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Patient-centered approach to benefit–risk characterization using number needed to benefit and number needed to harm: Advanced non–small-cell lung cancer
No full textThis work summarizes the benefit and risk of the results of clinical trials submitted to the US Food and Drug Administration of therapies for the treatment of non–small cell lung cancer (NSCLC) using number needed to benefit (NNB) and number needed to harm (NNH) metrics. NNB and NNH metrics have been reported as potentially being more patient centric and more intuitive to medical practitioners than more common metrics, such as the hazard ratio, and valuable to medical practitioners in complementing other metrics, such as the median time to event. This approach involved the characterization of efficacy and safety results in terms of NNB and NNH of 30 clinical trials in advanced NSCLC supporting US Food and Drug Administration approval decisions from 2003 to 2017. We assessed trends of NNB over time of treatment (eg, for programmed death 1 inhibitors) and variation of NNB across subpopulations (eg, characterized by epidermal growth factor receptor mutation, programmed death ligand 1 expression, Eastern Cooperative Oncology Group performance status, age, and extent of disease progression). Furthermore, the evolution of NNB of treatments for advanced NSCLC was charted from 2003 to 2017. Across subpopulations, NNB, on average, was 4 patients for approved targeted therapies in molecularly enriched populations, 11 patients for approved therapies in nonmolecularly enriched populations, and 23 patients for withdrawn or unapproved therapies. Furthermore, the NNB analysis showed variation for attributes of epidermal growth factor receptor mutations, level of programmed death 1 expression, Eastern Cooperative Oncology Group performance status, etc. When considering the best-case subpopulations and available drugs, the NNB frontier reduced from an estimated value of 7.7 in 2003 to an estimated value of 2.5 in 2017 at the estimated median overall survival—equal to 6 months—of an untreated patient.US Food and Drug Administratio
Review and evaluation of clean hydrogen production by the copper–chlorine thermochemical cycle
No full textThis paper focuses on the various development areas of the copper-chlorine (Cu–Cl) cycle for hydrogen production which have been actively advanced over the past decade. Recent developments by the international research groups are reported for the individual processes and reactor designs within the Cu–Cl cycle. Accurate prediction of thermo-physical and thermo-chemical properties is critical for the reliable modeling and design of the Cu–Cl cycle. The latest engineering scale-up developments, particularly for the electrolysis and hydrolysis reactors, are presented. New findings on the numerical analysis and experimental measurements are also presented. Recommendations are reported on heat exchanger designs compatible with the chemical compounds for heat recovery and system integration. Furthermore, the scaled-up laboratory equipment for each step of Cu–Cl cycle, and an integrated facility (with a capacity of 100 g H2/day) at the University of Ontario Institute of Technology (UOIT) are presented
What came out of visual memory: Inferences from decay of difference-thresholds
No full textMeans and standard deviations of psychophysical measurements are first and second statistical moments that reflect neuralmechanisms underlying the measured sensation: for example, standard deviations of hue matches are difference-thresholds thatreflect the color pathways’spectral response. Might memory psychophysics yield similar insight into neural mechanismsunderlying recognition? Five experiments measured memory means and difference-thresholds: Means of monochromatic huematches made from memory hardly changed with memory time. Hue memory remained consistent even though the variability ofthose matches increased exponentially as memory time increased to 14 s. This indicates the loss of accuracy in the memoryresulted from a random decay of the stored information. Nevertheless, the hue memory difference-thresholds as a function ofwavelength continued to resemble sensory difference-threshold functions as memory time increased. Similar results obtained bydichoptic matches indicated this resemblance was not a retinal effect. Line and grating orientation memory difference-thresholdsalso retained their similarity to sensory difference-threshold functions as memory time increased. The similarity was not someartifact of measuring difference-thresholds by matching because such results were also obtained using a forced-choice method.Similarity of memory discrimination functions to sensory functions is quantitative evidence that, despite decay, activity retrievedfrom memory resembles the sensory responses used when two stimuli are compared simultaneously. Feasibility of this conclu-sion was tested by modeling the memory-matching procedure. It produced difference-thresholds resembling those obtained withsimultaneous matches when the stored signal had decayed to 10%. Together these results provide“inside”evidence that corticalactivity resembling sensory responses underlie recognition.Natural Sciences and Engineering Research Council of CanadaMaritime Provinces Higher Education Commissio
Determination of dairy cattle euthanasia criteria and analysis of barriers to humane euthanasia in the United States: Dairy producer surveys and focus groups
No full textThere are currently no clear guidelines in the US and some other countries regarding euthanasia decision making timelines for dairy cattle that become injured or ill to the extent that recovery is unlikely or impossible. Our study aimed to identify decision making criteria and the most common factors considered when making and carrying out euthanasia decisions. Dairy producers were recruited to participate in a mailed survey (Part I, 307 completed surveys were returned) or in one of three focus groups (Part II, 8-10 producers/group, n = 24). Part I (survey): Farm owners were most commonly responsible for on-farm euthanasia and most respondents would treat and monitor compromised cattle for a majority of 15 health conditions. Responses were highly variable; for example, 6.3% and 11.7% of respondents would never euthanize a non-ambulatory cow or calf, respectively. Part II (focus groups): Three main themes (animal, human, and farm operation) were identified from discussion which focused primarily on animal welfare (16% of the discussion) and human psychology (16%). Participants expressed a desire to eliminate animal suffering by euthanizing, alongside a wide range of emotional states. Development of specific standards for euthanasia is a critical next step and more research is needed to understand the human emotions surrounding euthanasia decision making.United States Department of Agricultur
Nanocomposites Based on Dendrimers and Layered Molybdenum Disulfide
No full textNanocomposites consisting of molybdenum disulfide (MoS2) and an organometallic dendrimer were synthesized by taking advantage of the exfoliating/restacking properties of lithiated molybdenum disulfide (LiMoS2). Based on the molecular weight of the dendrimer, nine different mole ratios of MoS2 to dendrimer were utilized in order to investigate the upper and lower limit of the dendrimer loading into the restacked MoS2. The developed nanocomposites were characterized by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and variable-temperature electrical conductivity measurements. Our studies revealed that the ideal condition for preparing reproducible monophasic systems is at low dendrimer concentration, no greater than 1:0.125 mole ratio of MoS2 to dendrimer, and no lower than 1:0.002 mole ratio of MoS2 to dendrimer. Biphasic systems can be produced at mole ratio of MoS2 to dendrimer higher than 1:0.125. Additionally, the average crystallite size decreased as the mole ratio of the MoS2 to dendrimer was increased. Specifically, a change from 1:0.002 to 1:0.5 resulted in a noticeable decrease from 365 to 155 Å. The electrical conductivity of the nanocomposites drops as the amount of dendrimer increases. Variable-temperature conductivity data are consistent with a variable-range hopping model
Bayesian risk assessment model of human cryptosporidiosis cases following consumption of raw Eastern oysters (Crassostrea virginica) contaminated with Cryptosporidium oocysts in the Hillsborough River system in Prince Edward Island, Canada
No full textCryptosporidium spp. has been associated with foodborne infectious disease outbreaks; however, it is unclear to what extent raw oyster consumption poses a risk to public health. Control of Cryptosporidium in shellfish harvest seawater in Canada is not mandatory and, despite relay/depuration processes, the parasite can remain viable in oysters for at least a month (depending on initial loads and seawater characteristics). Risks of human infection and illness from exposure to oysters contaminated with Cryptosporidium oocysts were assessed in a Bayesian framework. Two data sets were used: counts of oocysts in oysters harvested in Approved, Restricted, and Prohibited zones of the Hillsborough River system; and oocyst elimination rate from oysters exposed to oocysts in laboratory experiments. A total of 20 scenarios were assessed according to number of oysters consumed in a single serving (1, 10 and 30) and different relay times. The median probability of infection and developing cryptosporidiosis (e.g. illness) due to the consumption of raw oysters in Prince Edward Island was zero for all scenarios. However, the 95th percentiles ranged from 2% to 81% and from 1% to 59% for probability of infection and illness, respectively. When relay times were extended from 14 to 30 days and 10 oysters were consumed in one serving from the Restricted zones, these probabilities were reduced from 35% to 16% and from 15% to 7%, respectively. The 14-day relay period established by Canadian authorities for harvesting in Restricted zones seems prudent, though insufficient, as this relay period has been shown to be enough to eliminate fecal coliforms but not Cryptosporidium oocysts, which can remain viable in the oyster for over a month. Extending relay periods of 14 and 21 days for oysters harvested in Restricted zones to 30 days is likely insufficient to substantially decrease the probability of infection and illness. The highest risk was found for oysters that originated in Prohibited zones. Our findings suggest that Cryptosporidium oocysts are a potential cause of foodborne infection and illness when consuming raw oysters from Hillsborough River, one of the most important oyster production bays on Prince Edward Island. We discuss data gaps and limitations of this work in order to identify future research that can be used to reduce the uncertainties in predicted risks.Public Health Agency of CanadaFisheries and Oceans Canad
Parameter sensitivity and qualitative analysis of dynamics of ovarian tumor growth model with treatment strategy
No full textIn this paper, we are interested to find the most sensitive parameter, local and global stability of ovarian tumor growth model. For sensitivity analysis, we use Latin Hypercube Sampling (LHS) method to generate sample points and Partial Rank Correlation Coefficient (PRCC) method, uses those sample points to find out which parameters are important for the model. Based on our findings, we suggest some treatment strategies. We investigate the sensitivity of the parameters for tumor volume, y, cell nutrient density, Q and maximum tumor size, ymax. We also use Scatter Plot method using LHS samples to show the consistency of the results obtained by using PRCC. Moreover, we discuss the qualitative analysis of ovarian tumor growth model investigating the local and global stability
Evolving perspectives on urban wildlife and their implications for policy-making in Charlottetown, Prince Edward Island
No full textThis research explores how apparent challenges to good urban wildlife conservation and management in Charlottetown, Prince Edward Island, Canada are shaped by the phenomenon of islandness. The work focuses on a Foucauldian case study of Charlottetown in the context of Prince Edward Island. It includes a narrow theoretical comparison between Charlottetown and Denver, Colorado, to bring islandness into
clearer view. The case study describes some distinct ways of human thought about and behavior towards wild nonhumans that influence wildlife governance in Charlottetown: using, getting rid of, helping, learning about, and being humane towards wild nonhumans. The Denver parallel brings to the fore the question of whether any level of government on Prince Edward Island holds wildlife in the public trust. Overall, the
research suggests that the resolution of human-human conflicts about wild nonhumans and human-wildlife conflicts in Charlottetown should involve informal public trust managers on Prince Edward Island
Influences of the culture of science on nursing knowledge development: Using conceptual frameworks as nursing philosophy in critical care nursing
No full textNursing knowledge development and application are influenced by numerous factors within the context of science and practice. The prevailing culture of science along with an evolving context of increasingly technological environments and rationalization within health care impacts both the generation of nursing knowledge and the practice of nursing. The effects of the culture of science and the context of nursing practice may negatively impact the structure and application of nursing knowledge, how nurses practice, and how nurses understand the patients and families for whom they care. Specifically, the nature of critical care and its highly technical environment make critical care nursing especially vulnerable to these potentially negative influences. The influences of the culture of science and the increasingly technical practice context may result in an overreliance on the natural sciences to guide critical care nursing actions and an associated marginalization of the caring relationship in critical care nursing practice. Within this environment, nursing philosophy may not be foundational to nursing actions; rather, the dominant culture of science and the rationalization of health care may be informing nursing practice. As such, the ideology and goals of nursing may not be central to the practice of critical care nursing. The purpose of this paper is to explore the influence of the culture of science on the development of nursing knowledge and theory. Further, we aim to describe the value of using conceptual frameworks, such as Roy's Adaptation Model, as a nursing philosophy to influence the development of person‐centred nursing knowledge and theory to inform critical care nursing practice as it related to the care of patients and families. In doing so, nursing philosophy is situated as foundational for nursing actions