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Minimum Important Change for the Patient Evaluation Measure in patients with finger fractures and joint injuries
Get PDFThe Minimum Important Change of the Patient Evaluation Measure for patients recovering from a finger fracture or joint injury was estimated to aid the design of future trials. Data from the Patient Outcomes for Finger Fractures and Joint Injuries prospective cohort study were used. Sixty participants were included. Patients were given the Patient Evaluation Measure questionnaire at baseline and at 6, 12 and 24 weeks with corresponding anchor questions. The Minimum Important Change values for the Patient Evaluation Measure at 24 weeks was between 12 and 17 depending on the statistical estimation method used. Although some variation existed across differing time-points, the range was broadly consistent. The Minimal Detectable Change was estimated as between 9 and 11
Preferences for quality of life versus length of life in older women deciding about treatment for early breast cancer: A cross-sectional sub-analysis of the Bridging the Age Gap study
No full textIntroduction: Prioritising quality of life (QoL) or length of life is often necessary in the decision-making process for cancer care. This may be complicated in patients with limited life expectancy due to age and comorbidities. Older women with early breast cancer often receive non-standard care (primary endocrine therapy [PET] or omission of chemotherapy or radiotherapy) to reduce treatment morbidity and maintain QoL. We aimed to determine the perceived relative influence of QoL versus length of life in treatment decision making by older women with early (potentially curable) breast cancer. Materials and Methods: This was a sub-study of the Age Gap multi-centre, cohort study, which prospectively recruited women >70 yrs. with early breast cancer. Baseline demographics, health characteristics, and QoL scores were analysed alongside a bespoke questionnaire to assess QoL and length of life preferences, including a modified version of the validated quality/quantity questionnaire, in a subset of the main study. Results: The questionnaire was sent to 308 patients and 194 (63 %) were returned by participants with a median age of 75 years (range 70–93). Of these, 14 had PET and 180 had standard treatment (ST) (surgery +/− adjuvant therapy) including 37 who had chemotherapy. The PET group was older (median age 83.5 versus 76 years) and in poorer health (9/14; 64.3 % patients had one or more comorbidities versus 69/144; 47.9 %) with inferior baseline physical domain QoL scores. Patients who received PET valued QoL and length of life equally (Q score 0.87, L score 0.91), and patients who received chemotherapy favoured length of life over QoL (Q score 0.67, L score 0.86). Subgroup analysis showed a small correlation between increasing age and QoL preferences (Spearman's r = 0.2, P < 0.009). There was no correlation between co-morbidities, frailty, or global QoL and length of life/QoL preferences. Discussion: Older women with early breast cancer valued length of life and QoL highly, with an association between preference for QoL and less aggressive treatment choices. Relative QoL preference increased with advancing age. More research is needed to define QoL determinants and outcomes following treatment to help patients make decisions that reflect their priorities. Trial Registration Number: ISRCTN: 46099296
Evolution of Preclinical Models for Glioblastoma Modelling and Drug Screening
Get PDFPurpose of ReviewIsocitrate dehydrogenase wild-type glioblastoma is an extremely aggressive and fatal primary brain tumour, characterised by extensive heterogeneity and diffuse infiltration of brain parenchyma. Despite multimodal treatment and diverse research efforts to develop novel therapies, there has been limited success in improving patient outcomes. Constructing physiologically relevant preclinical models is essential to optimising drug screening processes and identifying more effective treatments.Recent FindingsTraditional in-vitro models have provided critical insights into glioblastoma pathophysiology; however, they are limited in their ability to recapitulate the complex tumour microenvironment and its interactions with surrounding cells. In-vivo models offer a more physiologically relevant context, but often do not fully represent human pathology, are expensive, and time-consuming. These limitations have contributed to the low translational success of therapies from trials to clinic. Organoid and glioblastoma-on-a-chip technology represent significant advances in glioblastoma modelling and enable the replication of key features of the human tumour microenvironment, including its structural, mechanical, and biochemical properties. Organoids provide a 3D system that captures cellular heterogeneity and tumour architecture, while microfluidic chips offer dynamic systems capable of mimicking vascularisation and nutrient exchange. Together, these technologies hold tremendous potential for high throughput drug screening and personalised, precision medicine.SummaryThis review explores the evolution of preclinical models in glioblastoma modelling and drug screening, emphasising the transition from traditional systems to more advanced organoid and microfluidic platforms. Furthermore, it aims to evaluate the advantages and limitations of both traditional and next-generation models, investigating their combined potential to address current challenges by integrating complementary aspects of specific models and techniques
Womb Politics: The Pregnant Body and Archaeologies of Absence
Get PDFPregnancy encompasses core socio-political issues: kinship, demography, religion, gender and more. In any society, the ontology of the pregnant body and the embryo-fetus holds core existential concerns. Is a pregnant body one or two beings? When does personhood begin? Yet, pregnancy is still a marginal topic in archaeology, and its onto-political consequences have scarcely been raised. It would be ludicrous to claim that pregnancy or childbirth is part of the grand narratives of prehistory. Also in scholarship centring theoretical perspectives on the body and personhood is the pregnant body absent. This article poses fundamental questions of the body-politics of pregnancy. We develop concepts from material feminism, medical ethics and philosophy to interrogate pregnancy, and provide a case study to demonstrate how these concepts can work in practice from the Viking Age. The questions posed, however, are not limited to the Viking period. Our overall objective is to centre pregnancy as a philosophical and political concern in archaeology writ large. We develop new thinking and language to this end, which can be used to examine the politics of pregnancy in other periods and regions. Ultimately, we discuss the absence-making of pregnant bodies from our sources as well as from archaeological discourse
Constraining accretion physics with gravitational waves from eccentric extreme-mass-ratio inspirals
Get PDFWe study the evolution of eccentric, equatorial extreme-mass-ratio inspirals (EMRIs) immersed in the accretion disks of active galactic nuclei. We find that single gravitational-wave observations from these systems could provide measurements with ∼10% relative precision of, simultaneously, the disk viscosity and mass accretion rate of the central supermassive black hole. This is possible when the EMRI transitions, within the observation time, from supersonic to subsonic motion relative to the disk gas, for eccentricities ≳0.025–0.1. The estimate of the accretion rate would assist in the identification of the EMRI’s host galaxy, or the observation of a direct electromagnetic counterpart, improving the chances of using these sources as cosmological sirens. Our work highlights the rich phenomenology of binary evolution in astrophysical environments and the need to improve the modeling and analysis of these systems for future gravitational-wave astronomy
Predicting the replicability of social and behavioural science claims in COVID-19 preprints
Get PDFReplications are important for assessing the reliability of published findings. However, they are costly, and it is infeasible to replicate everything. Accurate, fast, lower-cost alternatives such as eliciting predictions could accelerate assessment for rapid policy implementation in a crisis and help guide a more efficient allocation of scarce replication resources. We elicited judgements from participants on 100 claims from preprints about an emerging area of research (COVID-19 pandemic) using an interactive structured elicitation protocol, and we conducted 29 new high-powered replications. After interacting with their peers, participant groups with lower task expertise (‘beginners’) updated their estimates and confidence in their judgements significantly more than groups with greater task expertise (‘experienced’). For experienced individuals, the average accuracy was 0.57 (95% CI: [0.53, 0.61]) after interaction, and they correctly classified 61% of claims; beginners’ average accuracy was 0.58 (95% CI: [0.54, 0.62]), correctly classifying 69% of claims. The difference in accuracy between groups was not statistically significant and their judgements on the full set of claims were correlated (r(98) = 0.48, P < 0.001). These results suggest that both beginners and more-experienced participants using a structured process have some ability to make better-than-chance predictions about the reliability of ‘fast science’ under conditions of high uncertainty. However, given the importance of such assessments for making evidence-based critical decisions in a crisis, more research is required to understand who the right experts in forecasting replicability are and how their judgements ought to be elicited
Molecular xenomonitoring of Schistosoma mansoni infections in Biomphalaria choanomphala at Lake Victoria, East Africa: Assessing roles of abiotic and biotic factors
Get PDFLake Victoria is a well-known hot spot for intestinal schistosomiasis, caused by infection with the trematode Schistosoma mansoni. The snail intermediate hosts of this parasite are Biomphalaria snails, with Biomphalaria choanomphala being the predominant intermediate host within Lake Victoria. The prevalence of S. mansoni infection within snail populations is influenced by both biotic and abiotic factors, including the physical and chemical characteristics of their environment, the incidence of infection in human populations (and reservoir hosts) and the level of genetic compatibility between the parasite and the host. Using molecular xenomonitoring, we measured the prevalence of S. mansoni infection within B. choanomphala populations along the Kenyan, Tanzanian and Ugandan shorelines of Lake Victoria and related this to the abiotic (habitat type, water depth, turbulence, temperature, conductivity, total dissolved solids, salinity, pH level) and biotic (B. choanomphala abundance, genetic diversity of host snail populations) factors of the lake. The overall mean prevalence of S. mansoni infection at Lake Victoria was 9.3%, with the highest prevalence of infection occurring on the Tanzanian shoreline (13.1%), followed by the Ugandan (8.2%) and Kenyan (4.7%) shorelines. There was a significant difference in B. choanomphala abundance, water temperature, conductivity, salinity, total dissolved solids and major anion/cation concentrations between the Kenyan, Tanzanian and Ugandan shorelines of Lake Victoria. A Spearman's rank analysis found that the prevalence of S. mansoni infection had a significant, positive relationship with higher levels of B. choanomphala abundance, water acidity, and cation (Ca2+, Mg2+) concentrations. Additionally, we observed that sites with S. mansoni infection correlated with B. choanomphala populations with a higher mean haplotype diversity score compared to sites found without infection, though there was no significant relationship between the prevalence of infection and B. choanomphala haplotype diversity scores. Although our analysis is based upon an archival and unique collection of Biomphalaria snails, the abiotic and biotic relationships uncovered are useful for eco-epidemiological comparisons of intestinal schistosomiasis across Lake Victoria in future
Non-inferiority trials in stroke research: what are they, and how should we interpret them?
Get PDFRandomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research
The Impact of Motivation on Sustained Attention in Very Preterm and Term-born Children: An ERP Study
Get PDFObjective:To compare the effect of motivational features on sustained attention in children born very preterm and at term.Method:EEG was recorded while 34 8-to-11-year-old children born very preterm and 34 term-born peers completed two variants of a cued continuous performance task (CPT-AX); a standard CPT-AX with basic shape stimuli, and structurally similar motivating variant, with a storyline, familiar characters, and feedback.Results:Higher hit rates, quicker response times and larger event-related potential (ERP) amplitudes were observed during the motivating, compared with the standard, task. Although groups did not differ in task performance, between-task differences in ERPs associated with orienting were larger in term-born than very preterm children.Conclusion:The findings add to previous evidence of disruption to the brain networks that support salience detection and selective attention in children born preterm. Manipulations that increase intrinsic motivation can promote sustained attention in both term-born and very preterm children
Pro-competitive horizontal merger with cost reducing investments and network externalities
Get PDFWe show that a merger can be pro-competitive in an industry with horizontally differentiated network goods and cost reducing investments. If there is firm-specific (industry-wide) network compatibility, the merged firm may produce all the products or one product (the merged firm produces all the products). Under both firm-specific and industry-wide compatibilities, merger may increase consumer surplus even for weak network externalities if the products are not close substitutes. In the case of firm-specific (industry-wide) network compatibility, there are situations where merger reduces (increases) consumer surplus under network externalities but increases (reduces) consumer surplus under no network externality. Hence, the antitrust authorities may (may not) need to be overly concerned about mergers in the presence of network externalities if there is firm-specific (industry-wide) network compatibility
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