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The creative research method "draw and write" has been used in health, social care and education research for several decades. A literature search of studies utilising this method was conducted during the planning stages of a study exploring primary school children's perceptions of infant feeding. A review of this literature noted a range of benefits of "draw and write" in enabling child participation. However, it also identified that the method has been used inconsistently and found that there are issues for researchers in relation to interpretation of creative work and analysis of data. As a result of this, an improvement on this method, entitled "draw, write and tell", was developed in an attempt to provide a more child-orientated and consistent approach to data collection, interpretation and analysis. This article identifies the issues relating to "draw and write" and describes the development and application of "draw, write and tell" as a case study, noting its limitations and benefits.

A 24-year-old male was admitted with progressive cervical hypesthesia, tetraparesis, dyspnea, and a history of craniofacial fracture. Spinal magnetic resonance imaging (MRI) showed brainstem edema extending to the thoracic spine with multiple prominent perimedullary vascular structures. Cerebral digital-substraction angiography revealed Barrow type A carotid-cavernous fistula. Total occlusion with preservation of internal carotid artery flow was achieved using 1 detachable balloon and 6 coils. Postoperatively, immediate respiratory recovery, gradual extremities strength improvement, and right abducens nerve palsy were found. One month follow-up cervical MRI showed good recovery of spinal cord edema and perimedullary veins.

Aims: It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs. Methods: The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome. Results: The SF-36 physical component summary mean at baseline was 30.9 (95% CI 29.7 to 32.0). At one month, it was unchanged (30.5; 95% CI 29.5 to 31.5; p = 0.447); it had improved statistically significantly at six months (35.5; 95% CI 34.2 to 36.7; p < 0.001) and at 12 months (37.9; 95% CI 36.4 to 39.3; p < 0.001). The SF-36 mental component summary mean at baseline was 42.5 (95% CI 40.8 to 44.2). At one month, it was unchanged (43.1; 95% CI 41.4 to 44.8; p = 0.458); it had improved statistically significantly at six months (47.1; 95% CI 45.4 to 48.7; p < 0.001) and at 12 months (46.7; 95% CI 45.0 to 48.5; p < 0.001). All mental subscales had improved by the end of the study, but mental health status remained compromised in comparison with the average USA population. Conclusion: BJIs considerably impact HRQoL, particularly mental health. Patients suffering from BJIs reported considerable limitations in their daily and social activities due to psychological problems. Impaired mental health may be explained by the chronic nature of BJIs, and therefore the mental wellbeing of these patients should be monitored closely. Cite this article: Bone Jt Open 2024;5(9):721–728.

Abstract Background Generating synthetic patient data is crucial for medical research, but common approaches build up on black-box models which do not allow for expert verification or intervention. We propose a highly available method which enables synthetic data generation from real patient records in a privacy preserving and compliant fashion, is interpretable and allows for expert intervention. Methods Our approach ties together two established tools in medical informatics, namely OMOP as a data standard for electronic health records and Synthea as a data synthetization method. For this study, data pipelines were built which extract data from OMOP, convert them into time series format, learn temporal rules by 2 statistical algorithms (Markov chain, TARM) and 3 algorithms of causal discovery (DYNOTEARS, J-PCMCI+, LiNGAM) and map the outputs into Synthea graphs. The graphs are evaluated quantitatively by their individual and relative complexity and qualitatively by medical experts. Results The algorithms were found to learn qualitatively and quantitatively different graph representations. Whereas the Markov chain results in extremely large graphs, TARM, DYNOTEARS, and J-PCMCI+ were found to reduce the data dimension during learning. The MultiGroupDirect LiNGAM algorithm was found to not be applicable to the problem statement at hand. Conclusion Only TARM and DYNOTEARS are practical algorithms for real-world data in this use case. As causal discovery is a method to debias purely statistical relationships, the gradient-based causal discovery algorithm DYNOTEARS was found to be most suitable.

Abstract Background The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes. Methods Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365. Results The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27–0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6–1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3–4.5) in the control group, p = 0.037. Conclusions Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial. Trial Registration ClinicalTrials.gov, NCT03262142, registration date 2017–08-25.

Background: Psoriasis is associated with high alcohol consumption, but the causality of this relationship is unclear. Objective: We aimed to use a Mendelian randomization approach to investigate the causal effects of alcohol on incident psoriasis. Methods: We included 102,655 adults from the prospective Copenhagen studies. All participants filled out a questionnaire on alcohol consumption, were physically examined, and had blood drawn for biochemical and genetic analyses. We created a genetic instrument based on the number of fast-metabolizing alleles in alcohol dehydrogenase 1B and alcohol dehydrogenase 1C, known to be associated with alcohol consumption, to test whether alcohol consumption was causally associated with psoriasis. Results: Observationally, we found an increased risk of incident psoriasis among individuals with high alcohol consumption compared to those with low alcohol consumption with a hazard ratio of 1.30 (95% confidence interval 1.05-1.60) in the fully adjusted model. Using genetic data to predict alcohol consumption to avoid confounding and reverse causation, we found no association between number of fast-metabolizing alleles and risk of psoriasis. Limitations: Alcohol consumption was self-reported and psoriasis was defined using the International Classification of Diseases 10th revision and 8th revision codes. Conclusion: Alcohol consumption is observationally but not causally associated with incident psoriasis.

ObjectivesTo assess diagnostic mycology capacity and available fungal diagnostic services of microbiology laboratories in eight tertiary hospitals in Nigeria and one in Ghana.MethodsOn-site audits were performed in the microbiology laboratories of nine tertiary hospitals using a structured observation checklist.ResultsA total of nine tertiary hospitals' laboratories in Nigeria and Ghana were assessed between June 2022 and December 2023. The majority of audited laboratories lacked basic infrastructure and materials needed for fungal diagnostic testing, with less than half of the labs having a dedicated mycology bench, space or room, 3/9 (33.3%), appropriate bench workflow 1/9 (11.1%), functional biosafety cabinet type two 2/9 (22.2%), dedicated incubators 3/9 (33.3%), standard operating procedures 1/9 (11.1%), mycology atlases 2/9 (22.2%). Trained laboratory personnel for mycology were also lacking with only one of the laboratories 1/9 (11.1%) observed to have a designated trained personnel for the mycology bench.ConclusionThe audit revealed deficits in basic infrastructure, material resources, dedicated human resources, and laboratory capacity to detect serious fungal infections.

In 2012, three members of staff were recruited by the University of Strathclyde to sit in a room and talk to students. That was the whole of the plan. That is not how this story ends. The talking was supposed to ‘help’ students to do things ‘right’. That is not what we spoke about. That year, the student-facing part of the Centre for Academic Practice and Learning Enhancement (CAPLE) established in 1987, which at its height consisted of six permanent academics with varied research interests within the, then emergent, field of Learning Development (LD), was replaced by a generic Study Skills Service, staffed by LD practitioners with a considerable collective experience and who shared a vision that was more critical and looked to a more authentically (learning) developmental approach (Asher, 2024). In so doing, the university had created a service model which we would spend the next nine years dismantling (or, to be more accurate, redeveloping). What follows is our story. The story of how the Learner Development Service (LDS) came into being, and how the spaces and places we have inhabited (both hostile and hospitable) have shaped our practices (Gravett et al., 2023) and how, in June 2022, we took up residency in a dedicated LDS Centre designed by us for us. To date, we have occupied three physical locations and been positioned under three different university services. These spaces and places have defined what we could do but they have also informed the design of our current physical, virtual and conceptual environment, as this paper details. This session highlighted the need for Learning Development practitioner resilience and perseverance in difficult circumstances. It foregrounds the usefulness of initiating, developing, and nurturing productive and mutually rewarding professional relationships with academic departments, course leaders and individual academics in order to advance the growth of Learning Development provision in institutions.

BackgroundClinical routine data derived from university hospitals hold immense value for health-related research on large cohorts. However, using secondary data for hypothesis testing necessitates adherence to scientific, legal (such as the General Data Protection Regulation, federal and state protection legislations), technical, and administrative requirements. This process is intricate, time-consuming, and susceptible to errors. ObjectiveThis study aims to develop a platform that enables clinicians to use current real-world data for testing research and evaluate advantages and limitations at a large university medical center (542,944 patients in 2022). MethodsWe identified requirements from clinical practitioners, conceptualized and implemented a platform based on the existing components, and assessed its applicability in clinical reality quantitatively and qualitatively. ResultsThe proposed platform was established at the University Medical Center Hamburg-Eppendorf and made 639 forms encompassing 10,629 data elements accessible to all resident scientists and clinicians. Every day, the number of patients rises, and parts of their electronic health records are made accessible through the platform. Qualitatively, we were able to conduct a retrospective analysis of Parkinson disease over 777 patients, where we provide additional evidence for a significantly higher proportion of action tremors in patients with rest tremors (340/777, 43.8%) compared with those without rest tremors (255/777, 32.8%), as determined by a chi-square test (P

La micropropagación de teca (Tectona grandis Linn F.) permite multiplicar plantas elites de forma asexual en ambientes controlados. Con el empleo de biorreactores económicos de inmersión temporal, innovación generada en el laboratorio de cultivo de tejidos de la Universidad Nacional Agraria, en Managua, Nicaragua, se realizó esta investigación con el objetivo de evaluar el efecto de reguladores del crecimiento en yemas apicales y axilares en las fases de multiplicación y enraizamiento. Este trabajo se desarrolló en tres fases posteriores a la obtención del material vegetal in vitro que corresponden a: 1) respuesta morfogénica de segmentos de tallos, 2) respuesta morfogénica a la densidad de siembra y 3) respuesta rizogénica de segmentos de tallos. Se demostró que, en la micropropagación de teca con yemas apicales individuales y segmentos de tallos con un entrenudo y sin yema apical, resultó mejor el promedio de número de hojas con la adición de 1.00 mg L-1 de 6-BAP y 0.10 mg L-1 de GA3, mientras que con yemas apicales con dos o tres entrenudos el promedio de número de hojas resultó superior en el medio de cultivo que contenía 0.50 mg L-1 de 6-BAP combinado con 0.05 o 0.10 mg L-1 de GA3. La densidad de siembra de 30 yemas apicales con dos entrenudos y densidad de 40 yemas apicales o axilares logra mayor número de hojas. Con yemas apicales y axilares con dos entrenudos, las variables longitud del tallo, número de hojas y número de raíces, presentan similar comportamiento con las adiciones de 0.25 mg L-1, 0.50 mg L-1 y 0.75 mg L-1 de ácido indol acético, además, la categoría de buen vigor se obtiene en mayor porcentaje (60 % - 70 %) con el uso de estas variantes de medio de cultivo.

Abstract Background Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). Methods PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. Results From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (

Abstract Background Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well‐being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. Methods We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. Results Fifty‐eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. Conclusions Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research.

RationaleLong-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA.MethodsRandomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months.ResultsA total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment.Clinical trial registration:ClinicalTrials.gov, NCT05563675.

BackgroundInterpretability and intuitive visualization facilitate medical knowledge generation through big data. In addition, robustness to high-dimensional and missing data is a requirement for statistical approaches in the medical domain. A method tailored to the needs of physicians must meet all the abovementioned criteria. ObjectiveThis study aims to develop an accessible tool for visual data exploration without the need for programming knowledge, adjusting complex parameterizations, or handling missing data. We sought to use statistical analysis using the setting of disease and control cohorts familiar to clinical researchers. We aimed to guide the user by identifying and highlighting data patterns associated with disease and reveal relations between attributes within the data set. MethodsWe introduce the attribute association graph, a novel graph structure designed for visual data exploration using robust statistical metrics. The nodes capture frequencies of participant attributes in disease and control cohorts as well as deviations between groups. The edges represent conditional relations between attributes. The graph is visualized using the Neo4j (Neo4j, Inc) data platform and can be interactively explored without the need for technical knowledge. Nodes with high deviations between cohorts and edges of noticeable conditional relationship are highlighted to guide the user during the exploration. The graph is accompanied by a dashboard visualizing variable distributions. For evaluation, we applied the graph and dashboard to the Hamburg City Health Study data set, a large cohort study conducted in the city of Hamburg, Germany. All data structures can be accessed freely by researchers, physicians, and patients. In addition, we developed a user test conducted with physicians incorporating the System Usability Scale, individual questions, and user tasks. ResultsWe evaluated the attribute association graph and dashboard through an exemplary data analysis of participants with a general cardiovascular disease in the Hamburg City Health Study data set. All results extracted from the graph structure and dashboard are in accordance with findings from the literature, except for unusually low cholesterol levels in participants with cardiovascular disease, which could be induced by medication. In addition, 95% CIs of Pearson correlation coefficients were calculated for all associations identified during the data analysis, confirming the results. In addition, a user test with 10 physicians assessing the usability of the proposed methods was conducted. A System Usability Scale score of 70.5% and average successful task completion of 81.4% were reported. ConclusionsThe proposed attribute association graph and dashboard enable intuitive visual data exploration. They are robust to high-dimensional as well as missing data and require no parameterization. The usability for clinicians was confirmed via a user test, and the validity of the statistical results was confirmed by associations known from literature and standard statistical inference.

IntroductionThis study aimed to investigate students' perceptions of the use of 3D-printed typodonts by implementing a questionnaire and evaluating the students' comparisons between extracted, commercial and 3D-printed teeth.MethodsEthical approval was obtained (QMER20.586/2021) and questionnaire feedback was collected anonymously using an online survey. A total of 143 fourth- and fifth-year dental students were approached to participate during pre-clinical courses focussing on root canal therapy. The tooth design was based on micro-CT data of an extracted maxillary central incisor and 3D-printed with haptically-similar materials produced in previous work. The questionnaire comprised 11 Likert-scale questions, four open-ended questions, two “yes” or “no” questions and three closed-ended questions.ResultsEighty questionnaires were returned. Overall, the feedback was favourable towards the 3D-printed typodonts compared to the commercial teeth. The biggest difference in responses was in Question 6 related to the realism of drilling the enamel when comparing 3D-printed teeth with commercial ones. Statistical analysis showed a significant difference (p

A right aortic arch with an isolated left innominate artery from the pulmonary artery is an exceedingly rare congenital cardiac malformation. We describe the management and complex surgical timing considerations in two such cases, successfully operated on day 4 and 7 months of age, including the use of cranial ultrasound as a helpful tool to guide decision-making. We also describe the first reported association of this defect with a 4q25 deletion encompassing the LEF1 gene.

Life satisfaction is one of the most ambigious concept to take a hold on. One’s degree of life satisfaction can differ from other person even though they have a realtively similliar life. This research studies people who play video games regularly (gamers) from the age of eighteen to fifty six. As one of the common trait or stereotipically seen that gamers have difficulty in social aspect of their lifes. Using Structural Equation Modeling (SEM), the research will try to confirm the relationship between anxiety and social phobia toward life satisfaction. The final model shows that anxiety and social phobia shows a significant negative affect towards life satisfaction of gamers.

(1) Background: For patients irradiated due to prostate cancer, monitoring of bladder volume (BV) is crucial for accuracy of radiation delivery and minimizing exposure to surrounding healthy tissues. Due to the limited imaging capabilities of the CyberKnife system, ultrasound imaging plays a vital role in the monitoring of bladder filling. (2) Methods: A study was carried out in 142 prostate cancer patients treated with the CyberKnife system. Bladder ultrasound (US) was performed before each RTH session to assess real BV (rBV). The double US assessment of rBV was performed by two independent operators or a single operator during 177 and 495 RTH sessions, respectively, giving, in total, 1344 BV assessments. (3) Results: The mean BV in the first and second US assessment was 214.7 mL and 218.1 mL, respectively, while the mean planning bladder volume (pBV) was 340.8 mL. A pBV was significantly higher than an rBV. The mean difference between the US and CT assessment of BV was the smallest in the 100–349 mL group and the largest in the group above 349 mL. The Passing–Bablok regression results confirmed the reliability of the ultrasound (US) measurements. (4) Conclusions: The introduction of US-based BV assessment in patients irradiated due to prostate cancer using CyberKnife seems to be a crucial element in controlling the reproducibility of the treatment plan and should be a standard procedure. The pBV should be within the range of 200–300 mL. The US examination prior to CT scanning for planning is recommended to ensure the optimal range of BV for CT.

Despite increasing research into men's experience of pregnancy and fatherhood, experiences of men whose partner is undergoing fetal screening and diagnosis have been less well-studied. This paper begins to fin a gap in the literature by identifying several potentially conflicting male roles in screening, diagnosis and subsequent decision-making. Drawing on a wider qualitative study in the UK of experiences of antenatal screening, it is suggested men may play inter-linked roles: as parents, bystanders, protectors/supporters, gatherers and guardians of fact, and deciders or enforcers. These may be roles they have chosen, or which are assigned to them intentionally or unintentionally by others (their female partner, health professionals). Men's status and feelings as fathers are sometimes overlooked or suppressed, or may conflict with their other roles, particularly when screening detects possible problems with the baby. The paper concludes by discussing these findings in the context of the wider literature on men and pregnancy. Keywords: Antenatal screening; Antenatal diagnosis; Men; Parents; Fathers; Abortion, induced

Introduction Management controversy and clinical equipoise exist in treatments of long bone fractures and traumatic hip dislocation in paediatric patients due to the lack of high-quality clinical evidence. This protocol describes the effort of a large prospective global multicentre cohort study (registry) aiming at providing quality data to assist evidence-based treatment decision-making.Methods and analysis Eligible paediatric patients (N=750–1000) with open physes suffering from proximal humerus fractures, distal humerus fractures, proximal radius fractures, forearm shaft fractures, traumatic hip dislocations, femoral neck fractures or tibial shaft fractures will be recruited over a period of 24–36 months. Hospitalisation and treatment details (including materials and implants) will be captured in a cloud-based, searchable database. Outcome measures include radiographic assessments, clinical outcomes (such as range of motion, limb length discrepancies and implant removal), patient-reported outcomes (Patient Reported Outcomes Of Fracture, Patient-Reported Outcomes Measurement Information System (PROMIS) and EuroQol-5D (EQ-5D-Y)) and adverse events.Aside from descriptive statistics on patient demographics, baseline characteristics, types of fractures and adverse event rates, research questions will be formulated based on data availability and quality. A statistical analysis plan will be prepared before the statistical analysis.Ethics and dissemination Ethics approval will be obtained before patients are enrolled at each participating site. Patient enrolment will follow an informed consent process approved by the responsible ethics committee. Peer-reviewed publication is planned to disseminate the study results.Trial registration number NCT04207892.

Multiplayer online video games are a multibillion-dollar industry, to which widespread cheating presents a significant threat. Game designers compromise on game security to meet demanding performance targets, but reduced security increases the risk of potential malicious exploitation. To mitigate this risk, game developers implement alternative security sensors. The alternative sensors themselves become a liability due to their intrusive and taxing nature. Online multiplayer games with real-time gameplay are known to be difficult to secure due to the cascading exponential nature of many-many relationships among the components involved. Behavior-based security sensor schemes, or referees (a trusted third party), could be a potential solution but require frameworks to obtain the game state information they need. We describe our Trust-Verify Game Protocol (TVGP), which is a sensor protocol intended for low-trust environments and designed to provide game state information to help support behavior-based cheat-sensing detection schemes. We argue TVGP is an effective solution for applying an independent trusted referee capability to trust-lacking subdomains and demands high-performance requirements. Our experimental results validate high efficiency and performance standards for TVGP. We identify and discuss the operational domain assumptions of the TVGP validation testing presented here.

Abstract Cell-based therapeutics are promising interventions to repair ischemic cardiac tissue. However, no single cell type has yet been found to be both specialized and versatile enough to heal the heart. The synergistic effects of two regenerative cell types including endothelial colony forming cells (ECFC) and first-trimester human umbilical cord perivascular cells (FTM HUCPVC) with endothelial cell and pericyte properties respectively, on angiogenic and regenerative properties were tested in a rat model of myocardial infarction (MI), in vitro tube formation and Matrigel plug assay. The combination of FTM HUCPVCs and ECFCs synergistically reduced fibrosis and cardiomyocyte apoptosis, while promoting favorable cardiac remodeling and contractility. These effects were in part mediated by ANGPT2, PDGF-β, and VEGF-C. PDGF-β signaling-dependent synergistic effects on angiogenesis were also observed in vitro and in vivo. FTM HUCPVCs and ECFCs represent a cell combination therapy for promoting and sustaining vascularization following ischemic cardiac injury.

We modelled ground deformation at Soufrière Hills Volcano (SHV), using data collected by the Montserrat Volcano Observatory from 2010–2019. We investigate the combined use of Electronic Distance Measuring (EDM) and Global Positioning System (GPS) to distinguish shallow from mid-crustal magmatic processes and their surface deformation profiles. Our results suggest that the EDM network responds predominantly to changes in the shallow magmatic system, whereas GPS records variation at mid-crustal levels. In addition, we show that the behaviour of the EDM network, and of the GPS site HERM, can be explained by underpressurisation in a shallow dyke conduit orientated NNW–SSE, while the mid-crustal system was still undergoing pressurisation. The modelled dyke may be responding to magma cooling and contraction associated with a previous intrusion. We find that geodetic monitoring coverage of multiple flanks within 1 km of the vent can improve our understanding of shallow magmatic system processes with asymmetric deformation fields.

Abstract Aberrant DNA methylation accompanies genetic alterations during oncogenesis and tumour homeostasis and contributes to the transcriptional deregulation of key signalling pathways in cancer. Despite increasing efforts in DNA methylation profiling of cancer patients, there is still a lack of epigenetic biomarkers to predict treatment efficacy. To address this, we analyse 721 cancer cell lines across 22 cancer types treated with 453 anti-cancer compounds. We systematically detect the predictive component of DNA methylation in the context of transcriptional and mutational patterns, i.e., in total 19 DNA methylation biomarkers across 17 drugs and five cancer types. DNA methylation constitutes drug sensitivity biomarkers by mediating the expression of proximal genes, thereby enhancing biological signals across multi-omics data modalities. Our method reproduces anticipated associations, and in addition, we find that the NEK9 promoter hypermethylation may confer sensitivity to the NEDD8-activating enzyme (NAE) inhibitor pevonedistat in melanoma through downregulation of NEK9. In summary, we envision that epigenomics will refine existing patient stratification, thus empowering the next generation of precision oncology.

Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.

Aims: To systematically review qualitative studies of patients with distal tibia or ankle fracture, and explore their experience of injury and recovery. Methods: We undertook a systematic review of qualitative studies. Five databases were searched from inception to 1 February 2022. All titles and abstracts were screened, and a subset were independently assessed. Methodological quality was appraised using the Critical Appraisal Skills Programme (CASP) checklist. The GRADE-CERQual checklist was used to assign confidence ratings. Thematic synthesis was used to analyze data with the identification of codes which were drawn together to form subthemes and then themes. Results: From 2,682 records, 15 studies were reviewed in full and four included in the review. A total of 72 patients were included across the four studies (47 female; mean age 50 years (17 to 80)). Methodological quality was high for all studies, and the GRADE-CERQual checklist provided confidence that the findings were an adequate representation of patient experience of distal tibia or ankle fracture. A central concept of ‘being the same but different’ conveyed the substantial disruption to patients’ self-identity caused by their injury. Patient experience of ‘being the same but different’ was expressed through three interrelated themes, with seven subthemes: i) being proactive where persistence, doing things differently and keeping busy prevailed; ii) living with change including symptoms, and living differently due to challenges at work and leisure; and iii) striving for normality, adapting while lacking in confidence, and feeling fearful and concerned about the future. Conclusion: Ankle injuries were disruptive, draining, and impacted on patients’ wellbeing. Substantial short- and longer-term challenges were experienced during recovery. Rehabilitation and psychosocial treatment strategies may help to ameliorate these challenges. Patients may benefit from clinicians being cognisant of patient experience when assessing, treating, and discussing expectations and outcomes with patients. Cite this article: Bone Jt Open 2023;4(3):188–197.