PROACT 2.0: A new open-source tool to improve patient-doctor communication in clinical trials.

The use of Digital Healthcare Products is leading to significant improvements in clinical practice. Herein, we discuss the development of PROACT 2.0 (Patient Reported Opinions About Clinical Tolerability v2.0), a novel open-source mobile and web application developed at Fondazione IRCCS Istituto Nazionale Tumori in Milan. It was developed in collaboration with The Christie, Manchester, in the context of work package 2 of the UpSMART Accelerator project, involving a consortium of referral cancer centers from the UK, Spain and Italy. PROACT 2.0 enhances communication between patients and healthcare providers in cancer clinical trials, allowing patients to report adverse events and side effects, and healthcare teams to collect valuable patient-reported outcome measures for treatment management. PROACT 2.0 supports text, audio, and video messaging, offering a secure, non-urgent communication channel that integrates with, or replaces, traditional methods. Its user-friendly and multilingual interface provides a new route for patient engagement and streamlines the handling of logistical information. Positive feedback from initial testing warrants future enhancements for broader applicability in cancer research and treatment.

Spatial and Temporal Detection of Ions Ejected from Coulomb Crystals.

Coulomb crystals have proven to be powerful and versatile tools for the study of ion-molecule reactions under cold and controlled conditions. Reactions in Coulomb crystals are typically monitored through a combination of in situ fluorescence imaging of the laser-cooled ions and destructive time-of-flight mass spectrometry measurements of the ejected ions. However, neither of these techniques is able to provide direct structural information on the positions of nonfluorescing "dark" ions within the crystal. In this work, structural information is obtained using a phosphor screen and a microchannel plate detector in conjunction with a Timepix3 camera. The Timepix3 camera simultaneously records the spatial and temporal distribution of all ions that strike the phosphor screen detector following crystal ejection at a selected reaction time. A direct comparison can be made between the observed Timepix3 ion distributions and the distributions established from SIMION simulations of the ion trajectories through the apparatus and onto the detector. Quantitative agreement is found between the measured Timepix3 signal and the properties of Coulomb crystals assigned using fluorescence imaging─independently confirming that the positions and numbers of nonfluorescing ions within Coulomb crystals can be accurately determined using molecular dynamics simulations. It is anticipated that the combination of high-resolution spatial and temporal data will facilitate new measurements of the ion properties within Coulomb crystals.

The prevalence of developmental defects of enamel in a cohort of adults with cystic fibrosis - A cross sectional study.

OBJECTIVES: Cystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. METHODS: A cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland. RESULTS: 64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. CONCLUSION: In this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings. CLINICAL SIGNIFICANCE: Clinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

The Application of High-Resolution, Embedded Fibre Optic (FO) Sensing for Large-Diameter Composite Steel/Plastic Pipeline Performance under Dynamic Transport Loads.

Distributed optical fibre sensing (DOFS)-based strain measurement systems are now routinely deployed across infrastructure health monitoring applications. However, there are still practical performance and measurement issues associated with the fibre's attachment method, particularly with thermoplastic pipeline materials (e.g., high-density polyethylene, HDPE) and adhesive affixment methods. In this paper, we introduce a new optical fibre installation method that utilises a hot-weld encapsulation approach that fully embeds the fibre onto the pipeline's plastic surface. We describe the development, application and benefits of the new embedment approach (as compared to adhesive methods) and illustrate its practical performance via a full-scale, real-world, dynamic loading trial undertaken on a 1.8 m diameter, 6.4 m long stormwater pipeline structure constructed from composite spiral-wound, steel-reinforced, HDPE pipe. The optical frequency domain reflectometry (OFDR)-based strain results show how the new method improves strain transference and dynamic measurement performance and how the data can be easily interpreted, in a practical context, without the need for complex strain transfer functions. Through the different performance tests, based on UK rail-road network transport loading conditions, we also show how centimetre- to metre-scale strain variations can be clearly resolved at the frequencies and levels consistent with transport- and construction-based, buried infrastructure loading scenarios.

Periodontal disease prevalence and oral hygiene status of adults with cystic fibrosis: A case-control study.

AIM: To investigate the prevalence of gingivitis and periodontitis, and the oral hygiene status of adults with cystic fibrosis (CF) in the Republic of Ireland. MATERIALS AND METHODS: A case-control study in the form of a clinical examination of 92 adults with a diagnosis of CF was carried out in the adult CF unit in Cork University Hospital. A 40-item questionnaire was used to capture socio-demographic variables and medical and dental information. Two calibrated examiners carried out a periodontal assessment on participants, using the WHO-recommended CPI-modified index, and oral hygiene status was measured using the Greene-Vermillion index. The results were compared with a population-based control group of similar socio-demographic profile. RESULTS: Oral hygiene levels (plaque and calculus) were significantly worse in people with CF, with a median plaque index of 0.83 (interquartile range [IQR] 0.333-1.542) in the CF group compared with 0.5 (IQR 0.167-0.667) in the non-CF group. Calculus index in the CF group was 0.33 (IQR 0.17-0.83) compared with 0.33 (IQR 0.125-0.33) in the non-CF group. However, periodontal disease levels were significantly lower in the CF group. Gingivitis (bleeding on probing ≥ 10% sites) was seen in 67.4% of the CF group, compared with 83.7% of the non-CF group, OR 0.365 (95% confidence interval [CI] 0.181-0.736), relative risk (RR) 0.779 (95% CI 0.655-0.928). Mild periodontitis (periodontal probing depth [PPD] < 5 mm) was seen in 15.2% of the CF group, compared with 31.5% of the non-CF group, OR 0.390 (CI 0.190-0.800), RR 0.483 (95% CI 0.273-0.852). Severe periodontitis (PPD ≥ 6 mm) was seen in 0% of the CF group, compared with 9.8% of the non-CF group. There was a tendency, albeit non-significant, towards reduced periodontitis in PWCF who regularly took antibiotics, particularly azithromycin. CONCLUSIONS: In this study, adults with CF had poor oral hygiene practices, with high levels of plaque and calculus. Despite this finding, adults with CF had lower levels of clinical gingivitis and periodontitis than seen in a non-CF control group. Further study is required to examine the causes of this phenomenon.

Improvement in Lung Clearance Index and Chest Computed Tomography Scores with Elexacaftor/Tezacaftor/Ivacaftor Treatment in People with Cystic Fibrosis Aged 12 Years and Older - The RECOVER Trial.

Rationale: Clinical trials have shown that use of elexacaftor/tezacaftor/ivacaftor (ETI) is associated with improvements in sweat chloride, pulmonary function, nutrition, and quality of life in people with cystic fibrosis (CF). Little is known about the impact of ETI on ventilation inhomogeneity and lung structure. Objectives: RECOVER is a real-world study designed to measure the impact of ETI in people with CF. The primary endpoints were lung clearance (lung clearance index; LCI2.5) and FEV1. Secondary endpoints included spirometry-controlled chest computed tomography (CT) scores. Methods: The study was conducted in seven sites in Ireland and the United Kingdom. Participants ages 12 years and older who were homozygous for the F508del mutation (F508del/F508del) or heterozygous for F508del and a minimum-function mutation (F508del/MF) were recruited before starting ETI and were followed up over 12 months. LCI2.5 was measured using nitrogen multiple breath washout (MBW) at baseline and at 6 and 12 months. Spirometry was performed as per the criteria of the American Thoracic Society and the European Respiratory Society. Spirometry-controlled chest CT scans were performed at baseline and at 12 months. CT scans were scored using the Perth Rotterdam Annotated Grid Morphometric Analysis (PRAGMA) system. Other outcome measures include weight, height, Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R), and sweat chloride. Measurements and Main Results: One hundred seventeen people with CF ages 12 and older were recruited to the study. Significant improvements were seen in LCI scores (-2.5; 95% confidence interval [CI], -3.0, -2.0) and in the percents predicted for FEV1 (8.9; 95% CI, 7.0, 10.9), FVC (6.6; 95% CI, 4.9, 8.3), and forced expiratory flow between 25% and 75% of expired volume (12.4; 95% CI, 7.8, 17.0). Overall PRAGMA-CF scores reflecting airway disease improved significantly (-3.46; 95% CI, -5.23, -1.69). Scores for trapped air, mucus plugging, and bronchial wall thickening improved significantly, but bronchiectasis scores did not. Sweat chloride levels decreased in both F508del/F508del (-43.1; 95% CI, -47.4, -38.9) and F508del/MF (-42.8; 95% CI, -48.5, -37.2) groups. Scores on the Respiratory Domain of the CFQ-R improved by 14.2 points (95% CI, 11.3, 17.2). At 1 year, sweat chloride levels were significantly lower for the F508del/F508del group compared with scores for the F508del/MF group (33.93 vs. 53.36, P < 0.001). Conclusions: ETI is associated with substantial improvements in LCI2.5, spirometry, and PRAGMA-CF CT scores in people with CF ages 12 years and older. ETI led to improved nutrition and quality of life. People in the F508del/F508del group had significantly lower sweat chloride on ETI treatment compared with the F508del/MF group. Clinical trial registered with www.clinicaltrials.gov (NCT04602468).

Telehealth in Cystic Fibrosis. A systematic review incorporating a novel scoring system and expert weighting to identify a 'top 10 manuscripts' to inform future best practices implementation.

The ongoing development and integration of telehealth within CF care has been accelerated in response to the Covid-19 pandemic, with many centres publishing their experiences. Now, as the restrictions of the pandemic ease, the use of telehealth appears to be waning, with many centres returning to routine traditional face-to-face services. For most, telehealth is not integrated into clinical care models, and there is a lack of guidance on how to integrate such a service into clinical care. The aims of this systematic review were to first identify manuscripts which may inform best CF telehealth practices, and second, to analyse these finding to determine how the CF community may use telehealth to improve care for patients, families, and Multidisciplinary Teams into the future. To achieve this, the PRISMA review methodology was utilised, in combination with a modified novel scoring system that consolidates expert weighting from key CF stakeholders, allowing for the manuscripts to be placed in a hierarchy in accordance with their scientific robustness. From the 39 found manuscripts, the top ten are presented and further analysed. The top ten manuscripts are exemplars of where telehealth is used effectively within CF care at this time, and demonstrate specific use cases of its potential best practices. However, there is a lack of guidance for implementation and clinical decision making, which remains an area for improvement. Thus, it is suggested that further work explores and provides guidance for standardised implementation into CF clinical practice.

Isolation and Quarantine for Coronavirus Disease 2019 in the United States, 2020-2022.

BACKGROUND: Public health programs varied in ability to reach people with coronavirus disease 2019 (COVID-19) and their contacts to encourage separation from others. For both adult case patients with COVID-19 and their contacts, we estimated the impact of contact tracing activities on separation behaviors from January 2020 until March 2022. METHODS: We used a probability-based panel survey of a nationally representative sample to gather data for estimates and comparisons. RESULTS: An estimated 64 255 351 adults reported a positive severe acute respiratory syndrome coronavirus 2 test result; 79.6% isolated for ≥5 days, 60.2% isolated for ≥10 days, and 79.2% self-notified contacts. A total of, 24 057 139 (37.7%) completed a case investigation, and 46.2% of them reported contacts to health officials. More adults who completed a case investigation isolated than those who did not complete a case investigation (≥5 days, 82.6% vs 78.2%, respectively; ≥10 days, 69.8% vs 54.8%; both P < .05). A total of 84 946 636 adults were contacts of a COVID-19 case patient. Of these, 73.1% learned of their exposure directly from a case patient; 49.4% quarantined for ≥5 days, 18.7% quarantined for ≥14 days, and 13.5% completed a contact tracing call. More quarantined among those who completed a contact tracing call than among those who did not complete a tracing call (≥5 days, 61.2% vs 48.5%, respectively; ≥14 days, 25.2% vs 18.0%; both P < .05). CONCLUSIONS: Engagement in contact tracing was positively correlated with isolation and quarantine. However, most adults with COVID-19 isolated and self-notified contacts regardless of whether the public health workforce was able to reach them. Identifying and reaching contacts was challenging and limited the ability to promote quarantining, and testing.

Digital ECMT Cancer Trial Matching Tool: an Open Source Research Application to Support Oncologists in the Identification of Precision Medicine Clinical Trials.

PURPOSE: Matching patients with cancer to precision medicine clinical trials on the basis of their tumor genotype has the potential to improve outcomes for patients who have exhausted standard-of-care treatment options. However, the matching process presents a substantial challenge because of the number of clinical trials available. We describe a free, open source research tool designed to extract relevant trial information to support oncologists in the matching process, and we illustrate its utility with recent case studies of patients who were matched to trials using this tool. METHODS: Trial records are sourced from ClinicalTrials.gov and indexed using natural language processing techniques, including named entity recognition, term normalization, and relationship extraction. Relationships between trials and genetic alterations are assigned scores on the basis of a rule-based system. All data are updated daily. A user interface is provided via R Shiny app. RESULTS: An instance of the trial match tool, configured for UK clinical trials, is hosted by the digital Experimental Cancer Medicine Team (see link in Data Sharing Statement). Users select the relevant cancer type and genetic alteration(s). Matching studies are ranked according to the score assigned for the selected genetic alterations. Results may be downloaded and attached to the patient's health record if desired. The tool is currently being used to support the ongoing TARGET National study, which aims to match up to 6,000 patients to early phase clinical trials. We present three case studies that exemplify relationships between genetic alterations and studies. CONCLUSION: With increasing numbers of precision medicine treatments and as comprehensive molecular profiling of tumor samples becomes more common, decision support tools are likely to become increasingly important. This work represents an important step toward the development and wider implementation of such systems.

Patient attrition in Molecular Tumour Boards: a systematic review.

BACKGROUND: Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatment. METHODS: A literature review was performed to understand patient attrition within MTBs and barriers to patients receiving treatment. A total of 51 papers were reviewed spanning a 6-year period from 11 different countries. RESULTS: In total, 20% of patients received treatment through the MTB process. Of those that did not receive treatment, the main reasons were no mutations identified (27%), no actionable mutations (22%) and clinical deterioration (15%). However, data were often incomplete due to inconsistent reporting of MTBs with only 55% reporting on patients having no mutations, 55% reporting on the presence of actionable mutations with no treatment options and 59% reporting on clinical deterioration. DISCUSSION: As patient attrition in MTBs is an issue which is very rarely alluded to in reporting, more transparent reporting is needed to understand barriers to treatment and integration of new technologies is required to process increasing omic and treatment data.

A multi-site prospective, observational study of physiotherapist independent prescribing activity across musculoskeletal clinics in the United Kingdom.

OBJECTIVE: To establish how advanced practice physiotherapists in the UK working in the musculoskeletal specialty are utilising their independent non-medical prescribing skills. DESIGN: Multi-site, prospective, descriptive observational study. Ethics reference No: ERN_19-0994). METHOD: The study was conducted by seven advanced practitioners, across seven clinical sites representative of advanced musculoskeletal practice in the UK, between 1st October 2019-March 31, 2020. Advanced physiotherapy practitioner independent prescribers working in a variety of musculoskeletal specialty areas collected data across 5 contexts of musculoskeletal clinical service: first contact practice, primary care, community triage, secondary care orthopaedics, secondary care rheumatology and private practice. Quantitative data were analysed descriptively with qualitative data analysed/synthesised via thematic analysis. RESULTS: Prescribing activity data for n = 2470 patients were collected. Prescribing activity was highest for the treatment of nociceptive pain (51.3%) and inflammation (39.6%). Most prescribing activity occurred in the first 2-6 weeks (34.1%) following onset of condition. Medicines optimisation accounted for most of prescribing activity (18.1%), followed by over-the-counter medication recommendation (15.5%). De-prescribing accounted for 10.8% of all prescribing activity recorded. Qualitative data were synthesised into 4 themes: multimodal physiotherapeutic approach, joint decision making and patient choice, working with complexity, and legal and regulatory restriction. CONCLUSIONS: Physiotherapist independent prescribing was used within all health sectors in conjunction with advanced skills in musculoskeletal physiotherapy as part of a multimodal physiotherapeutic approach. Prescribing activity was dictated by the clinicians' clinical reasoning and use of joint decision-making. Prescribing activity for acute back and neuropathic radicular pain was limited secondary to recent reclassification of gabapentin and pregabalin.

Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital.

OBJECTIVES: COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19. DESIGN AND SETTING: This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England. PARTICIPANTS: Six hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent. RESULTS: The majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), and most were discharged within 1 week after admission (30/45, 67%). The highest risk patients, as determined by the 4C mortality score predictor, had high mortality (27/29, 93%), with most dying within 1 week after admission (22/29, 76%). Consistent with previous reports, most patients presented with high levels of C reactive protein (CRP) (67% of patients >50 mg/L), D-dimer (98%>upper limit of normal (ULN)), ferritin (65%>ULN), lactate dehydrogenase (90%>ULN) and low lymphocyte counts (81%

Wave comparisons of clinical characteristics and outcomes of COVID-19 admissions - Exploring the impact of treatment and strain dynamics.

OBJECTIVES: Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study. METHODS: This retrospective observational study reports patient characteristics, interventions and outcomes in COVID-19 patients from a UK teaching hospital; cohort 1, pre 16th June-2020 (pre-dexamethasone); cohort 2, 17th June to 30th November-2020 (post-dexamethasone, pre-VOC 202,012/01 as dominant strain); cohort 3, 1st December-2020 to 3rd March-2021 (during establishment of VOC202012/01 as the dominant strain). RESULTS: Dexamethasone treatment was more common in cohorts 2 and 3 (42.7% and 51.6%) compared with cohort 1 (2.5%). After adjusting for risk, odds of death within 28 days were 2-fold lower in cohort 2 vs 1 (OR:0.47,[0.27,0.79],p = 0.006). Mortality was higher cohort 3 vs 2 (20% vs 14%); but not significantly different to cohort 1 (OR: 0.86,[0.64, 1.15],p = 0.308). CONCLUSIONS: The real world finding of lower mortality following dexamethasone supports the published trial evidence and highlights ongoing need for research with introduction of new treatments and ongoing concern over new COVID-19 variants.

The systemic immunosuppressive effects of peripheral corticosteroid injections: A narrative review of the evidence in the context of COVID-19.

INTRODUCTION: Injected glucocorticoid's (corticosteroids) are commonly used in musculoskeletal practice. The current global COVID-19 pandemic has increased attention on the potential for locally injected corticosteroids to exert a systemic immunosuppressive effect and the implications this may have in relation to COVID-19 infection and vaccination. AIM: This narrative review summarises the evidence regarding the potential systemic immunosuppressive effects of peripheral corticosteroid injections in relation to the ongoing COVID-19 pandemic. METHOD: A narrative review was selected to allow inclusion of evidence related to a diverse range of topics relevant to this subject in order to provide the most comprehensive and clinically relevant guidance for clinicians. RESULTS/DISCUSSION: Current evidence demonstrates that cytotoxic, phagocytic and antigen presenting cells involved in both the innate and adaptive immune responses are suppressed for 48 h post-injection and messenger cytokines that are integral to immune function are suppressed for over 96 h post-injection. This potentially reduces an individual's ability to prevent viral infection, limit early viral replication, and delays activation of adaptive immune mechanisms (T and B lymphocytes) and subsequent viral clearance and elimination. The hypothalamic-pituitary-adrenal (HPA) axis can be suppressed for 2-4 weeks or longer following peripheral corticosteroid injections. The role of the HPA axis in immune function is not fully understood, however this could potentially indicate longer lasting immunosuppression. CONCLUSIONS: This review found evidence of suppression of immune cell numbers for the first 48 h post-injection, cytokines for over 96 h post-injection and HPA axis suppression lasting for 2-4 weeks or longer. There is currently no evidence that these physiological changes translate into a clinically meaningful increased risk of COVID-19 infection or related morbidity or mortality, but there is also no persuasive evidence that they do not. This review discusses the implications of the current evidence in relation to shared decision making, informed consent, risk management and COVID-19 vaccination to provide clinicians with a pragmatic guide to help navigate the current uncertainty regarding the potential immunosuppressive effects of peripheral corticosteroid injections.

Home-based Digital Assessments with Applied Sentiment & Emotion AI Capture Improved Quality-of-life in Asthma Patients.

With the rise of digital transformation in the pharmaceutical industry, digital therapeutics are being integrated in drug development clinical trials. In the TWINKLE study, information about asthmatic patients' disease control and quality-of-life (QoL) was measured by daily video recording, in conjunction with daily electronic questionnaires and home-based spirometry. From the video messages, sentiment and emotion AI was applied to detect subtle QoL changes in asthmatic patients after receiving treatments. Sentiment scores, derived from patients' daily messages via natural language processing, correlated strongly with metrics of lung functions and outcomes of electronic questionnaires. However, video-derived emotional analysis exhibited strong interpersonal variations and systematic biases, yet still showed utility in detecting QoL changes after personalized calibration and signal aggregation. Compared to traditional patient-reported outcomes, all three categories of digital measurements were able to detect significantly improved asthma control from patients who responded to treatments. The result provides insights into developing novel digital outcomes through the application of connected digital devices and advanced AI tailored to clinical settings.Clinical relevance- Digital outcomes involving connected digital devices and AI for sentiment/emotion analysis could capture subtle QoL changes reliably and earlier than hospital visits, reducing burden and improving disease management. Integrating digital therapeutics in asthma drug development trials may prove to be feasible and valuable.

DAF-16 and SMK-1 Contribute to Innate Immunity During Adulthood in Caenorhabditis elegans.

Aging is accompanied by a progressive decline in immune function termed "immunosenescence". Deficient surveillance coupled with the impaired function of immune cells compromises host defense in older animals. The dynamic activity of regulatory modules that control immunity appears to underlie age-dependent modifications to the immune system. In the roundworm Caenorhabditis elegans levels of PMK-1 p38 MAP kinase diminish over time, reducing the expression of immune effectors that clear bacterial pathogens. Along with the PMK-1 pathway, innate immunity in C. elegans is regulated by the insulin signaling pathway. Here we asked whether DAF-16, a Forkhead box (FOXO) transcription factor whose activity is inhibited by insulin signaling, plays a role in host defense later in life. While in younger C. elegans DAF-16 is inactive unless stimulated by environmental insults, we found that even in the absence of acute stress the transcriptional activity of DAF-16 increases in an age-dependent manner. Beginning in the reproductive phase of adulthood, DAF-16 upregulates a subset of its transcriptional targets, including genes required to kill ingested microbes. Accordingly, DAF-16 has little to no role in larval immunity, but functions specifically during adulthood to confer resistance to bacterial pathogens. We found that DAF-16-mediated immunity in adults requires SMK-1, a regulatory subunit of the PP4 protein phosphatase complex. Our data suggest that as the function of one branch of the innate immune system of C. elegans (PMK-1) declines over time, DAF-16-mediated immunity ramps up to become the predominant means of protecting adults from infection, thus reconfiguring immunity later in life.

Progress on the introduction of supervisory ward manager roles since the Francis report recommendations.

Recommendation 195 of the Francis report suggested that the introduction of supervisory ward managers into clinical practice could improve the quality of patient care in England. The Department of Health and NHS Commissioning Board's vision and strategy Compassion in Practice in 2012 restated the recommendation in action area four, with trusts required to publish progress. With the aim of identifying whether the lessons of the Francis report had been learned, a review of the published literature since 2012 retrieved only five articles on the subject, with many anecdotal accounts of its implementation in local trusts. The three subsequent update reports of Compassion in Practice stopped backing recommendation 195 and promoted black and ethnic minority leadership, a laudable initiative, but not a recommendation of the Francis report. The authors suggest recommendation 195 and Compassion in Practice's original action area four should be promoted again to ensure public safety and address the notion that lessons learned are less likely to be repeated.