Implementation of quantified self technologies in workplaces relies on the ontological premise of Cartesian dualism with mind dominant over body. Contributing to debates in new materialism, we ...demonstrate that workers are now being asked to measure our own productivity and health and well-being in art-houses and warehouses alike in both the global north and south. Workers experience intensified precarity, austerity, intense competition for jobs and anxieties about the replacement of labour-power with robots and other machines as well as, ourselves replaceable, other humans. Workers have internalised the imperative to perform, a subjectification process as we become observing entrepreneurial subjects and observed, objectified labouring bodies. Thinking through the implications of the use of wearable technologies in workplaces, this article shows that these technologies introduce a heightened Taylorist influence on precarious working bodies within neoliberal workplaces.
Dengue is the most rapidly spreading mosquito-borne viral disease of humans worldwide, including southeast Asia region. This review provides a comprehensive overview of questionnaire-related dengue ...studies conducted in the Philippines and evaluates their reliability and validity in these surveys.
A review protocol constructed by a panel of experienced academic reviewers was used to formulate the methodology, research design, search strategy and selection criteria. An extensive literature search was conducted between March-June 2020 in various major electronic biomedical databases including PubMed, EMBASE, MEDLINE and ScienceDirect. A systematic review and meta-analysis (PRISMA) were selected as the preferred item reporting method.
Out of a total of 34 peer-reviewed dengue-related KAP studies that were identified, 15 published from 2000 to April 2020 met the inclusion criteria. Based on the meta-analysis, a poor mean score was obtained for each of knowledge (68.89), attitude (49.86) and preventive practice (64.69). Most respondents were equipped with a good knowledge of the major clinical signs of dengue. Worryingly, 95% of respondents showed several negative attitudes towards dengue prevention, claiming that this was not possible and that enacting preventive practices was not their responsibility. Interestingly, television or radio was claimed as the main source of gaining dengue information (range 50-95%). Lastly, only five articles (33.3%) piloted or pretested their questionnaire before surveying, of which three reported Cronbach's alpha coefficient (range 0.70 to 0.90).
This review indicates that to combat the growing public health threat of dengue to the Philippines, we need the active participation of resident communities, full engagement of healthcare personnel, promotion of awareness campaigns, and access to safe complementary and alternative medicines. Importantly, the psychometric properties of each questionnaire should be assessed rigorously.
Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that ...are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development.
The ordered assembly of tau protein into filaments characterizes several neurodegenerative diseases, which are called tauopathies. It was previously reported that, by cryo-electron microscopy, the ...structures of tau filaments from Alzheimer's disease
, Pick's disease
, chronic traumatic encephalopathy
and corticobasal degeneration
are distinct. Here we show that the structures of tau filaments from progressive supranuclear palsy (PSP) define a new three-layered fold. Moreover, the structures of tau filaments from globular glial tauopathy are similar to those from PSP. The tau filament fold of argyrophilic grain disease (AGD) differs, instead resembling the four-layered fold of corticobasal degeneration. The AGD fold is also observed in ageing-related tau astrogliopathy. Tau protofilament structures from inherited cases of mutations at positions +3 or +16 in intron 10 of MAPT (the microtubule-associated protein tau gene) are also identical to those from AGD, suggesting that relative overproduction of four-repeat tau can give rise to the AGD fold. Finally, the structures of tau filaments from cases of familial British dementia and familial Danish dementia are the same as those from cases of Alzheimer's disease and primary age-related tauopathy. These findings suggest a hierarchical classification of tauopathies on the basis of their filament folds, which complements clinical diagnosis and neuropathology and also allows the identification of new entities-as we show for a case diagnosed as PSP, but with filament structures that are intermediate between those of globular glial tauopathy and PSP.
Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that ...express programmed death ligand 1 (PD-L1).
In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.
Median progression-free survival was 10.3 months (95% confidence interval CI, 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached range, 1.9+ to 14.5+ months vs. 6.3 months range, 2.1+ to 12.6+), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).
In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .).
In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in ...patients with previously untreated advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab.
Patients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator's choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting.
Three hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively).
With prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy.
The development and use of probabilistic models, particularly Bayesian networks (BN), to support risk‐based decision making is well established. Striking an efficient balance between satisfying model ...complexity and ease of development requires continuous compromise. Codesign, wherein the structural content of the model is developed hand‐in‐hand with the experts who will be accountable for the parameter estimates, shows promise, as do so‐called nonparametric Bayesian networks (NPBNs), which provide a light‐touch approach to capturing complex relationships among nodes. We describe and demonstrate the process of codesigning, building, quantifying, and validating an NPBN model for emerging risks and the consequences of potential management decisions using structured expert judgment (SEJ). We develop a case study of the local spread of a marine pathogen, namely, Bonamia ostreae. The BN was developed through a series of semistructured workshops that incorporated extensive feedback from many experts. The model was then quantified with a combination of field and expert‐elicited data. The IDEA protocol for SEJ was used in its hybrid (remote and face‐to‐face) form to elicit information about more than 100 parameters. This article focuses on the modeling and quantification process, the methodological challenges, and the way these were addressed.
Biological invasions are a growing threat to biodiversity, food security, and economies. Rising pressure from increased global trade requires improving border inspection efficiency. Here, we depart ...from the conventional consignment-by-consignment approach advocated in current inspection standards. Instead, we suggest a broader perspective: evaluating border inspection regimes based on their ability to reduce propagule pressure across entire pathways. Additionally, we demonstrate that most biosecurity pathways exhibit superspreading behavior, that is, consignments from the same pathway have varying infestation rates and contain rare right-tail events (also called overdispersion). We show that greater overdispersion leads to more pronounced diminishing returns, with consequences on the optimal allocation of sampling effort. We leverage these two insights to develop a simple and efficient border inspection regime that can significantly reduce propagule pressure compared to current standards. Our analysis revealed that consignment size is a key driver of biosecurity risk and that sampling proportional to the square root of consignment size is near optimal. In testing, our framework reduced propagule pressure by 31 to 38% compared to current standards. We also identified opportunities to further improve inspection efficiency by considering additional pathway characteristics (i.e., overdispersion parameters, zero inflation, relative risk, sampling cost, detectability) and developed solutions for these more complex scenarios. We anticipate our result will mitigate biological invasion risk with significant implications for biodiversity conservation, food security, and economies worldwide.
While no single model can exactly recapitulate all aspects of multiple sclerosis (MS), animal models are essential in understanding the induction and pathogenesis of the disease and to develop ...therapeutic strategies that limit disease progression and eventually lead to effective treatments for the human disease. Several different models of MS exist, but by far the best understood and most commonly used is the rodent model of experimental autoimmune encephalomyelitis (EAE). This model is typically induced by either active immunization with myelin-derived proteins or peptides in adjuvant or by passive transfer of activated myelin-specific CD4+ T lymphocytes. Mouse models are most frequently used because of the inbred genotype of laboratory mice, their rapid breeding capacity, the ease of genetic manipulation, and availability of transgenic and knockout mice to facilitate mechanistic studies. Although not all therapeutic strategies for MS have been developed in EAE, all of the current US Food and Drug Administration (FDA)-approved immunomodulatory drugs are effective to some degree in treating EAE, a strong indicator that EAE is an extremely useful model to study potential treatments for MS. Several therapies, such as glatiramer acetate (GA: Copaxone), and natalizumab (Tysabri), were tested first in the mouse model of EAE and then went on to clinical trials. Here we discuss the usefulness of the EAE model in understanding basic disease pathophysiology and developing treatments for MS as well as the potential drawbacks of this model.
The first account of the role Britain played in Einstein's life-first by inspiring his teenage passion for physics, then by providing refuge from the Nazis In autumn 1933, Albert Einstein found ...himself living alone in an isolated holiday hut in rural England. There, he toiled peacefully at mathematics while occasionally stepping out for walks or to play his violin. But how had Einstein come to abandon his Berlin home and go "on the run"? In this lively account, Andrew Robinson tells the story of the world's greatest scientist and Britain for the first time, showing why Britain was the perfect refuge for Einstein from rumored assassination by Nazi agents. Young Einstein's passion for British physics, epitomized by Newton, had sparked his scientific development around 1900. British astronomers had confirmed his general theory of relativity, making him internationally famous in 1919. Welcomed by the British people, who helped him campaign against Nazi anti-Semitism, he even intended to become a British citizen. So why did Einstein then leave Britain, never to return to Europe?
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