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batss.surv: A fast and flexible framework in R to simulate Bayesian multi-arm multi-stage clinical trials with time-to-event outcomes
No full textAdaptive clinical trials with time-to-event endpoints are increasingly common. However, implementing such designs in the Bayesian framework has been challenging due to the lack of readily available software and the high computational burden associated with Markov Chain Monte Carlo (MCMC) methods often used for estimating the posterior distributions. Here we present a major extension for time-to-event endpoints to the Bayesian Adaptive Trial Simulator Software (BATSS) R package, enabling flexible and efficient simulation of Bayesian adaptive multi-arm multi-stage (MAMS) designs through a modular and scalable framework. We demonstrate that this extension to BATSS is a powerful tool for evaluating the operating characteristics of trials with time-to-event outcomes with flexible interim analysis schedules that incorporate common adaptive features
Validation of an ELISA assay for measurement of the metabolite of serotonin, 5-Hydroxyindole acetic acid (5-HIAA), in canine urine
No full textObjectives
Serotonin (5-hydroxytryptophan), implicated in a number of canine diseases, has a very short half life in the serum. Urine concentration of its breakdown product 5-hydroxyindole acetic acid after an 8 hour fast is a more reliable measure of circulating serotonin in humans. This study aimed to validate a commercially available ELISA assay to measure 5-hydroxyindole acetic acid concentrations in canine urine by comparing the analytical performance with the gold standard liquid chromatography tandem mass spectrometry
Methods
Urine was collected from 26 dogs undergoing routine diagnostic investigations at one referral centre and rapidly processed and stored prior to testing for 5-hydroxyindole acetic acid using the two methods. Deming regression and Bland-Altman analyses were used to compare the results between the two methods
Results
The ELISA demonstrated acceptable precision and repeatability (coefficient of variation <20%). There was good agreement between the two methods (bias 0.92 µmol/L; 95% limits of agreement -6.44 to 8.29 µmol/L), although the ELISA was not tested at values close to the upper end of the claimed analytical measurement range limit. The ELISA was likely to be very reliable at low concentrations but may exceed acceptable error limits at high concentrations.
Clinical significance
A commercially available ELISA was validated to measure urine 5-hydroxyindole acetic acid. This less invasive method than blood sampling for serotonin should give a more reliable indication of long term serum serotonin concentrations. More studies of normal and diseased dogs are needed to confirm these findings before applying them in a clinical setting
Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community.
No full textGenome sequencing has provided snapshots of the transmission of methicillin-resistant Staphylococcus aureus (MRSA) during suspected outbreaks in isolated hospital wards. Scale-up to populations is now required to establish the full potential of this technology for surveillance. We prospectively identified all individuals over a 12-month period who had at least one MRSA-positive sample processed by a routine diagnostic microbiology laboratory in the East of England, which received samples from three hospitals and 75 general practitioner (GP) practices. We sequenced at least 1 MRSA isolate from 1465 individuals (2282 MRSA isolates) and recorded epidemiological data. An integrated epidemiological and phylogenetic analysis revealed 173 transmission clusters containing between 2 and 44 cases and involving 598 people (40.8%). Of these, 118 clusters (371 people) involved hospital contacts alone, 27 clusters (72 people) involved community contacts alone, and 28 clusters (157 people) had both types of contact. Community- and hospital-associated MRSA lineages were equally capable of transmission in the community, with instances of spread in households, long-term care facilities, and GP practices. Our study provides a comprehensive picture of MRSA transmission in a sampled population of 1465 people and suggests the need to review existing infection control policy and practice
Foreign investment screening mechanisms and emergent geographies of (post)globalization
No full textTechnologically advanced states and large emerging economies increasingly use foreign investment screening mechanisms (FISM) to block inward foreign investment targeting sectors considered critical. Is the proliferation of FISM auguring an era of deglobalization, a re-assertion of national-state sovereignty over globalized economic ties, and the end of neoliberal orthodoxies of liberalized investment regimes? To answer these questions, the article draws upon geographic political economy and legal geographies. It argues that the multiplication of FISM is a response to a strategic context defined by three macrogeographic trends: (1) contemporary industrial restructuring and the salience of intellectual property-based monopolies; (2) a historic episode of centralization of capital driven by strategic mergers and acquisitions; and (3) evolving landscapes of state capitalism under conditions of intensified geoeconomic competition. Although FISM reproduce the fiction of state power as expressing the will of the sovereign nation to defend itself against foreign interference, market distortion, and technology theft, they consist of legally enshrining state authority to support national champions, and making sure they engage favorably with competitive dynamics of capital centralization, notably by conserving their monopoly over key intangible assets and strategic resources. FISM are best seen as tools that explicitly mobilize state power and coercion to aggressively (re)negotiate globalization
Biomimetic Metamaterial-based Interface for Decoding Heterogeneous Mechanodermal Activity
No full textHuman skin acts as a dynamic biomechanical interface that conveys critical physiological and behavioural information through spatiotemporally distributed deformations. Due to the limited capabilities of current sensing technologies, the spatiotemporal diversity of its mechanical cues has remained underutilised to date, preventing these mechanisms from being used to capture and decode the full spectrum of underlying physiological states. In this work, we define this heterogeneous set of mechanical signals as mechanodermal activity (MDA) and introduce the biomimetic metamaterial-based interface (BMMI), an engineered auxetic metamaterial substrate that reproduces the microrelief and mechanoreceptor architecture of natural skin. The BMMI allows selective capture of diverse MDA signals from adjacent skin regions with simultaneous signal amplification and noise suppression, and permits straightforward modulation to accommodate various scenarios. Combined with bespoke algorithms, the wireless BMMI device decodes MDA accurately and robustly for multimodal communication interfaces, unleashing applications in healthcare monitoring and human-machine interaction
Failing to forget: inhibitory-control deficits compromise memory suppression in posttraumatic stress disorder.
No full textMost people have experienced distressing events that they would rather forget. Although memories of such events become less intrusive with time for the majority of people, those with posttraumatic stress disorder (PTSD) are afflicted by vivid, recurrent memories of their trauma. Often triggered by reminders in the daily environment, these memories can cause severe distress and impairment. We propose that difficulties with intrusive memories in PTSD arise in part from a deficit in engaging inhibitory control to suppress episodic retrieval. We tested this hypothesis by adapting the think/no-think paradigm to investigate voluntary memory suppression of aversive scenes cued by naturalistic reminders. Retrieval suppression was compromised significantly in PTSD patients, compared with trauma-exposed control participants. Furthermore, patients with the largest deficits in suppression-induced forgetting were also those with the most severe PTSD symptoms. These results raise the possibility that prefrontal mechanisms supporting inhibitory control over memory are impaired in PTSD
A stacked ensemble learning framework with logistic regression meta-learner for thermal comfort prediction
No full textThermal comfort is a critical determinant of human health, well-being and productivity, and is also integral to promoting energy efficiency. The predicted mean vote is the most recognized method for estimating the average thermal experience amongst a group of individuals within built environments. However, the method's reliance on climatic parameters that are difficult and resource-intensive to measure, as well as physiological parameters that require self-reporting, introduces significant practical limitations for real-world applications. The present work aims to address these limitations by proposing a lightweight predictive framework for effective, streamlined thermal comfort classification that relies on a reduced input feature space comprising the easy-to-measure and low-cost climatic parameters of air temperature and relative humidity, and the seasonal standardized approximation for the physiological parameter of clothing insulation. Leveraging an ensemble learning architecture with random forest, k-nearest neighbours, CatBoost and multi-layer perceptron as weak learners and logistic regression as a meta-learner, the proposed framework demonstrated an overall predictive accuracy of 85.8% in estimating the average thermal experience. It adequately handled the class imbalance across thermal discomfort states, particularly those underrepresented, further underscoring its robust performance. The proposed framework could emerge as a scalable and efficient approach for estimating thermal comfort in real-world applications
Manet and Neoliberalism: The Case of Salman Toor
No full textDeep into its latest comeback, more obsessed than ever by its own history, contemporary painting keeps rediscovering that history in the reworked contents of modernism’s first masterworks. Compositions recur; identities change. In Salman Toor’s The Bar on East 13th (2019), the Folies-Bergère becomes a Manhattan gay bar, Édouard Manet’s barmaid an androgynous barman. Such switching of content has become so prominent a feature of contemporary painting as almost to amount to a new genre. Figurative painters are celebrated as, simultaneously, champions of identity and conservers of tradition. I argue, by contrast, that the new paradigm is fundamentally antitraditional. If Toor and his peers can’t stop coming back to Manet, this is to reaffirm, each time, the inaccessibility of pictorial values such as difficulty, reserve, and autonomy, for which his painting once stood. This is no bad thing; rather, it bespeaks a kind of painting attuned to those forces in contemporary culture—digitization, globalization, and neoliberalism—that have rendered those values illegible
Correction: Conductometric sensor for potassium ion profiling using lipophilic salt-incorporated non-toxic ion-selective membrane
No full textBayesian model averaging for partial ordering continual reassessment methods.
No full textPhase I clinical trials are essential to bringing novel therapies from chemical development to widespread use. Traditional approaches to dose-finding in Phase I trials, such as the '3 + 3' method and the continual reassessment method (CRM), provide a principled approach for escalating across dose levels. However, these methods lack the ability to incorporate uncertainty regarding the dose-toxicity ordering as found in combination drug trials. Under this setting, dose levels vary across multiple drugs simultaneously, leading to multiple possible dose-toxicity orderings. The CRM for partial ordering (POCRM) extends to these settings by allowing for multiple dose-toxicity orderings. In this work, it is shown that the POCRM is vulnerable to 'estimation incoherency' whereby toxicity estimates shift in an illogical way, threatening patient safety and undermining clinician trust in dose-finding models. To this end, the Bayesian model averaged POCRM (BMA-POCRM) is formalized. BMA-POCRM uses Bayesian model averaging to take into account all possible orderings simultaneously, reducing the frequency of estimation incoherencies. We derive novel theoretical guarantees on the estimation coherency of the POCRM and BMA-POCRM. The effectiveness of BMA-POCRM in drug combination settings is demonstrated through a specific instance of estimate incoherency of POCRM and simulation studies. The results highlight the improved safety, accuracy, and reduced occurrence of estimate incoherency in trials applying the BMA-POCRM relative to the POCRM model