The Wicked Machinery of Government: Malta and the Problems of Continuity under the New Model Administration

This is a study focused on the early years of British rule in Malta (1800-1813). It explores the application to the island of the “new model” of colonial government, one based on direct rule from London mediated by the continuation of existing laws and institutions. Systemic deficiencies are identified. These tended to undermine the effectiveness of direct British rule. This study also reveals, in the context of legal and constitutional continuity, unresolved tensions between modernity and tradition. The political stability of the island was damaged and the possibility of continued British possession was threatened

Child Health Care in Ireland

The Irish health care system is based on a complex and costly mix of private, statutory, and voluntary provisions. The majority of health care expenditure comes from the state, with a significant proportion of acute hospital care funded from private insurance, but there are relatively high out-of-pocket costs for most service users. There is free access to acute hospital care, but not for primary care, for all children. About 40% of the population have free access to primary care. Universal preventive public health services, including vaccination and immunization, newborn blood spot screening, and universal neonatal hearing screening are free. Major health challenges include poverty, obesity, drug and alcohol use, and mental health. The health care system has been dominated for the last 5 years by the impact of the current recession, which has led to very sharp cuts in health care expenditure. It is unclear if the necessary substantial reform of the system will happen. Government policy calls for a move toward a patient-centered, primary care-led system, but without very substantial transfers of resources and investment in Information and Communication Technology, this is unlikely to occur

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite's food vacuole and alter drug sensitivities

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction of the C101F or L272F mutation into a chloroquine-resistant variant of PfCRT reduced the ability of this protein to transport chloroquine by approximately 93 and 82%, respectively, when expressed in Xenopus oocytes. These data provide, at least in part, a mechanistic explanation for the increased sensitivity of the mutant parasite lines to chloroquine. Taken together, these findings provide new insights into PfCRT function and PfCRT-mediated drug resistance, as well as the food vacuole, which is an important target of many antimalarial drugs

Peer expectations about outstanding competencies of men and women medical students

Men and women enrolled in a combined premedical-medical school programme were asked as they began their clinical training to rate their anticipated competence on sixteen criteria relevant to medical practice. Competence dimensions tapped scientific/technical skills, dedication/commitment, and interpersonal skills. Students then were asked to nominate one classmate whom they expected might be‘the best’in each area. Self-ratings revealed few differences among men and women. Peer nominations, however, revealed a preponderance of male nominees in ten competence areas. Women dominated nominations only in the category of sensitivity to patients. Patterns persisted when peer nominations were controlled for students’academic standing and self-ratings on parallel dimensions. The data suggest that medical school peer groups share expectations about competencies of men and women as physicians which are consistent with generalized sex stereotypes and career patterns of men and women physicians.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74843/1/1467-9566.ep11340055.pd

Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity

Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide

\ua9 2022 The authors Published by Bioscientifica Ltd.Objective: Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design: A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods: Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results: There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions: DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy

Co-infection status of novel parvovirus’s (PPV2 to 4) with porcine circovirus 2 in porcine respiratory disease complex and porcine circovirus-associated disease from 1997 to 2012

Publication history: Accepted - 12 September 2020; Published online - 18 October 2020.As global pig health diseases, porcine respiratory disease complex (PRDC) and porcine circovirus-associated disease (PCVAD) generate substantial economic losses despite pigs been vaccinated against the primary causative virus, highlighting the importance of understanding virome interactions and specifically co-factor infections. Established primary endemic pathogens for PRDC include porcine circovirus 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSv) and swine influenza virus (SIV), and PCV2 aetiology in interaction with other co-infecting viruses can result in PCVAD. Porcine parvovirus (PPV) 1 is a well-characterized virus with an available vaccine preventing reproductive failure in sows. However, whilst novel PPV 2 to 7 viruses have been identified since 2001, their viral pathogenic potential in clinical and subclinical disease remains to be determined. Therefore, this study has sought to develop a better understanding of their potential role as associated co-infections in PRDC and PCVAD by examining archival samples for the presence of PCV2 and the novel parvoviruses PPV2-4 from clinically diseased pigs across production age stages. Epidemiologically, the novel PPV2 was found to be the most prevalent within the fattener age group with PPV2-4 statistically associated with pig respiratory disease and enteric ulcers. Additionally, statistical modelling by latent class analysis (LCA) on veterinary pathology scored pigs found a clustering co-factor association between PPV2 and PCV2, suggesting the novel PPV may be involved in PRDC and PCVAD. Phylogenetic analysis of novel PPVs revealed the PPV2 capsid evolution to be diverged from the original strains with a low nucleotide homology of 88%–96% between two distinct clades. These findings determine that novel PPV 2–4 viruses are statistically associated as co-infectors in a diseased pig population, and significantly detected PPV2 clustering co-infection frequency with PCV2 in PRDC and PCVAD diseased pigs through LCA analysis

The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways