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1.
Nature ; 620(7976): 1018-1024, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37612503

RESUMO

Coral reefs are highly diverse ecosystems that thrive in nutrient-poor waters, a phenomenon frequently referred to as the Darwin paradox1. The energy demand of coral animal hosts can often be fully met by the excess production of carbon-rich photosynthates by their algal symbionts2,3. However, the understanding of mechanisms that enable corals to acquire the vital nutrients nitrogen and phosphorus from their symbionts is incomplete4-9. Here we show, through a series of long-term experiments, that the uptake of dissolved inorganic nitrogen and phosphorus by the symbionts alone is sufficient to sustain rapid coral growth. Next, considering the nitrogen and phosphorus budgets of host and symbionts, we identify that these nutrients are gathered through symbiont 'farming' and are translocated to the host by digestion of excess symbiont cells. Finally, we use a large-scale natural experiment in which seabirds fertilize some reefs but not others, to show that the efficient utilization of dissolved inorganic nutrients by symbiotic corals established in our laboratory experiments has the potential to enhance coral growth in the wild at the ecosystem level. Feeding on symbionts enables coral animals to tap into an important nutrient pool and helps to explain the evolutionary and ecological success of symbiotic corals in nutrient-limited waters.


Assuntos
Antozoários , Ecossistema , Nitrogênio , Fósforo , Fotossíntese , Simbiose , Animais , Antozoários/crescimento & desenvolvimento , Antozoários/metabolismo , Antozoários/fisiologia , Nitrogênio/metabolismo , Fósforo/metabolismo , Simbiose/fisiologia , Aves/fisiologia
2.
J Am Chem Soc ; 146(28): 19177-19182, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38953610

RESUMO

The development of intrinsically recyclable cross-linked materials remains challenged by the inherently unfavorable chemical equilibrium that dictates the efficiency of the reversible covalent bonding/debonding chemistry. Rather than having to (externally) manipulate the bonding equilibrium, we here introduce a new reversible chemistry platform based on monosubstituted thiomaleimides that can undergo complete and independent light-activated covalent bonding and on-demand thermal debonding above 120 °C. Specifically, repeated bonding/debonding of a small-molecule thiomaleimide [2 + 2] photodimer is demonstrated over five heat/light cycles with full conversion in both directions, thereby regenerating its initial monothiomaleimide constituents. This motivated the synthesis of multifunctional thiomaleimide reagents as precursors for the design of covalently cross-linked networks that display intrinsic switching between a monomeric and polymeric state. The resulting materials are shown to covalently dissociate and depolymerize upon heating both in solution and in bulk, thus transforming the densely photo-cross-linked material back into a viscous liquid. Temperature-regulated photorheology evidenced the intrinsic recyclability of the thiomaleimide-based thermosets during multiple cycles of UV cross-linking and thermal de-cross-linking. The thermally reversible photodimerization of thiomaleimides presents a new addition to the designer playground of dynamic polymer networks, providing interesting opportunities for the reprocessing and closed-loop recycling of covalently cross-linked materials.

3.
Biochem Biophys Res Commun ; 738: 150517, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39146620

RESUMO

Here we report that simultaneous inhibition of the three primary DNA damage recognition PI3 kinase-like kinases (PIKKs) -ATM, ATR, and DNA-PK- induces severe combinatorial synthetic lethality in mammalian cells. Utilizing Chinese hamster cell lines CHO and V79 and their respective PIKK mutants, we evaluated effects of inhibiting these three kinases on cell viability, DNA damage response, and chromosomal integrity. Our results demonstrate that while single or dual kinase inhibition increased cytotoxicity, inhibition of all three PIKKs results in significantly higher synergistic lethality, chromosomal aberrations, and DNA double-strand break (DSB) induction as calculated by their synergy scores. These findings suggest that the overlapping redundancy of ATM, ATR, and DNA-PK functions is critical for cell survival, and their combined inhibition greatly disrupts DNA damage signaling and repair processes, leading to cell death. This study provides insights into the potential of multi-targeted DDR kinase inhibition as an effective anticancer strategy, necessitating further research to elucidate underlying mechanisms and therapeutic applications.

4.
Pharmacogenomics J ; 24(5): 25, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122683

RESUMO

Pharmacogenetic testing in the United Kingdom's National Health Service (NHS) has historically been reactive in nature, undertaken in the context of single gene-drug relationships in specialist settings. Using a discrete choice experiment we aimed to identify healthcare professional preferences for development of a pharmacogenetic testing service in primary care in the NHS. Respondents, representing two professions groups (general practitioners or pharmacists), completed one of two survey versions, asking them to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or joint pain. Responses from 235 individuals were included. All respondents preferred pharmacogenetic testing over no testing, though preference heterogeneity was identified. Both professional groups, but especially GPs, were highly sensitive to service design, with uptake varying depending on the service offered. This study demonstrates uptake of a pharmacogenetic testing service is impacted by service design and highlights key areas which should be prioritised within future initiatives.


Assuntos
Clínicos Gerais , Farmacêuticos , Testes Farmacogenômicos , Atenção Primária à Saúde , Humanos , Testes Farmacogenômicos/métodos , Masculino , Feminino , Reino Unido , Adulto , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Inquéritos e Questionários , Comportamento de Escolha , Farmacogenética/métodos
5.
Bioconjug Chem ; 35(3): 400-411, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38366969

RESUMO

Photodynamic therapy (PDT) is a cancer treatment strategy that utilizes photosensitizers to convert oxygen within tumors into reactive singlet oxygen (1O2) to lyse tumor cells. Nevertheless, pre-existing tumor hypoxia and oxygen consumption during PDT can lead to an insufficient oxygen supply, potentially reducing the photodynamic efficacy. In response to this issue, we have devised a pH-responsive amphiphilic triblock fluorinated polymer (PDP) using copper-mediated RDRP. This polymer, composed of poly(ethylene glycol) methyl ether acrylate, 2-(diethylamino)ethyl methacrylate, and (perfluorooctyl)ethyl acrylate, self-assembles in an aqueous environment. Oxygen, chlorine e6 (Ce6), and doxorubicin (DOX) can be codelivered efficiently by PDP. The incorporation of perfluorocarbon into the formulation enhances the oxygen-carrying capacity of PDP, consequently extending the lifetime of 1O2. This increased lifetime, in turn, amplifies the PDT effect and escalates the cellular cytotoxicity. Compared with PDT alone, PDP@Ce6-DOX-O2 NPs demonstrated significant inhibition of tumor growth. This study proposes a novel strategy for enhancing the efficacy of PDT.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Humanos , Polímeros de Fluorcarboneto , Oxigênio , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia/tratamento farmacológico , Concentração de Íons de Hidrogênio
6.
Br J Clin Pharmacol ; 90(7): 1699-1710, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38616172

RESUMO

AIMS: Genetic testing can be used to improve the safety and effectiveness of commonly prescribed medicines-a concept known as pharmacogenetics. This study aimed to quantify members of the UK public's preferences for a pharmacogenetic service to be delivered in primary care in the National Health Service. METHODS: Members of the UK population were surveyed via an online panel company. Respondents completed 1 of 2 survey versions, asking respondents to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or pain. A conditional logit model was estimated, before the best functional form for the dataset was identified. Preference heterogeneity was identified via latent class analysis. Coefficients from the final selected models were used to estimate uptake in the context of different hypothetical pharmacogenetic services. RESULTS: Responses from 1993 individuals were included in the analysis. There were no differences observed in preference between the 2 clinical scenarios. Conditional logit analysis, using maximum likelihood estimation, indicated that respondents preferred to have noninvasive tests and wanted their data to be shared between different healthcare organizations to guide future prescribing. There was a preference for regional over national data sharing initiatives, and respondents preferred to have access to their data. Predicted uptake varied considerably, ranging from 51% to >99%, depending on design of the service. CONCLUSION: This study identifies public preferences for a pharmacogenetic testing service and demonstrates how predicted uptake can be impacted by relatively minor adaptations. This highlights areas for prioritization during development of future pharmacogenetic services.


Assuntos
Testes Farmacogenômicos , Medicina Estatal , Humanos , Testes Farmacogenômicos/métodos , Masculino , Feminino , Reino Unido , Adulto , Pessoa de Meia-Idade , Idoso , Inquéritos e Questionários , Adulto Jovem , Preferência do Paciente , Adolescente , Comportamento de Escolha , Farmacogenética , Atenção Primária à Saúde
7.
Macromol Rapid Commun ; 45(8): e2300692, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38288674

RESUMO

Measurement of molecular weight is an integral part of macromolecular and polymer characterization which usually has limitations. Herein, this article presents the use of a bench-top 80 MHz Nuclear Magnetic Resonance (NMR) spectrometer for diffusion-ordered spectroscopy as a practical and rapid approach for the determination of molecular weight/size using a novel solvent and polymer-independent universal calibration.


Assuntos
Substâncias Macromoleculares , Espectroscopia de Ressonância Magnética , Peso Molecular , Polímeros , Polímeros/química , Espectroscopia de Ressonância Magnética/métodos , Substâncias Macromoleculares/química , Difusão
8.
Phys Chem Chem Phys ; 26(35): 22912-22930, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39171363

RESUMO

Lysosome imaging plays an important role in diagnosing many diseases and understanding various intracellular processes. Recently, B0 was reported as a fluorescent probe capable of detecting lysosomal viscosity changes. BODIPY is fused into the molecule as a bridge between the acceptor and donor components of B0, yielding nine new B molecules. Computational design and analysis of their optoelectronic properties were conducted to evaluate their effectiveness as fluorescent probes for lysosome imaging, with a specific target of HSA inside lysosomes. Optimized geometries reveal excellent π electron delocalization, resulting in nearly planar molecular structures. Frontier molecular orbital analysis suggests intramolecular charge transfer, along with π-π* transitions, from donor to bridge. TD-DFT calculations were performed to study absorption properties in the solvent phase, with B3PW91 showing good agreement with experiments. Molecular docking studies indicate that B derivatives can bind with HSA, and molecular dynamics simulations confirm their HSA targeting ability. This investigation highlights the introduction of BODIPY as a bridge for developing new probes capable of producing NIR fluorescence for bio-imaging, aiding in disease diagnosis.


Assuntos
Compostos de Boro , Corantes Fluorescentes , Lisossomos , Simulação de Acoplamento Molecular , Corantes Fluorescentes/química , Compostos de Boro/química , Lisossomos/química , Lisossomos/metabolismo , Humanos , Simulação de Dinâmica Molecular , Teoria da Densidade Funcional , Albumina Sérica Humana/química , Estrutura Molecular , Imagem Óptica
10.
J Med Internet Res ; 26: e55546, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39321457

RESUMO

BACKGROUND: Approximately 4.5 million people live with type 2 diabetes mellitus (T2DM) in the United Kingdom. Evidence shows that structured education programs can improve glycemic control and reduce the risk of complications from T2DM, but they have low attendance rates. To widen access to T2DM structured education, National Health Service England commissioned a national rollout of Healthy Living, a digital self-management program. OBJECTIVE: The objectives were to understand the barriers and enablers to adopting, implementing, and integrating Healthy Living into existing T2DM care pathways across England. METHODS: We undertook a cross-sectional, qualitative telephone semistructured interview study to address the objectives. In total, 17 local National Health Service leads responsible for implementing Healthy Living across their locality were recruited. We conducted 16 one-time interviews across 16 case sites (1 of the interviews was conducted with 2 local leads from the same case site). Interview data were analyzed using thematic analysis. RESULTS: Three overarching themes were generated: (1) implementation activities, (2) where Healthy Living fits within existing pathways, and (3) contextual factors affecting implementation. Of the 16 sites, 14 (88%) were implementing Healthy Living; the barrier to not implementing it in 2 case sites was not wanting Healthy Living to compete with their current education provision for T2DM. We identified 6 categories of implementation activities across sites: communication strategies to raise awareness of Healthy Living, developing bespoke local resources to support general practices with referrals, providing financial reimbursement or incentives to general practices, promoting Healthy Living via public events, monitoring implementation across their footprint, and widening access across high-need groups. However, outside early engagement sites, most implementation activities were "light touch," consisting mainly of one-way communications to raise awareness. Local leads were generally positive about Healthy Living as an additional part of their T2DM structured education programs, but some felt it was more suited to specific patient groups. Barriers to undertaking more prolonged, targeted implementation campaigns included implementation not being mandated, sites not receiving data on uptake across their footprint, and confusion in understanding where Healthy Living fit within existing care pathways. CONCLUSIONS: A passive process of disseminating information about Healthy Living to general practices rather than an active process of implementation occurred across most sites sampled. This study identified that there is a need for clearer communications regarding the type of patients that may benefit from the Healthy Living program, including when it should be offered and whether it should be offered instead of or in addition to other education programs. No sites other than early engagement sites received data to monitor uptake across their footprint. Understanding variability in uptake across practices may have enabled sites to plan targeted referral campaigns in practices that were not using the service.


Assuntos
Diabetes Mellitus Tipo 2 , Pesquisa Qualitativa , Autogestão , Diabetes Mellitus Tipo 2/terapia , Humanos , Autogestão/métodos , Estudos Transversais , Medicina Estatal , Inglaterra , Entrevistas como Assunto , Reino Unido
11.
J Adv Nurs ; 80(8): 3359-3370, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38186205

RESUMO

AIM: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity. DESIGN: An interpretive, descriptive, qualitative interview study. METHODS: Data were collected using semi-structured interviews undertaken between January and November 2020. Participants were neonatal intensive care nursing staff taking part in the Pharmacogenetics to Avoid Loss of Hearing trial. RESULTS: Thematic analysis resulted in four themes: perceived clinical utility; the golden hour; point-of-care device; training and support. Recommendations were made to streamline the protocol and ongoing training and support were considered key to incorporating the test into routine care. CONCLUSION: Exploring the views of nurses involved in the delivery of the point-of-care test was essential in its implementation. By the study endpoint, all participants could see the value of routine clinical introduction of the point-of care test. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses are in a key position to support the delivery of point-of-care genetic testing into mainstream settings. This study has implications for the successful integration of other genetic point-of-care tests in acute healthcare settings. IMPACT: The study will help to tailor the training and support required for routine deployment of the genetic point-of-care test. The study has relevance for nurses involved in the development and delivery of genetic point-of-care tests in other acute hospital settings. REPORTING METHOD: This qualitative study adheres to the Standards for Reporting Qualitative Research EQUATOR guidelines and utilizes COREQ and SRQR checklists. PATIENT OR PUBLIC CONTRIBUTION: All staff working on the participating neonatal intensive care units were trained to use the genetic point-of-care test. All inpatients on the participating units were eligible to have testing via the point-of-care test. The Pharmacogenetics to Avoid Loss of Hearing Patient and Public Involvement and Engagement group provided valuable feedback. TRIAL AND PROTOCOL REGISTRATION: Registered within the University of Manchester. Ethics approval reference numbers: IRAS: 253102 REC reference: 19/NW/0400. Also registered with the ISRCTN ref: ISRCTN13704894.


Assuntos
Antibacterianos , Unidades de Terapia Intensiva Neonatal , Testes Imediatos , Pesquisa Qualitativa , Humanos , Recém-Nascido , Antibacterianos/efeitos adversos , Feminino , Masculino , Ototoxicidade , Atitude do Pessoal de Saúde , Recursos Humanos de Enfermagem Hospitalar , Adulto , Sistemas Automatizados de Assistência Junto ao Leito , Testes Genéticos
12.
Surgeon ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39368884

RESUMO

INTRODUCTION: The United Kingdom (UK) and world's population is aging with patients living longer, often with many co-morbidities. It is expected that patients of extreme old age would have poor outcomes following trauma; however, this assumption is not clearly evidenced. This study aims to present the outcomes of patients aged 100 or older admitted to a single hospital trust following admission for orthopaedic trauma. METHOD: A prospective cohort of patients aged 100 years and over admitted to the trauma and orthopaedic departments of two hospitals within the same trust between 2008 and 2022 was reviewed. Age was median 101 years (100-106 years). Outcome measures were length of stay, survival, complications and change in accommodation. RESULTS: 80 patients met the inclusion criteria (71female, 9 male). Mean age at discharge was 102.5 years with survival mean 4.2 years. 2 patients with peri-prosthetic fracture survived a further 5 years. Mean length of stay was 17 days. 57 patients returned to their original place of residence. 72 patients (90 %) survived the acute hospital admission. CONCLUSION: Survival rates for patients aged over 100 years were high and most returned to the previous place of residence. This study supports the surgical management of trauma and helps inform patients and families expectations for mortality risk.

13.
Glob Chang Biol ; 29(15): 4279-4297, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37100767

RESUMO

There are limited data for greenhouse gas (GHG) emissions from smallholder agricultural systems in tropical peatlands, with data for non-CO2 emissions from human-influenced tropical peatlands particularly scarce. The aim of this study was to quantify soil CH4 and N2 O fluxes from smallholder agricultural systems on tropical peatlands in Southeast Asia and assess their environmental controls. The study was carried out in four regions in Malaysia and Indonesia. CH4 and N2 O fluxes and environmental parameters were measured in cropland, oil palm plantation, tree plantation and forest. Annual CH4 emissions (in kg CH4 ha-1 year-1 ) were: 70.7 ± 29.5, 2.1 ± 1.2, 2.1 ± 0.6 and 6.2 ± 1.9 at the forest, tree plantation, oil palm and cropland land-use classes, respectively. Annual N2 O emissions (in kg N2 O ha-1 year-1 ) were: 6.5 ± 2.8, 3.2 ± 1.2, 21.9 ± 11.4 and 33.6 ± 7.3 in the same order as above, respectively. Annual CH4 emissions were strongly determined by water table depth (WTD) and increased exponentially when annual WTD was above -25 cm. In contrast, annual N2 O emissions were strongly correlated with mean total dissolved nitrogen (TDN) in soil water, following a sigmoidal relationship, up to an apparent threshold of 10 mg N L-1 beyond which TDN seemingly ceased to be limiting for N2 O production. The new emissions data for CH4 and N2 O presented here should help to develop more robust country level 'emission factors' for the quantification of national GHG inventory reporting. The impact of TDN on N2 O emissions suggests that soil nutrient status strongly impacts emissions, and therefore, policies which reduce N-fertilisation inputs might contribute to emissions mitigation from agricultural peat landscapes. However, the most important policy intervention for reducing emissions is one that reduces the conversion of peat swamp forest to agriculture on peatlands in the first place.


Assuntos
Dióxido de Carbono , Gases de Efeito Estufa , Humanos , Dióxido de Carbono/análise , Metano/análise , Agricultura , Solo , Gases de Efeito Estufa/análise , Árvores , Indonésia , Nitrogênio , Óxido Nitroso/análise
14.
Diabet Med ; 40(11): e15209, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37634235

RESUMO

AIMS: The NHS Diabetes Prevention Programme (NHS DPP) is a large-scale, England-wide behaviour change programme for people at high risk of progressing to type 2 diabetes. We summarise the findings of our six-year DIPLOMA evaluation of its implementation and impact and highlight insights for future programmes. METHODS: Using qualitative interviews, document analysis, observation, surveys and large dataset analysis, eight interlinked work packages considered: equity of access; implementation; service delivery and fidelity; programme outcomes; comparative effectiveness and cost-effectiveness in reducing diabetes incidence; and patient decision making and experience. RESULTS: Delivery of the NHS DPP encountered barriers across many aspects of the programme, and we identified inequalities in terms of the areas, organisations and patient populations most likely to engage with the programme. There was some loss of fidelity at all stages from commissioning to participant understanding. Despite these challenges, there was evidence of significant reductions in diabetes incidence at individual and population levels. The programme was cost-effective even within a short time period. CONCLUSIONS: Despite the challenge of translating research evidence into routine NHS delivery at scale, our findings suggest that an individual-level approach to the prevention of type 2 diabetes in a 'high-risk' population was more effective than usual care. By embedding evaluation with programme delivery and working closely with the NHS DPP team, we provided actionable insights for improving communications with potential participants, supporting primary care referral, honing the delivery model with better provider relationships and more patient choice, increasing understanding of behaviour change techniques, and enriching the educational and health coaching content.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Medicina Estatal , Inglaterra/epidemiologia , Fatores de Risco , Terapia Comportamental/métodos
15.
Soft Matter ; 19(20): 3711-3722, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37190902

RESUMO

Understanding the behaviour of human blood outside of the body has important implications in forensic research, especially related to bloodstain pattern analysis (BPA). The design of forensic blood substitutes (FBSs) can provide many advantages, including the incorporation of multiple physiological components for use as safe and reliable materials for forensic applications. In this work, we present the design of synthetic alginate and xanthan gum-based hydrogels that contain electrosprayed microparticles (MPs) with and without crosslinked DNA. In addition to the MPs, the alginate/xanthan gum FBS materials include fillers to alter the physical appearance and fluid properties of the material. The optimized FBS consisted of alginate (1% w/v) and xanthan gum (5.0 × 10-3% w/v), 2 mM CaCl2, ferric citrate (0.5% w/v), magnesium silicate (0.25% w/v), Allura Red dye (2% w/v), 0.025% v/v Tween 20 and 9.5% v/v MPs. The FBS was tested in passive dripping experiments relevant to BPA scenarios at various impact angles. The spreading ratio (Ds/D0) was determined for 90° stains made on a paper surface and compared to bovine blood where the FBS was shown to simulate accurate and predictable spreading behaviour. In addition, we simulated other common BPA scenarios (e.g., impact patterns) and evidence processing potential. The FBS could be swabbed, and the DNA could be extracted, amplified, and genotyped analogous to human blood evidence. A stability test was also conducted which revealed a shelf-life of over 4 weeks where the material remains relevant to human blood at physiological temperature.


Assuntos
Manchas de Sangue , Substitutos Sanguíneos , Animais , Bovinos , Humanos , Hidrogéis , Alginatos , Polissacarídeos Bacterianos
16.
BMC Health Serv Res ; 23(1): 1043, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773125

RESUMO

BACKGROUND: The National Health Service Diabetes Prevention Programme (NHS DPP) was commissioned by NHS England in 2016 and rolled out in three 'waves' across the whole of England. It aims to help people with raised blood glucose levels reduce their risk of developing type 2 diabetes through behaviour change techniques (e.g., weight loss, dietary changes and exercise). An independent, longitudinal, mixed methods evaluation of the NHS DPP was undertaken. We report the findings from the implementation work package: a qualitative interview study with designated local leads, responsible for the local commissioning and implementation of the programme. The aim of the study was to explore how local implementation processes were enacted and adapted over time. METHODS: We conducted a telephone interview study across two time-points. Twenty-four semi-structured interviews with local leads across 19 sampled case sites were undertaken between October 2019 and January 2020 and 13 interviews with local leads across 13 sampled case sites were conducted between July 2020 and August 2020. Interviews aimed to reflect on the experience of implementation and explore how things changed over time. RESULTS: We identified four overarching themes to show how implementation was locally enacted and adapted across the sampled case sites: 1. Adapting to provider change; 2. Identification and referral; 3. Enhancing uptake in underserved populations; and 4. Digital and remote service options. CONCLUSION: This paper reports how designated local leads, responsible for local implementation of the NHS DPP, adapted implementation efforts over the course of a changing national diabetes prevention programme, including how local leads adapted implementation during the COVID-19 pandemic. This paper highlights three main factors that influence implementation: the importance of facilitation, the ability (or not) to tailor interventions to local needs and the role of context in implementation.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Medicina Estatal , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pesquisa Qualitativa
17.
Proc Natl Acad Sci U S A ; 117(49): 30980-30987, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33229561

RESUMO

Sea-level rise resulting from the instability of polar continental ice sheets represents a major socioeconomic hazard arising from anthropogenic warming, but the response of the largest component of Earth's cryosphere, the East Antarctic Ice Sheet (EAIS), to global warming is poorly understood. Here we present a detailed record of North Atlantic deep-ocean temperature, global sea-level, and ice-volume change for ∼2.75 to 2.4 Ma ago, when atmospheric partial pressure of carbon dioxide (pCO2) ranged from present-day (>400 parts per million volume, ppmv) to preindustrial (<280 ppmv) values. Our data reveal clear glacial-interglacial cycles in global ice volume and sea level largely driven by the growth and decay of ice sheets in the Northern Hemisphere. Yet, sea-level values during Marine Isotope Stage (MIS) 101 (∼2.55 Ma) also signal substantial melting of the EAIS, and peak sea levels during MIS G7 (∼2.75 Ma) and, perhaps, MIS G1 (∼2.63 Ma) are also suggestive of EAIS instability. During the succeeding glacial-interglacial cycles (MIS 100 to 95), sea levels were distinctly lower than before, strongly suggesting a link between greater stability of the EAIS and increased land-ice volumes in the Northern Hemisphere. We propose that lower sea levels driven by ice-sheet growth in the Northern Hemisphere decreased EAIS susceptibility to ocean melting. Our findings have implications for future EAIS vulnerability to a rapidly warming world.

18.
J Adv Nurs ; 79(7): 2568-2584, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36811300

RESUMO

AIMS: To explore barriers to, and facilitators of, adherence to compression therapy, from the perspective of people with venous leg ulcers. DESIGN: An interpretive, qualitative, descriptive study involving interviews with patients. METHODS: Participants were purposively sampled from respondents to a survey exploring attitudes to compression therapy in people with venous leg ulcers. Sampling continued until data saturation: 25 interviews between December 2019 and July 2020. Inductive thematic analysis of interview transcripts was undertaken to create a framework for the data, followed by deductive analysis informed by the Common-Sense Model of Self-Regulation. RESULTS: A range of knowledge and understanding about the cause of venous leg ulcers and the mechanisms of compression therapy was demonstrated, which was not particularly related to adherence. Participants talked about their experience with different compression methods and their concerns about the length of time healing could take. They also spoke about aspects of the organization of services which affected their care. CONCLUSION: Identifying specific, individual barriers/facilitators to compression therapy is not simple, rather factors combine to make adherence more or less likely or possible. There was no clear relationship between an understanding of the cause of VLUs or the mechanism of compression therapy and adherence; different compression therapies presented different challenges for patients; unintentional non-adherence was frequently mentioned; and the organization of services could impact on adherence. Ways in which people could be supported to adhere to compression therapy are indicated. Implications for practice include issues relating to communication with patients; taking into account patients' lifestyles and ensuring that they know about useful 'aids'; providing services that are accessible and provide continuity of appropriately trained staff; minimizing unintentional non-adherence; and acknowledging that healthcare professionals will always need to support/advise those who cannot tolerate compression. IMPACT: Compression therapy is a cost-effective, evidence-based treatment for venous leg ulcers. However, there is evidence that patients do not always adhere to this therapy and there is limited research investigating reasons why patients do not wear compression. The study found no clear relationship between an understanding of the cause of VLUs or the mechanism of compression therapy and adherence; that different compression therapies presented different challenges for patients; that unintentional non-adherence was frequently mentioned and that the organization of services could impact on adherence. Attending to these findings offers the opportunity to increase the proportion of people undergoing appropriate compression therapy and achieving complete wound healing, the main outcome desired by this group. PATIENT/PUBLIC CONTRIBUTION: A patient representative sits on the Study Steering Group, contributing to the work from developing the study protocol and interview schedule to interpretation and discussion of findings. Members of a Wounds Research Patient and Public Involvement Forum were consulted about interview questions.


Assuntos
Úlcera da Perna , Úlcera Varicosa , Humanos , Úlcera Varicosa/terapia , Cicatrização , Resultado do Tratamento , Custos de Cuidados de Saúde , Pesquisa Qualitativa
19.
Br J Haematol ; 199(2): 277-284, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35922080

RESUMO

We describe the management and the prevalence of iron deficiency anaemia (IDA) during pregnancy by comparison to standards. A cross-sectional national cohort study of women who had given birth six weeks prior to data collection was conducted at maternity units in the UK and Ireland. Participating centres collected data from 10 consecutive pregnant women. Analysis was descriptive to define the prevalence of IDA in pregnancy and the puerperium, and to compare the outcomes in women who had IDA with women who did not have anaemia anytime during pregnancy. Eighty-six maternity units contributed data on 860 pregnancies and births. The overall prevalence of IDA during pregnancy was 30.4% and in the puerperium 20%. Anaemic women were more likely to be from ethnic minorities, odds ratio 2.23 (1.50, 3.32). Adherence to national guidance was suboptimal, and the prevalence of anaemia in pregnancy remains very high. There is pressing need to explore barriers to early identification and effective management of iron deficiency. IDA should be considered a major public health problem in the UK.


Assuntos
Anemia Ferropriva , Anemia , Deficiências de Ferro , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/terapia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Gravidez , Prevalência
20.
Thorax ; 77(9): 929-932, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35790388

RESUMO

Despite good evidence of impaired innate antiviral responses in asthma, trials of inhaled interferon-ß given during exacerbations showed only modest benefits in moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust in vivo induction of bronchial epithelial interferon response genes 4 days after virus inoculation in 25 subjects with asthma but not 11 control subjects. This signature correlated with virus loads and lower respiratory symptoms. Our data indicate that the in vivo innate antiviral response is dysregulated in asthma and open up the potential that prophylactic rather than therapeutic interferon therapy may have greater clinical benefit.


Assuntos
Asma , Imunidade Inata , Interferons , Infecções por Picornaviridae , Asma/imunologia , Asma/virologia , Células Epiteliais/imunologia , Humanos , Interferons/imunologia , Infecções por Picornaviridae/genética , Infecções por Picornaviridae/imunologia , Rhinovirus
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