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D-peptide hydrogels as a long-acting multipurpose drug delivery platform for combined contraception and HIV prevention
Get PDFNew multipurpose prevention technology products for use by women, focused on reducing HIV infection andpreventing unwanted pregnancies, are a global health priority. Discreet long-acting formulations will empowerwomen with greater choice around their sexual health. This paper outlines the development of a long-actingtechnology that enables multiple drugs to be incorporated within one injectable platform. This fixed-dosecombination product is formed from a phosphorylated D-peptide (naphthalene-2-ly)-acetyl-diphenylalaninelysine-tyrosine-glycine-OH (Napffky(p)G-OH) that enables the highly hydrophobic drugs MIV-150 (HIV antiretroviral) and etonogestrel (contraceptive) to be solubilized together within aqueous solvents. Upon subcutaneousinjection, this D-peptide-drug combination self-assembles in response to phosphatase enzymes present within theskin space to form an in situ forming drug-releasing hydrogel depot. Oscillatory rheology confirmed the formationof hydrogels, which began within ~10 s exposure to 3.98 U/mL phosphatase enzymes and continued for ~198mins for a Napffk(MIV-150)y(p)G-OH + Napffk(ENG)y(p)G-OH combination (8:2 ratio). Biostability againstproteases, an important consideration for long-acting injectables, was demonstrated for at least 28 days in vitro.Covalent attachment of each drug to the D-peptide via an ester linkage enabled sustained release of the drug in anunmodified form via hydrolysis of the D-peptide-drug linker. This significantly reduced the initial drug burst.Low toxicity was also demonstrated in vitro via cell culture (MTS, LHS, Live/Dead®) and within in vivo studies(H&E staining). The fixed dose combination was able to deliver clinically relevant concentrations of each drug toSprague–Dawley rats for at least 49 days, providing proof-of-concept for the use of hydrogel-forming D-peptides(Napffky(p)G-OH) as a long-acting injectable platform for the delivery of multiple hydrophobic drugs
Northern Ireland Childcare Strategy: A Work in Progress?
Get PDFNorthern Ireland has been without a Childcare Strategy for more than a decade – the only region in the United Kingdom (UK) that does not have one. As a devolved responsibility, progress in childcare has been significantly limited, and there is currently no government-funded childcare provision available. This is compared to England, Scotland, and Wales, where investment to expand provision has been introduced to help parents meet the cost of childcare by providing funded entitlement. This article examines and discusses policy developments in early education and childcare in Northern Ireland and the other UK nations. It is argued that the lack of progress by the Northern Ireland Executive to develop a Childcare Strategy overlooks it’s economic and social importance and reflects how childcare continues to be underfunded and undervalued
Experiences of medical students and doctors with dyslexia: a systematic review
Get PDFIntroductionDyslexia can be defined as a neurodevelopmental learning difficulty characterised by issues with phonological awareness, affecting performance and progression within medical education. There is a need to identify how to provide effective support for medical students and postgraduate doctors with dyslexia. The aim of this systematic review was to explore the experiences of, and identify strategies for, undergraduate medical students and postgraduate medical doctors with dyslexia within existing literature.MethodsA search strategy was undertaken on databases relevant to medical education. Included studies concerned either medical students or postgraduate medical doctors with dyslexia. A quality appraisal was undertaken and narrative synthesis employed to produce a final report.ResultsThirty-one articles were included in the final synthesis, with seven deemed high-risk of bias. Four overarching themes were identified. There are largely negative experiences, such as stigma, reported. Furthermore, dyslexia can impact assessment performance, with reasonable adjustments effective for written examinations. Moreover, strategies employed to reduce difficulties include peer support, organisational inclusivity and interactive educational methodologies. Additionally, dyslexia impacts the career trajectory of doctors.DiscussionTraining programmes should promote an inclusive environment through raised awareness and provision of reasonable adjustments. A range of potential strategies have been identified to improve the educational experiences of students with dyslexia, but these should be flexible according to individual needs. Further research is warranted within postgraduate medical training and experiences in the United States
Null subject comprehension and production revisited: a look at English and Italian
Get PDFThis study will investigate how children acquire the option to drop the subject of a sentence, or null subjects (e.g., "Tickles me" instead of "He tickles me"). In languages that do not permit null subjects, children produce sentences with null subjects from 1 to 3 years of age. This non-adultlike production has been explained by two main accounts: first, the null subject sentences may accurately reflect the children's linguistic knowledge, that is, a competence account. Alternatively, they may result from immature processing resources, therefore underestimating children's competence, that is, a performance account. We will test the predictions of these accounts by using a central fixation preference procedure and elicited imitation to measure children's comprehension and production, respectively, in monolingual 19- to 28-month-olds acquiring English (a non-null subject language) and Italian (a null subject language). The results will shed light on acquisition across languages, and the features that provide evidence to a learner
MDAG-Net: Multi-Domain Association-Guided Network for Image-based Long-term Visual Localization
Get PDFIn the case of long-term changing environment, long-term visual localization is a challenging problem in autonomous driving and mobile robots. Due to the influence of season, illumination and other changing weather conditions, the traditional image retrieval methods are difficult to achieve ideal results in long-term visual localization. Therefore, inspired by the human brain associative recognition function, an image retrieval based on a multidomain association-guided network is proposed to solve the long-term visual localization problem. The key idea is to extract the discriminative domain-invariant features in different scenes through multidomain image transformation of the perceptual network and the conceptual network. In addition, in order to better associate image features of different scenes in the conceptual network and guide the perceptual network to obtain more robust domain invariant features, an association-guided module is designed without the need for external datasets. On this basis, the domain feature loss function and the guidance mechanism of the loss function are introduced to assist these two network models training to obtain better performance. Finally, experiments are carried out on the CMU-Seasons dataset and the RobotCar-Seasons dataset. Compared with some state-of-the-art methods, the proposed method improved the high-precision localization result of urban, suburban, and park scenes in the CMU-Seasons dataset by 1.5%, 0.5%, and 0.7%, respectively, which also can verify the effectiveness of the proposed method under various seasonal and illumination conditions.</p
Developing leadership and resilience through early access master’s education for newly graduated, adult nurses::a cross-sectional survey.
Get PDFAim: To explore the impact of an early access master’s experiential programme on leadership skills and resilience in new graduate nurses.Background: Succession planning for nursing, requires leadership and resilience development in new nurses. Literature suggests that early access to master’s education can produce nurses with the necessary skills.Design: A comparative, cross-sectional survey design.Methodology: A survey using the NHS Leadership Framework Self-Assessment Tool (2012) and Connor-Davidson Resilience Scale 25 (2003) was distributed in September 2021, to graduates, two years, post-registration, from an Adult Nursing programme. Self-assessed scores of graduates enrolled directly onto a non-specialist, master’sinitiative were compared with those who did not undertake the initiative.Results: Findings showed significant correlation between leadership and resilience scores. Master’s participants scored themselves more strongly in six of seven Leadership Domains and four of five resilience factors than those not enrolled on the master’s, with a difference in the overall mean CD-RISC-25 score of 81.69 for master’s graduates, compared with 70.84. Qualitative analysis of examples of additional leadership responsibilities included being in charge, training newer staff and maintaining patient and staff safety.Conclusion: This study has shown that master’s education, early in graduate nurses’ careers, develops leadership skills and resilience required for new nurse leaders. Investment is needed, therefore, in educational opportunities for these new graduates to enable leadership and resilience development and in creating supportive environments allowing the use of this learning to lead change and influence care delivery. This should have a positive impact on patient outcomes, job satisfaction and aid retention
Exploring Developmental Outcomes for Children Attending Community-based Pre-Schools in the Ermera and Viqueque Municipalities of Timor-Leste
Get PDFThere is a substantial body of evidence which indicates that early childhood programmes have a positive effect on children's school readiness, academic achievement, and social and emotional development. Indeed, these benefits can last into adulthood. Based on this evidence base, many countries that strive to build their early childhood education offer to enhance later chances of prosperity. LINKS is an NIHR-funded study, carried out by a team from Queen's University Belfast and Ulster University, with support from UNICEF. The project aims to explore the impact of early childhood development programmes on social cohesion/peacebuilding in six conflict-affected low- and middle-income countries (LMICs); Timor-Leste, Viet Nam, Mali, Egypt, Kyrgyzstan and Tajikistan. This paper will focus on research carried out as part of the LINKS study in Timor-Leste which aimed to evaluate the impact of UNICEF community-based alternative pre-schools (CBAPs) in Timor-Leste. This research, carried out in 2020, employed a quasi-experimental pre- post-test design with a public pre-school control group. A total of 607 children were recruited to participate from 33 pre-schools: 508 completed post-tests after nine months of pre-school exposure to the CBAP programme. The East-Asia Pacific Early Childhood Development Scales (EAP-ECDS) were used to assess the development of children in the current study. Results of the post-test suggest that despite differences in time children spend in pre-school and infrastructure between the school types, attendance at CBAPs appears to close the developmental gap seen at the pre-test (baseline) between children in the two groups. The findings underline the importance of pre-school access and early learning experiences to the development of children at the highest risk of not reaching their developmental potential. The results point to the need to scale the intervention and to carry out an experimental effectiveness evaluation of this promising programme
Marginal marine spring carbonates defining an emergent rocky shoreline at Cape Freycinet, Western Australia
Get PDFModern and Holocene tufa microbialites have been documented globally on groundwater spring-fed supratidal rock coasts. Here, we document the first emergent facies assemblage and demonstrate its utility as a palaeo-shoreline (and sea-level) indicator. At Cape Freycinet, Western Australia, discrete palaeo-spring-associated deposits comprise five distinct facies that collectively define a Quaternary shoreline on a granitic rock coast similar to the contemporary coast. A palaeosol facies, passes laterally seaward into tufa microbialite on sub-horizontal bedrock, associated with oncoids. The most seaward facies is a microbially-cemented sand representing deposition in the upper-intertidal to supratidal zone of a sandy embayed beach, flanked by prominent headlands. A tufa-lithoclast breccia indicates occasional high-energy events. Facies distributions are controlled by bedrock topography in relation to palaeo-sea-level and the distinct suite of marginal marine, springline-associated facies define a Quaternary palaeo-shoreline at ca. +13 m above sea-level. The approach demonstrates the utility of marginal marine microbialite and related carbonate deposits as indicators of Quaternary sea-level on rock coasts
Antiretroviral drug exposure in pregnancy and risk of congenital anomalies: a European case/non-case malformed study
Get PDFPurposeAntiretroviral drugs are recommended during pregnancy to achieve HIV viral suppression and reduce mother-to-child transmission. Congenital anomaly signals were reported after fetal exposure to antiretroviral drugs in several studies warranting further investigation. We aimed to evaluate the risk of congenital anomalies after fetal exposure to antiretroviral drugs using the European congenital anomaly registry data.MethodsA case/non-case study was performed, using the EUROmediCAT central database. All the congenital anomalies, exposed to any antiretroviral drugs, were included from 1995 to 2019. We explored each signal identified from the literature for associations between congenital anomalies and specific antiretroviral exposures. We compared antiretroviral exposure between the signal anomalies (cases) and all other malformed registrations (controls). Reporting odds ratio (ROR) and their 95% confidence intervals were estimated and adjusted for registry and maternal age.ResultsBetween 1995 and 2019, 173 cases of congenital anomalies were observed after any exposure to antiretroviral drugs. The signal previously identified in the literature between congenital heart defects and exposure to zidovudine was confirmed in the main analysis (aROR 3.66 [1.63–8.23]). Other signals identified in the literature were not confirmed, although two cases of hypospadias and two cases of limb defects were reported after zidovudine and atazanavir exposure, respectively. The signal detection analysis did not reveal any new signal after applying the Bonferroni correction.ConclusionsOur study does not reveal new signals but confirms the previously identified signal between congenital heart defects and fetal exposure to zidovudine. The physio-pathological hypothesis induced by zidovudine exposure should be explored in future studies
M.N. Pokrovskii and the Origins of Soviet Historiography
Get PDFBook Review (M.N. Pokrovskii and the Origins of Soviet HistoriographyJames D. White, Leiden, Brill, 2024, 332 pp., €129 (hardback), ISBN: 9789004703872