Poor Uptake Research Articles

Parents’ and informal caregivers’ experiences of accessing childhood vaccination services within the United Kingdom: a systematic scoping review of empirical evidence

BackgroundDespite repeated calls to action and considerable attention, childhood vaccination uptake has declined for a thirteenth consecutive year in the United Kingdom (UK). Increasingly, stakeholders are advocating for research which goes beyond vaccine hesitancy and explores service accessibility in greater depth. This scoping review aims to identify and critically assess how accessibility is being conceptualised and investigated with a view to informing future research. Research, that in turn, will dictate the interventions pursued to improve vaccination coverage.MethodsA detailed search strategy was implemented across seven databases to identify research exploring parents’ experiences of accessing childhood vaccination services within the UK. The analysis explored the studies in relation to their conceptualisation of access, methodology, reported results, and recommendations for research or practice using a combination of descriptive qualitative content analysis, typologies, and frequency counts. Methods and reporting adhered to the ‘JBI Manual for Evidence Synthesis’ and the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews’.ResultsForty-five studies were included in the analysis. Studies claimed to consider only attitudinal constructs (4%) or did not discuss access at all (33%) despite findings, in part, including access related issues. Remaining studies used the term access in passing or ambiguously (24%), distinguished between attitudes and access in-text (27%), and a minority of studies utilised a theoretical framework which acknowledged accessibility (13%). The focus on access to information (92% of studies) was disproportionately large compared to other domains of accessibility such as availability (11%), affordability (13%), and proximity (16%). Of the seven identified intervention studies, five were centred on information provision.ConclusionAccessibility is poorly conceptualised within most of the research conducted on childhood immunisation uptake within the UK. This, in part, is because exploring accessibility was not an explicit objective of many of the studies included in the review. It is vital that the accessibility of childhood vaccination services is given greater priority and appropriately defined in empirical research. Otherwise, researchers run the risk of limiting the scope of their findings based on their own conceptual ideas regarding the drivers of poor uptake rather than the lived reality of parents.

EFFECT OF DIPOTASSIUM ETHYLENEDIAMINETETRAACETIC ACID AND LITHIUM HEPARIN ANTICOAGULANT ON HEMATOLOGIC VALUES IN THE BEARDED DRAGON (POGONA VITTICEPS) IN A CLINICAL SETTING.

Anticoagulant choice can have significant effect on complete blood counts of reptiles and has not been reported in bearded dragons (Pogona vitticeps). Whole blood was collected from 14 captive individuals and aliquoted into separate blood tubes containing dipotassium ethylenediaminetetraacetic acid (EDTA) and lithium heparin. Samples were shipped and processed within 24 h. A CBC, including a WBC count using a commercial phloxine method, was performed on blood from both tubes. A WBC estimate, WBC differential, and morphologic review were performed on blood smears made from the anticoagulated blood, as well as on a direct blood smear made from anticoagulant-free blood. Some CBC values were significantly different between the EDTA and lithium heparin samples. Hematologic data generated from direct blood smears were more similar to data from EDTA samples than to data from lithium heparin samples. Additionally, multiple lithium heparin samples had poor phloxine stain uptake and leukocyte clumping, so that many WBC parameters were altered or unreportable. These results support EDTA as an appropriate anticoagulant for bearded dragon hematologic evaluation and suggest it may be superior to heparin for some individuals in generating a WBC count using a commercial phloxine method.

Enhancing pancreatic tumor delineation using dual-energy CT-derived extracellular volume fraction map

Precise identification of pancreatic tumors is challenging for radiotherapy planning due to the anatomical variability of the tumor and poor visualization of the tumor on 3D cross-sectional imaging. Low extracellular volume fraction (ECVf) correlates with poor vasculature uptake and possible necrosis or hypoxia in pancreatic tumors. This work investigates the feasibility of delineating pancreatic tumors using ECVf spatial distribution maps derived from contrast enhanced dual-energy CT (DECT). Data acquired from radiotherapy simulation of 12 pancreatic cancer patients, using a dual source DECT scanner, were analyzed. For each patient, an ECVf distribution of the pancreas was computed from the simultaneously acquired low and high energy DECT series during the late arterial contrast phase combined with the patient's hematocrit level. Volume of interest (VECVf) maps in ECVf distribution of pancreas were identified by applying an appropriate threshold condition and a connected components clustering algorithm. The obtained VECVf was compared with the clinical gross tumor volume (GTV) using the positive predictive value (PPV), Dice similarity coefficient (DSC), mean distance to agreement (MDA) and true positive rate (TPR). As a proof of concept, our hypothetical threshold condition based on the first quartile separation of the ECVf distribution to find VECVf of the pancreas elucidates the tumor volume within the pancreas. Notably, 7 out of 12 cases studied for VECVf matched well with the GTV and the mean PPV of 0.83±0.12. The mean MDA (2.83±1.0) of the cases confirms that VECVf lies within the tolerance for comparing to the pancreatic GTV. For the remaining 5 cases, the VECVf is substantially affected by other compounding factors, e.g., large cysts, dilate ducts, and thus did not align with the GTVs. This work demonstrated the promising application of the ECVf map, derived from contrast enhanced DECT, to help delineate tumor target for RT planning of pancreatic cancer.

Evaluation of a Radioiodinated G-Quadruplex Binder in Cervical Cancer Models.

We herein describe the radiosynthesis of a 125I-labeled acridine orange derivative ([125I]-C8), acting as a G-quadruplex binder, and its biological evaluation in cervical cancer models, aiming to enlighten its potential as a radioligand for Auger Electron Radiopharmaceutical Therapy (AE-RPT) of cancer. [125I]-C8 was synthesized with a moderate radiochemical yield (ca. 60 %) by a [125I]iodo-destannylation reaction. Its evaluation in cervical cancer HeLa cells demonstrated that the radiocompound has a significant cellular internalization with a notorious accumulation in the cell nucleus. In line with these results, [125I]-C8 strongly compromised the viability of HeLa cells in a dose-dependent manner, inducing non-repairable DNA lesions that are most probably due to the AEs emitted by 125I in close proximity to the DNA molecule. Biodistribution studies in a murine HeLa xenograft model showed that [125I]-C8 has fast blood clearance and high in vivo stability but poor tumor uptake, after systemic administration. The respective supramolecular conjugate with the AS1411 aptamer ([125I]-C8/AS1411) led to a slower blood clearance in the same animal tumor model, although without improving the tumor uptake. To take advantage of the radiotoxicity of [125I]-C8 against cervical cancer cells other strategies need to be studied, based namely on alternative nanodelivery carriers and/or intratumoral injection approaches.

Five-year evaluation of Anal Cancer Screening Program in Men Who Have Sex With Men with HIV at Two Academic Center Clinics.

Guidelines recommend annual anal cytology-based squamous cell carcinoma of anus (SCCA) screening for men who have sex with men (MSM) with HIV aged ≥35 years (eligible population). Recommended threshold for high resolution anoscopy (HRA) depends on its availability: low-threshold (any abnormal cytology) if availability is high, and high-threshold (High-Grade Squamous Intraepithelial Lesion (HSIL) on cytology) if availability is low. Retrospective chart review (2018-2022) at academic HIV clinics. We evaluate (i) 5-year uptake of cytology based SCCA screening in eligible population; (ii) estimate HSIL detection rate based on our current low-threshold criteria, and if high-threshold criteria were used for HRA referral. Of 432 eligible individuals, only 219 (50.7%) had at least one, and only 113 (26%) had >1 SCCA screening tests in a median followup of 4 years. N=74 (17.1%) of individuals had at least one abnormal anal cytology during follow-up, of which 56 (75.6%) received HRA. Increasing age (≥57 years) and history of smoking negatively correlated with ever receiving screening. Anal cytology (365 tests in 206 individuals) showed: 17.5% 'unsatisfactory', and 26.8% with any abnormal cytology (zero with HSIL) triggering HRA referral. Only 34 individuals (7.8% of screening eligible) were ever detected with HSIL. Strictly using high-threshold criterion for HRA referral would have led to no HRA or HSIL detection. We noted poor uptake of screening over time, particularly in older age groups. Importantly, anal cytology performed poorly as a triage test for HRA referral: high rates of 'unsatisfactory' samples and low sensitivity for detecting HSIL.

Training physicians in motivational communication: An integrated knowledge transfer study protocol.

While behavior change counseling (BCC) targeting health risk behaviors has shown efficacy for improving patient health outcomes, barriers to knowledge translation have resulted in poor uptake among health care providers (HCPs). This article outlines the development of a new BCC training framework for HCPs, from inception to readiness for efficacy testing. It provides an example of integrated knowledge translation (iKT) used in alignment with the obesity-related behavioral intervention trials model. (a) A modified Delphi process identified essential BCC skills for HCPs; (b) a survey assessed HCP attitudes and training needs; (c) an online competency assessment tool was developed using iKT mixed methods; (d) a training program was developed and refined using a logic model; and (e) the program was optimized using iterative rounds of participant feedback. A future proof-of-concept trial (f) will determine the program's readiness for full efficacy testing. A Delphi panel (n = 46) identified 11 core BCC competencies for HCPs, defining "motivational communication." The HCP survey (n = 80) showed willingness to devote 4 hr to introductory training in BCC. The Motivational Communication Competency Assessment Test (MC-CAT: an online, interactive evaluation tool) and a motivational communication training program (MOTIVATOR: accredited for continuing education by the Royal College of Physicians and Surgeons of Canada) were collaboratively developed with knowledge users. The optimization process (n = 11) provided key feedback, with minor changes being made to the program. In developing a new BCC framework, obstacles to BCC implementation were addressed through an iterative iKT process. This should improve eventual intervention uptake. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Targeted NAD+ repletion via biomimetic nanoparticle enables simultaneous management of intimal hyperplasia and accelerated re-endothelialization: A proof-of-concept study toward next-generation of endothelium-protective, anti-restenotic therapy

Endovascular interventions often fail due to restenosis, primarily caused by smooth muscle cell (SMC) proliferation, leading to intimal hyperplasia (IH). Current strategies to prevent restenosis are far from perfect and impose significant collateral damage on the fragile endothelial cell (EC), causing profound thrombotic risks. Nicotinamide adenine dinucleotide (NAD+) is a co-enzyme and signaling substrate implicated in redox and metabolic homeostasis, with a pleiotropic role in protecting against cardiovascular diseases. However, a functional link between NAD+ repletion and the delicate duo of IH and EC regeneration has yet to be established. NAD+ repletion has been historically challenging due to its poor cellular uptake and low bioavailability. We have recently invented the first nanocarrier that enables direct intracellular delivery of NAD+ in vivo. Combining the merits of this prototypic NAD+-loaded calcium phosphate (CaP) nanoparticle (NP) and biomimetic surface functionalization, we created a biomimetic P-NAD+-NP with platelet membrane coating, which enabled an injectable modality that targets IH with excellent biocompatibility. Using human cell primary culture, we demonstrated the benefits of NP-assisted NAD+ repletion in selectively inhibiting the excessive proliferation of aortic SMC, while differentially protecting aortic EC from apoptosis. Moreover, in a rat balloon angioplasty model, a single-dose treatment with intravenously injected P-NAD+-NP immediately post angioplasty not only mitigated IH, but also accelerated the regeneration of EC (re-endothelialization) in vivo in comparison to control groups (i.e., saline, free NAD+ solution, empty CaP-NP). Collectively, our current study provides proof-of-concept evidence supporting the role of targeted NAD+ repletion nanotherapy in managing restenosis and improving reendothelialization.

Implementation of a bundle to improve diagnosis in hospitalized patients: lessons learned.

The inpatient setting is a challenging clinical environment where systems and situational factors predispose clinicians to making diagnostic errors. Environmental complexities limit trialing of interventions to improve diagnostic error in active inpatient clinical settings. Informed by prior work, we piloted a multi-component intervention designed to reduce diagnostic error to understand its feasibility and uptake. From September 2018 to June 2019, we conducted a prospective, pre-test/post-test pilot study of hospital medicine physicians during admitting shifts at a tertiary-care, academic medical center. Optional intervention components included use of dedicated workspaces, privacy barriers, noise cancelling headphones, application-based breathing exercises, a differential diagnosis expander application, anda checklist to enable a diagnostic pause. Participants rated their confidence in patient diagnoses and completed a survey on intervention component use. Data on provider resource utilization and patient diagnoses were collected, and qualitative interviews were held with a subset of participants in order to better understand experience with the intervention. Data from 37 physicians and 160 patients were included. No intervention component was utilized by more than 50 % of providers, and no differences were noted in diagnostic confidence or number of diagnoses documented pre-vs. post-intervention. Lab utilization increased, but there were no other differences in resource utilization during the intervention. Qualitative feedback highlighted workflow integration challenges, among others, for poor intervention uptake. Our pilot study demonstrated poor feasibility and uptake of an intervention designed to reduce diagnostic error. This study highlights the unique challenges of implementing solutions within busy clinical environments.

Cipaglucosidase alfa plus miglustat: linking mechanism of action to clinical outcomes in late-onset Pompe disease.

Enzyme replacement therapy (ERT) is the only approved disease-modifying treatment modality for Pompe disease, a rare, inherited metabolic disorder caused by a deficiency in the acid α-glucosidase (GAA) enzyme that catabolizes lysosomal glycogen. First-generation recombinant human GAA (rhGAA) ERT (alglucosidase alfa) can slow the progressive muscle degeneration characteristic of the disease. Still, most patients experience diminished efficacy over time, possibly because of poor uptake into target tissues. Next-generation ERTs aim to address this problem by increasing bis-phosphorylated high mannose (bis-M6P) N-glycans on rhGAA as these moieties have sufficiently high receptor binding affinity at the resultant low interstitial enzyme concentrations after dosing to drive uptake by the cation-independent mannose 6-phosphate receptor on target cells. However, some approaches introduce bis-M6P onto rhGAA via non-natural linkages that cannot be hydrolyzed by natural human enzymes and thus inhibit the endolysosomal glycan trimming necessary for complete enzyme activation after cell uptake. Furthermore, all rhGAA ERTs face potential inactivation during intravenous delivery (and subsequent non-productive clearance) as GAA is an acid hydrolase that is rapidly denatured in the near-neutral pH of the blood. One new therapy, cipaglucosidase alfa plus miglustat, is hypothesized to address these challenges by combining an enzyme enriched with naturally occurring bis-M6P N-glycans with a small-molecule stabilizer. Here, we investigate this hypothesis by analyzing published and new data related to the mechanism of action of the enzyme and stabilizer molecule. Based on an extensive collection of in vitro, preclinical, and clinical data, we conclude that cipaglucosidase alfa plus miglustat successfully addresses each of these challenges to offer meaningful advantages in terms of pharmacokinetic exposure, target-cell uptake, endolysosomal processing, and clinical benefit.

Is there dietary macronutrient malabsorption in children with environmental enteropathy?

Assessing the digestive and absorptive capacity of the gastro-intestinal tract (GIT) using minimally- or non-invasive methods, particularly in children, has been difficult owing to the complex physiology and variability in functional measurements. However, measuring GIT function is increasingly important with the emerging relevance of childhood environmental enteropathy (EE) as a mediating factor in linear growth faltering, severe acute malnutrition, poor oral vaccine uptake and impaired cognition. In EE, sub-optimal nutrient digestion and absorption (malabsorption) forms the critical link to the conditions mentioned above. The present narrative review discusses probable mechanisms that can cause malabsorption of macronutrients, along with mechanistic and experimental evidence, in children (if not, in adults) with EE. The strengths and limitations of the human experimental studies are examined in relation to a battery of existing and potential tests that are used to measure malabsorption. From the available studies conducted in children, lactose and fat malabsorption are more likely to occur in EE. Breath tests (non-invasive) measuring carbohydrate (13C-starch/sucrose/lactose), fat (13C-mixed triglyceride) and dipeptide (benzoyl-L-tyrosyl-L-1-13C-alanine) malabsorption with modifications to the existing protocols seem suitable for use in children with EE. Future research should focus on understanding the degree of macronutrient malabsorption using these tests, in different settings, and link them to functional outcomes (such as growth, muscle strength, cognition).

Peptide-Oligonucleotide Conjugation: Chemistry and Therapeutic Applications.

Oligonucleotides have been identified as powerful therapeutics for treating genetic disorders and diseases related to epigenetic factors such as metabolic and immunological dysfunctions. However, they face certain obstacles in terms of limited delivery to tissues and poor cellular uptake due to their large size and often highly charged nature. Peptide-oligonucleotide conjugation is an extensively utilized approach for addressing the challenges associated with oligonucleotide-based therapeutics by improving their delivery, cellular uptake and bioavailability, consequently enhancing their overall therapeutic efficiency. In this review, we present an overview of the conjugation of oligonucleotides to peptides, covering the different strategies associated with the synthesis of peptide-oligonucleotide conjugates (POC), the commonly used peptides employed to generate POCs, with the aim to develop oligonucleotides with favourable pharmacokinetic (PK) or pharmacodynamic (PD) properties for therapeutic applications. The advantages and drawbacks of the synthetic methods and applications of POCs are also described.

Heteroduplex oligonucleotide technology boosts oligonucleotide splice switching activity of morpholino oligomers in a Duchenne muscular dystrophy mouse model

The approval of splice-switching oligonucleotides with phosphorodiamidate morpholino oligomers (PMOs) for treating Duchenne muscular dystrophy (DMD) has advanced the field of oligonucleotide therapy. Despite this progress, PMOs encounter challenges such as poor tissue uptake, particularly in the heart, diaphragm, and central nervous system (CNS), thereby affecting patient’s prognosis and quality of life. To address these limitations, we have developed a PMOs-based heteroduplex oligonucleotide (HDO) technology. This innovation involves a lipid-ligand-conjugated complementary strand hybridized with PMOs, significantly enhancing delivery to key tissues in mdx mice, normalizing motor functions, muscle pathology, and serum creatine kinase by restoring internal deleted dystrophin expression. Additionally, PMOs-based HDOs normalized cardiac and CNS abnormalities without adverse effects. Our technology increases serum albumin binding to PMOs and improves blood retention and cellular uptake. Here we show that PMOs-based HDOs address the limitations in oligonucleotide therapy for DMD and offer a promising approach for diseases amenable to exon-skipping therapy.

WP6.12 - What the bleep? Have we finally found a solution to the bleep system?: Exploring the efficacy of a WhatsApp-style messaging system as an alternative to traditional bleeps in the healthcare setting

Abstract Aims Traditionally, bleeps have been integral to the role of a doctor. A pre-pandemic study estimated that more than 10% of the world’s bleeps are currently being used by the NHS. However, in response to the 2021 directive by the health secretary to phase out bleeps within NHS England, new approaches to communication in healthcare are being implemented. One of these is Alertive, a WhatsApp-style messaging system. This study utilises a quality improvement approach to determine the efficacy of Alertive in conveying messages as a replacement for bleeps, and to investigate the reasons behind its perceived poor uptake. Methods A ten-day evaluation of the uptake of 15 distinct Alertive roles within the surgical department, accompanied by a satisfaction survey circulated among departmental juniors. Results The survey findings revealed a prevailing consensus among users endorsing the efficacy and superiority of Alertive as a concept over the previous bleep system. However, user-reported constraints related to functionality and application logistics. These have been identified as sources of frustration and thereby impeding the broader utilisation and efficacy of Alertive. Conclusion Effective multi-disciplinary communication is imperative in a hospital setting. While Alertive presents a potential alternative to traditional bleeps, challenges such as poor role uptake and communication appropriateness persist and represent significant barriers to full integration and staff satisfaction. Role uptake is variable with some surgical teams having better compliance than others. While users report that the concept of Alertive is beneficial, no single communication system has been identified as being superior, emphasising the ongoing need for solutions in healthcare communication.

Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores

In vitro screening of gallium-68(68Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([68Ga]Ga-ENT), considering different experimental factors. Compared with other reporting methods of uptake, ‘% Added dose/109 CFU/mL (% AD/109 CFU/mL),’ considering the total viable count, showed a better comparison among microbial species. Later, in vitro screening with [68Ga]Ga-desferrioxamine B (DFO-B) showed high uptake by Staphylococcus aureus and S. epidermidis; moderate uptake by Pseudomonas aeruginosa; poor uptake by E. coli, Candida albicans, and Aspergillus fumigatus; and no uptake by Enterococcus faecalis and C. glabrata. Except for S. epidermidis, [68Ga]Ga-DFO-B did not reduce the cell viability.

Exosomal Delivery Enhances the Antiproliferative Effects of Acid-Hydrolyzed Apiaceae Spice Extracts in Breast Cancer Cells.

Breast cancer remains a leading cause of death worldwide. The Apiaceae plant family includes many culinary spices that have been shown to have medicinal properties. Many phytochemicals exhibit potent bioactivities but often suffer from poor uptake and oral bioavailability. Bovine milk and colostrum exosomes are a compelling drug delivery platform that could address this issue; these natural nanoparticles can be loaded with hydrophilic and lipophilic small molecules and biologics, resulting in lower doses needed to inhibit cancer growth. Ethanolic extracts of eight Apiaceae spices were examined for phytochemical content and antiproliferative potential. Acid hydrolysis (AH) was employed to remove glycosides, asses its impacts on extract efficacy, and evaluate its effects on exosome loading and subsequent formulation efficacy. Antiproliferative activity was assessed through MTT assays on T-47D, MDA-MB-231, and BT-474 breast cancer cells; all extracts exhibited broad antiproliferative activity. AH enhanced the bioactivity of cumin, caraway, and fennel in T-47D cells. Celery, cumin, anise, and ajwain showed the highest activity and were assayed in exosomal formulations, which resulted in reduced doses required to inhibit cellular proliferation for all extracts except AH-cumin. Apiaceae spice extracts demonstrated antiproliferative activities that can be improved with AH and further enhanced with exosomal delivery.

Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications

Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures’ poor tumor uptake. To address this bottleneck, it is appealing to develop injectable in situ forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable in situ forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol–gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol–gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable in situ forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO3), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), in situ gelation capacity and cytocompatibility (viability > 73 %). As importantly, the dual-crosslinking improved the hydrogel’s porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells’ viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of S. aureus and E. coli to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.

Moving an exercise referral scheme to remote delivery during the Covid-19 pandemic: an observational study examining the impact on uptake, adherence, and costs

BackgroundExercise Referral Schemes (ERSs) have been implemented across Western nations to stimulate an increase in adult physical activity but evidence of their effectiveness and cost-effectiveness is equivocal. Poor ERS uptake and adherence can have a negative impact on effectiveness and cost-effectiveness and, if patterned by socio-demographic factors, can also introduce or widen health inequalities. Different modes of ERS delivery have the potential to reduce costs and enhance uptake and adherence. The primary aim of this study was to examine the effect of different programmes of ERS delivery on scheme uptake and adherence. Secondary aims were to examine the effect of socio-demographic factors on scheme uptake and adherence, and the impact of delivery mode on the expected resource and corresponding costs of delivering core parts of the programme.MethodsThis was an observational cohort study with cost analysis. Routine monitoring data covering a three-year period (2019–2021) from one large UK ERS (number of patients = 28,917) were analysed. During this period three different programmes of delivery were operated in succession: standard (all sessions delivered face-to-face at a designated physical location), hybrid (sessions initially delivered face-to-face and then switched to remote delivery in response to the Covid-19 pandemic), and modified (sessions delivered face-to-face, remotely, or a combination of the two, as determined on a case-by-case basis according to Covid-19 risk and personal preferences). Multi-level binary logistic and linear regression were performed to examine the effect of programme of delivery and socio-demographic characteristics on uptake and adherence. Cost data were sourced from regional-level coordinators and through NERS audits supplied by national-level NERS managers and summarised using descriptive statistics.ResultsThere was no effect of programme of delivery on scheme uptake. In comparison to those on the standard programme (who attended a mean of 23.1 exercise sessions) those on the modified programme had higher adherence (mean attendance of 25.7 sessions) while those on the hybrid programme had lower adherence (mean attendance of 19.4 sessions). Being older, or coming from an area of lower deprivation, increased the likelihood of uptake and adherence. Being female increased the chance of uptake but was associated with lower adherence. Patients referred to the programme from secondary care were more likely to take up the programme than those referred from primary care for prevention purposes, however their attendance at exercise sessions was lower. The estimated cost per person for face-to-face delivery of a typical 16-week cycle of the scheme was £65.42. The same cycle of the scheme delivered virtually (outside of a pandemic context) was estimated to cost £201.71 per person.ConclusionsThis study contributes new evidence concerning the effect of programme of delivery on ERS uptake and adherence and strengthens existing evidence concerning the effect of socio-economic factors. The findings direct the attention of ERS providers towards specific patient sub-groups who, if inequalities are to be addressed, require additional intervention to support uptake and adherence. At a time when providers may be considering alternative programmes of delivery, these findings challenge expectations that implementing virtual delivery will necessarily lead to cost savings.

Side-chain vertical imidazole backbone enhances phosphoric acid uptake in Poly(2,5-benzimidazole) membranes for high-temperature PEMFCs

PA-doped polybenzimidazole membranes dominate high-temperature proton exchange membranes (HT-PEMs), but the current membranes have poor PA uptake ability, which directly affects the operational efficiency and stability of fuel cells. In this work, it is proposed that a series of grafted polybenzimidazole membranes containing benzimidazole side chains were successfully prepared by grafting 2-chloromethyl benzimidazole to the backbone of poly (2,5-benzimidazole) (ABPBI) via nucleophilic substitution reaction. All these membranes exhibited excellent mechanical properties, oxidative stability, and thermal stability. The introduction of benzimidazole side chains not only increased the free volume of the membranes to store more PA but also added additional basic sites to form hydrogen bonds with PA molecules and constructed a dense hydrogen bonding network, which greatly enhanced the PA uptake of the membranes and accelerated the proton conduction to reduce the activation energy. The proton conductivity of the PA-doped g-ABPBI-50% membrane reached 0.122 S cm−1 at 180 °C under humidity-free conditions, while the peak power density of the PA-doped g-ABPBI-30% membrane was as high as 0.372 W cm−2 at 160 °C, which was 1.75 times higher than that of the pure ABPBI membrane. These results highlight the potential of this grafted membrane for high-temperature proton exchange membrane fuel cells (HT-PEMFCs) applications.

Talking About Things Important to Me: Mental Health Consumers' Experiences of Consumer-Rated Measures.

Since 2002, National Outcomes and Casemix Collection of clinician-rated and consumer-rated outcome measures has become part of routine care within Australian clinical mental health services, aiming to ensure that services understand, improve and are accountable for effectiveness of treatment and care provision. Consumer-rated outcome measures, implemented well, support basic human rights of consumers to be asked, heard and included equally in their own care. However, their use has lagged due to clinician inertia, uncertainty about their value to clinical care, assumptions about consumers' capacity to complete the measures and organisational cultural issues that have hampered more holistic assessment, consumer inclusion and care collaboration. Much is known about negative, largely tokenistic use of such measures, poor uptake and dominance of clinical approaches to measurement that privilege clinical expertise; however, little is known about consumers' positive experiences of using consumer-rated measures, Therefore, our aims were as follows: to seek the views and experiences of mental health consumers of using consumer-rated measures in their encounters with clinicians; to understand better whether there were benefits (and if so what) of consumer-rated measures being used in routine mental health practice; to understand how feedback on the use of consumer-rated measures can inform training for mental health staff; and to promote their wider use within mental health services. In-depth interviews conducted with 10 Australian mental health consumers used interview questions co-designed with lived experience and clinical advocates. Descriptive thematic analyses produced four themes emphasising consumers' preferences for completing the measures, the importance of explaining their purpose, how the process validated their feelings and was an opportunity for self-reflection, sense-making, trust-building, and transparency in the encounter and empowerment. This research offers recommendations about the value of effective implementation of consumer-rated measures.

Characterizing and Tailoring the Substrate Profile of a γ-Glutamyltransferase Variant.

Xenobiology is an emerging field that focuses on the extension and redesign of biological systems through the use of laboratory-derived xenomolecules, which are molecules that are new to the metabolism of the cell. Despite the enormous potential of using xenomolecules in living organisms, most noncanonical building blocks still need to be supplied externally, and often poor uptake into cells limits wider applicability. To improve the cytosolic availability of noncanonical molecules, a synthetic transport system based on portage transport was developed, in which molecules of interest "cargo" are linked to a synthetic transport vector that enables piggyback transport through the alkylsulfonate transporter (SsuABC) of Escherichia coli. Upon cytosolic delivery, the vector-cargo conjugate is enzymatically cleaved by GGTxe, leading to the release of the cargo molecule. To deepen our understanding of the synthetic transport system, we focused on the characterization and further development of the enzymatic cargo release step. Hence, the substrate scope of GGTxe was characterized using a library of structurally diverse vector-cargo conjugates and MS/MS-based quantification of hydrolysis products in a kinetic manner. The resulting substrate tolerance characterization revealed that vector-amino acid conjugates were significantly unfavored. To overcome this shortcoming, a selection system based on metabolic auxotrophy complementation and directed evolution of GGTxe was established. In a directed evolution campaign, we improved the enzymatic activity of GGTxe for vector-amino acid conjugates and revealed the importance of residue D386 in the cargo unloading step.