The design and relevance of a computerised therapy program for indigenous Māori adolescents.

Background: Depression is a major health issue among Māori indigenous adolescents, yet there has been little investigation into the relevance or effectiveness of psychological treatments for them. Further, consumer views are critical for engagement and adherence to therapy. However, there is little research regarding indigenous communities’ opinions about psychological interventions for depression. Objective: The objective of this study was to conduct semistructured interviews with Māori (indigenous New Zealand) young people (taitamariki) and their families to find out their opinions of a prototype computerized cognitive behavioral therapy (cCBT) program called Smart, Positive, Active, Realistic, X-factor thoughts (SPARX), a free online computer game intended to help young persons with mild to moderate depression, feeling down, stress or anxiety. The program will teach them how to resolve their issues on their own using Cognitive Behavioural Therapy as psychotherapeutic approach. Methods: There were seven focus groups on the subject of the design and cultural relevance of SPARX that were held, with a total of 26 participants (19 taitamarki, 7 parents/caregivers, all Māori). There were five of the groups that were with whānau (family groups) (n=14), one group was with Māori teenage mothers (n=4), and one group was with taitamariki (n=8). The general inductive approach was used to analyze focus group data. Results: SPARX computerized therapy has good face validity and is seen as potentially effective and appealing for Māori people. Cultural relevance was viewed as being important for the engagement of Māori young people with SPARX. Whānau are important for young peoples’ well-being. Participants generated ideas for improving SPARX for Māori and for the inclusion of whānau in its delivery. Conclusions: SPARX computerized therapy had good face validity for indigenous young people and families. In general, Māori participants were positive about the SPARX prototype and considered it both appealing and applicable to them. The results of this study were used to refine SPARX prior to it being delivered to taitamariki and non-Māori young people

Genetic determination of exocrine pancreatic function in cystic fibrosis

We showed elsewhere that the pancreatic function status of cystic fibrosis (CF) patients could be correlated to mutations in the CF transmembrane conductance regulator (CFTR) gene. Although the majority of CF mutations- including the most common, ΔF508-strongly correlated with pancreatic insufficiency (PI), approximately 10% of the mutant alleles may confer pancreatic sufficiency (PS). To extend this observation, genomic DNA of 538 CF patients with well-documented pancreatic function status were analyzed for a series of known mutations in their CFTR genes. Only 20 of the 25 mutations tested were found in this population. They accounted for 84% of the CF chromosomes, with ΔF508 being the most frequent (71%), and the other mutations accounted for less than 5% each. A total of 30 different, complete genotypes could be determined in 394 (73%) of the patients. The data showed that each genotype was associated only with PI or only with PS, but not with both. This result is thus consistent with the hypothesis that PI and PS in CF are predisposed by the genotype at the CFTR locus; the PS phenotype occurs in patients who have one or two mild CFTR mutations, such as R117H, R334W, R347P, A455E, and P574H, whereas the PI phenotype occurs in patients with two severe alleles, such as ΔF508, ΔI507, Q493X, G542X, R553X, W1282X, 621 + 1G→T, 1717-1G→A, 556delA, 3659delC, I148T, G480C, V520F, G551D, and R560T.published_or_final_versio

Tauiwi general practitioners explanations of Maori health: Colonial relations in primary healthcare in Aotearoa/New Zealand?

This paper reports initial findings from qualitative research investigating how general practitioners talk about Maori health. Transcripts of semi-structured interviews with 25 general practitioners from urban Auckland were subjected to critical discursive analyses. Through this process of intensive, analytic reading, interpretative repertoires – patterns of words and images about a particular topic – were identified. This paper presents the main features of one such repertoire, termed Maori Morbidity, that the general practitioners used in accounting for poor Maori health status. Our participants were drawing upon a circumscribed pool of ideas and explaining the inequalities in health between Maori and Tauiwi in ways that gave primacy to characteristics of Maori and their culture. We discuss the implications of this conclusion for relations between Maori patients and Tauiwi doctors in primary healthcare settings

Reimagining how organisations can design, build, and maintain effective net zero Multi-Stakeholder Partnerships: embracing the enabling Mechanisms to help the UK accelerate to its net zero by 2050 Grand Challenge

The net zero by 2050 policy Grand Challenge is a complex, multifaceted change project that impacts every aspect of society. As of 2024, the UK is behind its intended net zero policy trajectory; accelerated decarbonisation is now crucial and organisations play a key role. Prior research has highlighted the significance of organisational Multi-Stakeholder Partnerships (MSPs) in addressing society’s Grand Challenges, including net zero. MSPs share resources, risks, and benefits, and their scale facilitates the necessary levels of change to deliver impact. This study builds upon this thinking, advancing it by reimagining how organisations can design, build, and maintain MSPs more easily, ultimately decarbonising faster. The study adopts a realist-based philosophy and employs a Context, Mechanism, and Outcome approach as its central framework. By understanding the UK’s net zero Context and the Mechanisms that shape the net zero logic, the study identifies important organisational barriers and enabling Mechanisms that can encourage organisational collaboration and more effective MSPs. Employing a mixed methods approach, this research delves into the organisational reality of sustainability leaders and their decarbonisation challenges. By employing a range of theories and concepts, including stakeholder and institutional theory, Grand Challenge and Boundary Spanners, the study uncovers four key themes providing a comprehensive understanding of how to design, build, and maintain stronger MSPs, ultimately enabling the outcome of faster decarbonisation. The study reveals that while net zero MSPs are ideally suited to this societal Grand Challenge, only 22% of organisations in the UK are engaged in them. Instead, simpler Dyadic-Stakeholder Partnerships (DSPs) are more common. To address this reality and lead organisations to successful net zero outcomes, the study provides three novel contributions. Firstly, it designs a net zero MSP framework plus a transition pathway organisations can follow to convert DSPs to MSPs. These use a range of enabling Mechanisms including the power derived from aligning the key attributes from stakeholder and institutional theory. Secondly, the study reframes net zero as a Grand Challenge brand. This is also an MSP enabling mechanism. Sorting and resolving net zero is unrealistic, but by being flexible, agile and recognising that obstacles need to be overcome, organisations can navigate net zero’s complexity by embracing the cross-functional enabling power of the Grand Challenge brand. The third contribution reinvents the Boundary Spanner as a net zero MSP designer, builder, and maintainer with enabling agency power. Furthermore, adding practical value to this contribution, the study details the role, responsibilities and behaviours of the net zero MSP Boundary Spanner and proposes the ‘Six Characteristics of a net zero MSP Boundary Spanner’. These contributions, as net zero MSP enabling mechanisms, have causal power to effect organisational change, giving organisations of all sizes the potential to participate in net zero MSPs and help accelerate the UK to net zero by 2050

Longitudinal evaluation of quality of life in 288 patients with neurofibromatosis 2

Advances in molecular biology have resulted in novel therapy for neurofibromatosis 2-related (NF2) tumours, highlighting the need for robust outcome measures. The disease-focused NF2 impact on quality of life (NFTI-QOL) patient questionnaire was assessed as an outcome measure for treatment in a multi-centre study. NFTI-QOL was related to clinician-rated severity (ClinSev) and genetic severity (GenSev) over repeated visits. Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach's alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p <0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p <0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p <0.001; r = 0.42 for all visits). NFTI-QOL showed a good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype. © 2014 The Author(s)

James Hutton’s geological tours of Scotland : romanticism, literary strategies, and the scientific quest

This article explores a somewhat neglected part of the story of the emergence of geology as a science and discourse in the late eighteenth century – James Hutton’s posthumously published accounts of the geological tours of Scotland that he undertook in the years 1785 to 1788 in search of empirical evidence in support of his theory of the Earth and that he intended to include in the projected third volume of his Theory of the Earth of 1795. The article brings some of the assumptions and techniques of literary criticism to bear on Hutton’s scientific travel writing in order to open up new connections between geology, Romantic aesthetics and eighteenth-century travel writing about Scotland. Close analysis of Hutton’s accounts of his field trips to Glen Tilt, Galloway and Arran, supplemented by later accounts of the discoveries at Jedburgh and Siccar Point, reveals the interplay between desire, travel and the scientific quest and foregrounds the textual strategies that Hutton uses to persuade his readers that they share in the experience of geological discovery and interpretation as ‘virtual witnesses’. As well as allowing us to revisit the interrelation between scientific theory and discovery, this article concludes that Hutton was a much better writer than he has been given credit for and suggests that if these geological tours had been published in 1795 they would have made it impossible for critics to dismiss him as an armchair geologist

Proceedings of a Hui held at Hirangi Marae, Turangi

This article is a report based on the deliberations of a national Māori Hui held at the Hirangi marae, Turangi on Sunday 29 January 1995. Sir Hepi Te Heuheu called the Hui in response to the Government's Proposals for the Settlement of Treaty of Waitangi Claims and to consider how the rangatiratanga of Iwi might be advanced. The report discusses some preliminary considerations. The report then criticises the process adopted to develop the Proposal, including its lack of genuine consultation. The report then discusses the principles underlying the Proposal, the assumptions made by the Proposal, and the Proposal's settlement framework. An alternative approach is provided by the report, mostly focusing on constitutional change. The final part of the report contains substantive recommendations for the Crown.&nbsp

hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2/S6K2 signalling

The increased cap-independent translation of anti-apoptotic proteins is involved in the development of drug resistance in lung cancer but signalling events regulating this are poorly understood. Fibroblast growth factor 2 (FGF-2) signalling-induced S6 kinase 2 (S6K2) activation is necessary, but the downstream mediator(s) coupling this kinase to the translational response is unknown. Here, we show that S6K2 binds and phosphorylates hnRNPA1 on novel Ser4/6 sites, increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export. In the cytoplasm, phosphoS4/6-hnRNPA1 dissociates from these mRNAs de-repressing their IRES-mediated translation. This correlates with the phosphorylation-dependent association of hnRNPA1 with 14-3-3 leading to hnRNPA1 sumoylation on K183 and its re-import into the nucleus. A non-phosphorylatible, S4/6A mutant prevented these processes, hindering the pro-survival activity of FGF-2/S6K2 signalling. Interestingly, immunohistochemical staining of lung and breast cancer tissue samples demonstrated that increased S6K2 expression correlates with decreased cytoplasmic hnRNPA1 and increased BCL-XL expression. In short, phosphorylation on novel N-term sites of hnRNPA1 promotes translation of anti-apoptotic proteins and is indispensable for the pro-survival effects of FGF-2

Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial.

We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2-26.4%), compared with 6.5% (95% CI 0.2-12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk

Salmonella enterica biofilm-mediated dispersal by nitric oxide donors in association with cellulose nanocrystal hydrogels

Protected by extracellular polymers, microbes within biofilms are significantly more resistant to disinfectants. Current research has been instrumental in identifying nitric oxide donors and hydrogels as potential disinfectant additives. Nitric oxide (NO) donors are considered a very promising molecule as biofilm dispersal agents and hydrogels have recently attracted a lot of interest due to their biocompatible properties and ability to form stable thin films. When the NO donor MAHMA NONOate was dissolved in phosphate saline buffer, it was able to reduce the biomass of well-established biofilms up to 15% for at least 24 h of contact time. Encapsulation of MAHMA NONOate and molsidomine within a hydrogel composed of cellulose nanocrystals (CNC) has shown a synergistic effect in dispersing well-established biofilms: after 2 h of exposure, moderate but significant dispersion was measured. After 6 h of exposure, the number of cells transitioning from the biofilm to the planktonic state was up to 0.6 log higher when compared with non-treated biofilms. To further explore the transport processes of NO donors within hydrogels, we measured the nitric oxide flux from gels, at 25°C for a composite of 0.1 µM MAHMA NONOate–CNC. Nitric oxide diffuses up to 500 µm from the hydrogel surface, with flux decreasing according to Fick’s law. 60% of NO was released from the hydrogel composite during the first 23 min. These data suggest that the combined treatments with nitric oxide donor and hydrogels may allow for new sustainable cleaning strategies