it is conceptualised within wider developments with particular reference to the British context.

'The End of the Irish Poor Law?: Welfare and Healthcare Reform in Revolutionary and Independent Ireland'

This book explores welfare provision in Ireland from the revolutionary period to the 1940s, This work is a significant addition to the growing historiography of twentieth-century Ireland which moves beyond political history. It demonstrates that concepts of respectability, deservingness, and social class where central dynamics in Irish society and welfare practices. This book provides the first major study of local welfare practices, policies, and attitudes towards poverty and the poor in this era.

This book’s exploration of the poor law during revolutionary and independent Ireland provides fresh and original insights into this critical juncture in Irish history. It charts the transformation of the former workhouse system into a network of local authority welfare and healthcare institutions including county homes, county and hospital hospitals, and mother and baby homes. This book provides historical context to current day debates and controversies relating to the institutionalisation of unwed mothers and child welfare policies.

This book undertakes two cases studies on county Kerry and Cork city; also, Irish experiences are placed against the backdrop of wider transnational trends.

This work has multiple audiences and will appeal to those interested in Irish social, culture, economic and political history. This book will also appeal to historians of welfare, the poor law, and the social history of medicine. It also informs modern-day social affairs.

Use of SLAM and PVRL4 and Identification of Pro-HB-EGF as Cell Entry Receptors for Wild Type Phocine Distemper Virus

Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.

A Randomized Controlled Trial Evaluation of an After-School Pro-Social Behavior Program in an Area of Socioeconomic Disadvantage

A randomized controlled trial was used to evaluate the effects of a pro-social behavior after-school program called Mate-Tricks for nine and ten year old children and their parents living in an area of significant socioeconomic disadvantage. The children were randomly assigned to an intervention (n=220) or a control group (n=198). Children were compared on measures of pro-social behavior, anti-social behavior and related outcome measures. The trial found adverse effects on four outcomes among the intervention group compared to the control group: anti-social behavior increased on two different measures (d=+0.20) and (d=+0.18); child reported liberal parenting increased (d=+0.16); and child reported authoritarian parenting also increased (d=+0.20). In addition, parental participation was significantly associated with several program outcomes. It was concluded, that group based after-school behavior programs may have the potential to cause iatrogenic effects and must be designed, piloted, evaluated and implemented with a high degree of care.

Supplementary feeding increases Common Buzzard Buteo buteo productivity but only in poor-quality habitat

Temporal heterogeneity in the effects of food supply during the breeding season on the productivity of the Common Buzzard Buteo buteo was investigated in a supplementary feeding experiment. Pairs were fed artificially (1) before egg-laying, (2) after chicks hatched and (3) continuously throughout the season, and compared with (4) unfed controls. Pairs fed before egg-laying had marginally larger clutches than those not fed, but lay date, egg volume and weight, brood size and hatching success were unaffected. Territorial quality had far greater effects, with pairs nesting in low-quality habitats (bog, scrub and semi-natural grassland) laying later and having lower hatching success, smaller broods and fewer fledglings than those in more productive agricultural landscapes. Supplementary feeding after egg hatching neutralized the negative effect of poor habitat, resulting in fed birds having significantly more fledglings. This study emphasizes the importance of food availability when provisioning chicks in suboptimal habitats and has implications for the success of diversionary feeding in reducing game losses to Buzzards.

MIR-433 Predicts poor response to chemotherapy in ovarian cancer patients by the induction of cellular senescence

Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynaecological malignancy. Such mortality is predominantly associated with the development of an intrinsic and acquired resistance to chemotherapy, the lack of targeted therapies and the lack of biomarkers predicting response to standard treatment.

Our clinical data demonstrates that increased miR-433 expression in primary high grade serous OC (HGSOCs) is significantly associated with poor PFS (n=46, p=0.024). Interestingly, the IHC analysis of two miR-433 targets: MAD2 [1] and HDAC6 shows that low IHC levels of both proteins is also significantly associated with worse outcome (p=0.002 and 0.002 respectively; n=43). Additionally, the analysis of miR 433 in the publicly available TCGA dataset corroborates that high miR-433 is significantly correlated with worse OS for patients presenting with OC (n=558 and p=0.027). In vito, in a panel of OC cell lines, higher miR-433 and lower MAD2 and HDAC6 levels were associated with resistance to paclitaxel.

To further investigate the role of miR-433 in the cellular response to chemotherapy, we generated an OC cell line stably expressing miR-433 or miR-control. MTT viability assays and Western Blot analyses established that miR-433 cells were more resistant to paclitaxel treatment (50nM) compared to miR-controls. Importantly, we have shown for the first time that miR 433 induced senescence resulting in a chracteristic flattened morphology and down-regulation of phosphorylated Retinoblastoma (p Rb), a molecular marker of senescence. Surprisingly, miR 433 induced senescence was independent from two well recognised senescent drivers: namely p53/p21 and p16. To explore this further we performed an in silico analysis of seven microRNA platforms which indicated that miR 433 potentially targets Cyclin-dependent kinase CDK6, which promotes sustained phosphorylation of Rb and thus cell cycle progression. In vitro, the overexpression of pre-miR-433 resulted in diminished CDK6 expression demonstrating a novel interaction between miR-433 and CDK6.

In conclusion, this study demonstrates that high miR-433 expression predicts poor outcome in OC patients by putatively rendering OC cells resistant to paclitaxel treatment through the induction of cellular senescence identifying this microRNA as a potential marker of chemoresponse.

Pro-fragrant ionic liquids with stable hemiacetal motifs: water-triggered release of fragrances

Stable liquid and solid salts in the form of elusive hemiacetals, appended with fragrant alcohols, have been synthesised as pro-fragrances, and the controlled release of these fragrances, triggered by water, is demonstrated

A cross-sectional study demonstrating increased serum amyloid A-related inflammation in high density lipoproteins from subjects with type 1 diabetes mellitus and how this association was augmented by poor glycaemic control

Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins(HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this propertymay be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matchedcontrol subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-,and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly inserum (P = 0.088), and significantly in HDL2 (P  = 0.003) and HDL3 (P  = 0.005). When the T1DM group were separated accordingto mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared towhen HbA1c was <8.34% (P  < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAAincreased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P  > 0.05).This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poorglycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increasedatherosclerosis risk.

Does conurbation affect the risk of poor mental health? A population based record linkage study

To determine if urban residence is associated with an increased risk of anxiety/depression independent of psychosocial stressors, concentrated disadvantage or selective migration between urban and rural areas, this population wide record-linkage study utilised data on receipt of prescription medication linked to area level indicators of conurbation and disadvantage. An urban/rural gradient in anxiolytic and antidepressant use was evident that was independent of variation in population composition. This gradient was most pronounced amongst disadvantaged areas. Migration into increasingly urban areas increased the likelihood of medication. These results suggest increasing conurbation is deleterious to mental health, especially amongst residents of deprived areas