NUI Maynooth Eprint Archive
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A critical appraisal of Friends of the Irish Environment v Government of Ireland
No full textThis case note examines the judgement of the Irish Supreme Court quashing Ireland’s National Mitigation Plan and the earlier judgement of the High Court dismissing judicial review proceedings in Friends of the Irish Environment v Government of Ireland. It explores the contrasting legal reasoning of the two courts on the issues of standard of review, justiciability, compliance of the National Mitigation Plan with the Climate Action and Low Carbon Development Act 2015, locus standi and the constitutionality and compatibility of the National Mitigation Plan with the European Convention on Human Rights
Book Review: Lydia Bracken, Same-Sex Parenting and the Best Interests Principle. Cambridge University Press, Cambridge, 2020
No full textHigh-throughput and high-sensitivity N-Glycan profiling: A platform for biopharmaceutical development and disease biomarker discovery
No full textProtein glycosylation contributes to critical biological function of glycoproteins. Glycan analysis is essential for
the production of biopharmaceuticals as well as for the identification of disease biomarkers. However, glycans
are highly heterogeneous, which has considerably hampered the progress of glycomics. Here, we present an
improved 96-well plate format platform for streamlined glycan profiling that takes advantage of rapid glycoprotein denaturation, deglycosylation, fluorescent derivatization, and on-matrix glycan clean-up. This approach
offers high sensitivity with consistent identification and quantification of diverse N-glycans across multiple
samples on a high-throughput scale. We demonstrate its capability for N-glycan profiling of glycoproteins from
various sources, including two recombinant monoclonal antibodies produced from Chinese Hamster Ovary cells,
EG2-hFc and rituximab, polyclonal antibodies purified from human serum, and total glycoproteins from human
serum. Combined with the complementary information obtained by sequential digestion from exoglycosidase
arrays, this approach allows the detection and identification of multiple N-glycans in these complex biological samples. The reagents, workflow, and Hydrophilic interaction liquid chromatography with fluorescence detection (HILIC-FLD), are simple enough to be implemented into a straightforward user-friendly setup. This improved
technology provides a powerful tool in support of rapid advancement of glycan analysis for biopharmaceutical
development and biomarker discovery for clinical disease diagnosis
The incredible years parenting program for foster carers and biological parents of children in foster care: A mixed methods study
No full textTrauma-related social, emotional and behavioral difficulties (SEBD) are common among children in foster care and are the primary reason for placement breakdown. SEBD in foster children – and especially in the context of unstable and troubled relationships with both foster and biological parents - affects the child’s future functioning and has substantial cost implications in terms of public service utilization. The aim of this study was to assess the utility and perceived effectiveness of the 18-week Incredible Years parenting program (IYPP) which was delivered, on an exploratory basis, to both biological and foster parents (including kinship and non-relative care) of 23 foster children (aged 3–10 years). Biological and foster parent pairs (n = 46) were assessed at pre-intervention and at 6-month follow up, using measures of child SEBD, parenting stress, competencies, and quality of child-parent/carer relationships. One-to-one interviews and a focus group were also undertaken with a subset of biological parents (n = 12), foster carers (n = 11) and Social Work clinicians (n = 5) who delivered the program; the findings were analyzed using grounded theory. Both biological and foster parents reported statistically significant improvements in child SEBD, parent–child relationships, and in parenting stress and competencies. The qualitative findings highlighted further benefits for families, such as an increased number of access visits between biological parents and children and improved relationships with Social Work clinicians. Several factors were identified as important when implementing the IYPP with foster children, including: potential difficulties in engaging both foster and biological parents within the Social Work infrastructure; making appropriate adaptations to program principles, and integrating delivery with a trauma-informed approach. These findings contribute to the growing body of evidence that the IYPP could add value to the standard training and supports for foster parents, children and biological parents
Individualised Funding: A Realist Analysis to Identify the Causal Factors That Facilitate Positive Outcomes
No full text: There is growing interest, internationally, in empowering people with disabilities, and the
United Nations have identified individualised funding as one way in which empowerment might
be achieved. ‘Individualised funding’ is an umbrella term for various publicly funded support
structures that provide personalised and individualised support services for people with a disability.
These aim to facilitate self-direction, empowerment, independence, and self-determination. The
findings of a recent mixed-methods systematic review of studies undertaken during an approximate
25-year period suggest positive effects with respect to quality of life, client satisfaction, and safety,
as well as very few adverse effects, although the evidence on cost-effectiveness was inconclusive.
This paper involved a re-examination of the qualitative findings of that review by employing a
realist framework to explore the interplay between key contexts and mechanisms, and how these
facilitate or inhibit positive outcomes associated with individualised funding and its underlying
programme theor
A Family-Focused Intervention for Parental Mental Illness: A Practitioner Perspective
No full textBackground: Parental mental illness (PMI) is common and can lead to children developing mental disorders. Family Talk (FT) is a well-known and widely implemented intervention designed to reduce the risk of transgenerational psychopathology. However, given the research to practise “gap,” very little qualitative research, to date, has
investigated practitioner experiences in implementing FT. This study aimed to explore the practitioner-perceived barriers and facilitators to the implementation and sustainability of FT within mainstream mental health settings.
Methods: This qualitative study was nested within a randomised controlled trial (RCT) of Family Talk [N = 86 families (139 parents, 221 children)] within 15 adult
(AMHS), child (CAMHS), primary care mental health, and child protection sites in Ireland. Semi-structured interviews and focus groups were undertaken with a purposive sample
of clinicians (n = 31) and managers (n = 10), based on their experiences of implementing FT. Interview data were transcribed verbatim, analysed using constructivist grounded
theory, and informed by Fixsen’s implementation science framework.
Results: Service providers highlighted a number of benefits for approximately two thirds of families across different diagnoses and mental health settings (AMHS/CAMHS/primary
care). Sites varied in their capacity to embed FT, with key enablers identified as acquiring managerial and organisational support, building clinician skill, and establishing interagency collaboration. Implementation challenges included: recruitment difficulties,
stresses in working with multiply-disadvantaged families, disruption in delivery due to the COVID-19 global pandemic, and sustainability concerns (e.g., perceived fit of FT with
organisational remit/capacity, systemic and cultural barriers to change).
Conclusion: This study is only the second qualitative study ever conducted to explore practitioner experiences in implementing FT, and the first conducted within the context
of an RCT and national research programme to introduce family-focused practise (FFP) for families living with PMI. The findings illuminate the successes and complexities of
implementing FFP in a country without a “think family” infrastructure, whilst highlighting a number of important generalisable lessons for the implementation of FT, and other similar interventions, elsewhere
Self-reported outcomes and patterns of service engagement after an acquired brain injury: a long-term follow-up study
No full textPrimary Objective: To describe the clinical characteristics, self-reported outcomes in domains relating to
activities of daily living and patterns of service engagement in the survivors of a moderate-to-severe
acquired brain injury over seven years.
Research Design: A longitudinal research design was used.
Methods and Procedures: Thirty-two individuals who sustained a moderate-to-severe acquired brain
injury completed a Sociodemographic and Support Questionnaire at one (t1) and seven years (t2) after
completing a publicly funded inpatient neurorehabilitation program.
Main Outcomes and Results: There were minimal changes in independent living, mobility, ability to
maintain key relationships and in return to work in the interval between t1 and t2. Sixty-nine percent of
participants engaged with two or more allied health professional services and 75% engaged with support
services in the community over the seven years.
Conclusions: There were minimal additional gains in outcomes relating to activities of daily-living and
there was a high level of service need in the first decade postinjury. Young and middle-aged individuals
who sustain an ABI may continue to live in the community for decades with some level of disability and
may require ongoing access to service
N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny
No full textTriple negative breast cancer (TNBC) has poor clinical outcomes and limited treatment options.
Chemotherapy, while killing some cancer cells, can result in therapeutic-induced-senescent (TIS) cells.
Senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Recently,
N- and O-linked glycosylation alterations have been associated with senescence. We aimed to profile
the N-linked glycans of whole cells, membrane, cytoplasm and EVs harvested from TIS TNBC cells and
to compare these to results from non-senescent cells. TIS was induced in the Cal51 TNBC cells using
the chemotherapeutic agent paclitaxel (PTX). Ultra-performance liquid chromatography (UPLC) analysis
of exoglycosidase digested N-linked glycans was carried out on TIS compared to non-treated control
cells. LC-Mass spectrometry (MS) analysis of the N-linked glycans and lectin blotting of samples was
carried out to confirm the UPLC results. Significant differences were found in the N-glycan profile of the
Cal51 membrane, cytoplasm and EV progeny of TIS compared to non-senescent cells. Protein mass
spectrometry showed that the TIS cells contain different glycan modifying enzymes. The lectin, calnexin
demonstrated a lower kDa size (B58 kDa) in TIS compared to control cells (B90 kDa) while Galectin 3
demonstrated potential proteolytic cleavage with 32 kDa and B22 kDa bands evident in TIS compared
to non-senescent control cells with a major 32 kDa band only. TIS CAL51 cells also demonstrated a
reduced adhesion to collagen I compared to control non-senescent cells. This study has shown that therapeutic-induced-senescent TNBC cells and their EV progeny, display differential N-glycan moieties compared to non-senescent Cal51 cells and their resultant EV progeny. For the future, N-glycan moieties on cancer senescent cells and their EV progeny hold potential for (i) the monitoring of
treatment response as a liquid biopsy, and (ii) cancer senescent cell targeting with lectin therapie
Development of Oxadiazole-Sulfonamide-Based Compounds as Potential Antibacterial Agents
No full textIn this work, substituted 1,2,4-oxadiazoles (OX1−
OX27) were screened against five bacterial strains, identified to be OX7 and OX11 as growth inhibitors with minimum inhibitory concentration (MIC) values of 31.25 and 15.75 μg/mL, respectively. The growth inhibitory property of OX7 and OX11 was further validated by disk diffusion, growth curve, and time kill curve assays. Both disrupted biofilm formation with 92−100% reduction examined by the XTT assay were further visualized by scanning electron microscopy analysis. These compounds in combination with ciprofloxacin also exhibit synergy against Escherichia coli cells. With insignificant cytotoxic behavior on HEK293 cells, human red blood cells, and Galleria mellonella larvae, OX11 was tested against 28 multidrug resistant environmental
isolates of bacteria and showed inhibition of Kluyvera georgiana and Citrobacter werkmanii strains with 32 and 16 μg/mL MIC values, respectively. The synergistic behavior of OX11 with ampicillin showed many fold reductions in MIC values against K. georgiana and Klebsiella pneumoniae multidrug resistant strains. Further, transmission electron microscopy analysis of OX11-treated E. coli cells
showed a significantly damaged cell wall, which resulted in the loss of integrity and cytosolic oozing. OX11 showed significant changes in the secondary structure of human serum albumin (HSA) in the presence of OX11, enhancing HSA stability. Overall, the study provided a suitable core for further synthetic alterations and development as an antibacterial agen
Assessment of Dihydro[1,3]oxazine‐Fused Isoflavone and 4‐Thionoisoflavone Hybrids as Antibacterials
No full textA series of isoflavone functionalized 3,4-dihydro-1,3-oxazine hybrids was synthesized in good to excellent yields through a Mannich-type condensation cyclization reaction of 6-chloro-7-hydroxy-3-(2-methoxy-phenyl)-chromen-4-one or 6-chloro-7-hydroxy-3-(2-methoxy-phenyl)-chromene-4-thione with
formaldehyde and primary amines. After spectroscopic characterization, these newly prepared hybrids were evaluated for their antibacterial activities against two of each Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains.
Among the screened compounds, dihydro[1,3]oxazine-fused 4-
thionoisoflavones(9band9c) exhibited potent inhibitory activity against all the tested bacterial species. Moreover, compound 9b possessed most promising antibacterial activity against P. aeruginosa and B. subtiliswith MIC 16 μg/mL and S. aureusand E.coliwith MIC 32 μg/mL. Further, 9bdemonstrated better efficacy (MIC=16 μg/mL) than the standard drug ampicillin (MIC= 32 μg/mL) against P. aeruginosaand it also found to be equipotent (MIC=16 μg/mL) as ampicillin against B. subtilis.
Considering the disk diffusion and synergistic studies, 9be�merged asmost active compound showing potent activity
against all the tested bacterial strains. In addition, no significant hemolysis or cytotoxicity was observed towards human embryonic kidney (HEK293)cells as well as Galleria mellonellalarvae (in vivo). Hence, compound 9bhas potential to be further explored alone and in combination with ampicillin as a next generation antibacterial agent