This groundbreaking edited book, The Routledge Handbook for Advancing Integration in Mixed Methods Research, presents an array of different integration ideas, with contributions from scholars across ...the globe. This handbook represents the first major volume that comprehensively discusses this topic of integration. Perhaps the most fundamental and longstanding question in mixed methods research is: How does one best integrate disparate forms of information to produce the best form of inquiry? Each of the 34 seminal chapters in this handbook accelerates the discussion of integration across a broad range of disciplines, including education, arts-based analyses, and work in the Global South, as well as special topics such as psychometrics and media research. Many of the chapters present new topics that have never been written about before, and all chapters offer cutting-edge approaches to integration. They also offer different perspectives of integration – leading the introductory chapter to offer a new and comprehensive definition for integration, as follows: "referring to the optimal mixing, combining, blending, amalgamating, incorporating, joining, linking, merging, consolidating, or unifying of research approaches, methodologies, philosophies, methods, techniques, concepts, language, modes, disciplines, fields, and/or teams within a single study." The concluding chapter offers a meta-framework that accounts for this definition and is designed to help scholars think more about integration in a way that represents a continuous, dynamic, iterative, interactive, synergistic, and holistic meaning-making process. This handbook will be an essential reference work for all scholars and practitioners using or seeking to use mixed methods in their research.
River regulation and water extraction has significantly altered flow regimes and reduced flood events in many inland river systems. Environmental flows have been adopted in many systems to mitigate ...the ecological impacts of river regulation, however a lack of knowledge regarding the interrelationship between flow regimes, carbon transport and instream productivity make prioritising water management difficult. To address this knowledge gap, we conducted a study on the Namoi River in the Murray-Darling Basin, Australia, monitoring changes in dissolved organic carbon (DOC), nutrient dynamics and planktonic food web structure during a period of variable flows. Nutrient and DOC concentrations were positively correlated with river discharge and zooplankton concentrations were highest post flow events. Planktonic chlorophyll-
a
, increased DOC concentration and higher discharge were the most influential drivers of change in zooplankton communities. Further, our results indicated that flow events increased production through both heterotrophic and autotrophic pathways, significantly boosting zooplankton concentration compared to base flow conditions across all measured flow events. We suggest even small in-channel flow events can be important for increasing basal and zooplankton production in rivers, and therefore should be protected or promoted by environmental flow management, particularly during drought conditions.
The Thresher: Lucky imaging without the waste Hitchcock, J A; Bramich, D M; Foreman-Mackey, D ...
Monthly Notices of the Royal Astronomical Society,
03/2022, Letnik:
511, Številka:
4
Journal Article
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ABSTRACT
In traditional lucky imaging (TLI), many consecutive images of the same scene are taken with a high frame-rate camera, and all but the sharpest images are discarded before constructing the ...final shift-and-add image. Here, we present an alternative image analysis pipeline – The Thresher – for these kinds of data, based on online multi-frame blind deconvolution. It makes use of all available data to obtain the best estimate of the astronomical scene in the context of reasonable computational limits; it does not require prior estimates of the point-spread functions in the images, or knowledge of point sources in the scene that could provide such estimates. Most importantly, the scene it aims to return is the optimum of a justified scalar objective based on the likelihood function. Because it uses the full set of images in the stack, The Thresher outperforms TLI in signal-to-noise ratio; as it accounts for the individual-frame PSFs, it does this without loss of angular resolution. We demonstrate the effectiveness of our algorithm on both simulated data and real Electron-Multiplying CCD images obtained at the Danish 1.54-m telescope (hosted by ESO, La Silla). We also explore the current limitations of the algorithm, and find that for the choice of image model presented here, non-linearities in flux are introduced into the returned scene. Ongoing development of the software can be viewed at https://github.com/jah1994/TheThresher.
Background
Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis.
Methods
We performed ...survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation.
Results
A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio OR 0.30, 95% CI 0.25–0.37 and 0.48 0.31–0.76, respectively). Five‐year OS was lower in patients treated with radiation versus chemoradiation (33.8% 30.3%–37.2% vs. 58.0% 55.8%–60.0%). In patients <70 with no comorbidities this difference persisted (51.0% 44.5%–57.0% versus 66.7% 64.0%–69.3%).
Conclusion
Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis.
•Links between hydrodynamics and ecological responses via a multi-disciplinary study.•Functional representation of bacterial mineralisation improves chlorophyll-a predictions.•Model boundary ...conditions are critical in driving biophysical system response.•Net transport rates and net growth rates affect model's response sensitivity.•Hydrodynamics are important in designing microbial field sampling programs.
Eutrophication due to excess anthropogenic nutrients in waterways is a significant issue worldwide. The pressure-stressor-response of a waterway to excessive nutrient loading is reliant on numerous physical and biological factors, including hydrodynamics and microbial processing. While substantial progress has been made towards simulating these mechanisms there are limited multi-disciplinary studies that relate the physical hydrodynamics of a site with the ecological response from linked laboratory and field studies. This paper presents the development of a coupled hydrodynamic and aquatic ecosystem response model, expanded to include an integrated microbial loop, that allows the explicit representation of heterotrophic bacteria growth and dissolved organic nutrient mineralisation. A unique long-term water quality dataset at an estuary in south-eastern Australia was used to validate and assess the model's sensitivity to complex biophysical processes driving the observed water quality variability. Results indicate that explicit time-varying bacterial mineralisation rates provide a substantially improved understanding of the broader aquatic ecosystem response than assigned fixed bulk rate parameter values, which are typically derived from non-local literature. Implementation of a microbial loop at the study site indicated that the model is sensitive to the boundary conditions, in particular catchment loads, with both net transport rates and the net growth rates of heterotrophic bacteria demonstrating different responses. Under average flow conditions, a smaller net transport and reduced nutrient availability has a pronounced effect of lowering net growth rates through the applied limitation factors. During high flow conditions, freshwater inflows increased net transport and nutrient loads, which resulted in higher net growth rates. Further, temporal variability in water temperature had a compounding effect on the model's response sensitivity. This approach has broader application in other riverine systems subject to eutrophication, and in interrogating linkages in hydrodynamic and microbial mediated processes (e.g., productivity). Future studies are recommended to better understand the sensitivity of aquatic ecosystem response models to microbial net growth rate kinetics at different temperatures and from top-down predation (e.g., zooplankton grazing).
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Abstract
BACKGROUND
The available literature to guide treatment decision making in esthesioneuroblastoma (ENB) is limited.
OBJECTIVE
To define treatment patterns and outcomes in ENB according to ...treatment modality using a large national cancer registry.
METHODS
This study is a retrospective cohort analysis of 931 patients with a diagnosis of ENB who were treated with surgery, radiation therapy, and/or chemotherapy in the United States between the years of 2004 and 2012. Log-rank statistics were used to compare overall survival by primary treatment modality. Logistic regression modeling was used to identify predictors of receipt of postoperative radiotherapy (PORT). Cox proportional hazards modeling was used to determine the survival benefit of PORT. Subgroup analyses identified subgroups that derived the greatest benefit of PORT.
RESULTS
Primary surgery was the most common treatment modality (90%) and resulted in superior survival compared to radiation (P < .01) or chemotherapy (P < .01). On multivariate analysis, PORT was associated with decreased risk of death (hazard ratio HR 0.53, P < .01). PORT showed a survival benefit in Kadish stage C (HR 0.42, P < .01) and D (HR 0.09, P = .01), but not Kadish A (HR 1.17, P = .74) and B (HR 1.37, P = .80). Patients who received chemotherapy derived greater benefit from PORT (HR 0.22, P < .01) compared with those who did not (HR 0.68, P = .13). Predictors of PORT included stage, grade, extent of resection, and chemotherapy use.
CONCLUSION
Best outcomes were obtained in patients undergoing primary surgery. The benefit of PORT was driven by patients with stages C and D disease, and by those also receiving chemotherapy.
Development of therapies with the potential to change the allergic asthmatic disease course will require the discovery of targets that play a central role during the initiation of an allergic ...response, such as those involved in the process of allergen recognition. We use a receptor glycocapture technique to screen for house dust mite (HDM) receptors and identify LMAN1 as a candidate. We verify the ability of LMAN1 to directly bind HDM allergens and demonstrate that LMAN1 is expressed on the surface of dendritic cells (DCs) and airway epithelial cells (AECs) in vivo. Overexpression of LMAN1 downregulates NF-κB signaling in response to inflammatory cytokines or HDM. HDM promotes binding of LMAN1 to the FcRγ and recruitment of SHP1. Last, peripheral DCs of asthmatic individuals show a significant reduction in the expression of LMAN1 compared with healthy controls. These findings have potential implications for the development of therapeutic interventions for atopic disease.
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•Receptor glycocapture screen identifies LMAN1 as an HDM receptor•Binding of LMAN1 to HDM allergens requires LMAN1 CRD•LMAN1 downregulates NF-κB signaling through binding FcRγ and recruitment of SHP1•Asthmatic individuals show reduced cell surface expression of LMAN1 on peripheral DCs
Miller et al. describe the identification of LMAN1 as a receptor for HDM using an unbiased receptor glycocapture screen. Engagement of LMAN1 by HDM restrains inflammatory responses. Such regulatory mechanisms may be disrupted in asthmatic individuals who show reduced expression of LMAN1 on DCs.
To investigate the risk of sensorineural hearing loss (SNHL) in patients with head-and-neck cancer and treated with radiation therapy (RT) or concomitant cisplatin-based chemoradiation, the ...relationship among SNHL and radiation dose to the cochlea, the use of two common cisplatin dose regimens.
A total of 62 head-and-neck cancer patients treated with curative intent were included in this prospective study. Of the patients, 21 received RT alone, 27 received 40 mg/m(2) weekly cisplatin, 13 received 100 mg/m(2) every 3 weeks during RT, and 1 received RT with weekly epidermal growth factor receptor inhibitor antibody. The effect of chemotherapy and RT dose on hearing was determined using a model that accounted for the age and variability between each ear for each patient.
We constructed a model to predict dose-dependent hearing loss for RT or cisplatin-based chemotherapy either alone or in combination. For patients only receiving RT, no significant hearing loss was found at doses to the cochlea of less than 40 Gy. Patients receiving 100 mg/m(2) or 40 mg/m(2) of cisplatin chemotherapy had an estimated +21.5 dB and +9.5 dB hearing loss at 8,000 Hz with low radiation doses (10 Gy), which rose to +38.4 dB and +18.9 dB for high radiation doses (40 Gy).
Use of RT alone with doses of less than 40 Gy did not result in clinically significant hearing loss. High-frequency SNHL was profoundly damaged in patients who received concomitant cisplatin when doses of 100 mg/m(2) were used. The threshold cochlear dose for hearing loss with cisplatin-based chemotherapy and RT was predicted to be 10 Gy. The inner ear radiation dose constraints and cisplatin dose intensity should be considered in the treatment of advanced head-and-neck cancer.
A gene's-eye view of sexual antagonism Hitchcock, Thomas J.; Gardner, Andy
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
08/2020, Letnik:
287, Številka:
1932
Journal Article
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Females and males may face different selection pressures. Accordingly, alleles that confer a benefit for one sex often incur a cost for the other. Classic evolutionary theory holds that the X ...chromosome, whose sex-biased transmission sees it spending more time in females, should value females more than males, whereas autosomes, whose transmission is unbiased, should value both sexes equally. However, recent mathematical and empirical studies indicate that male-beneficial alleles may be more favoured by the X chromosome than by autosomes. Here we develop a gene's-eye-view approach that reconciles the classic view with these recent discordant results, by separating a gene's valuation of female versus male fitness from its ability to induce fitness effects in either sex. We use this framework to generate new comparative predictions for sexually antagonistic evolution in relation to dosage compensation, sex-specific mortality and assortative mating, revealing how molecular mechanisms, ecology and demography drive variation in masculinization versus feminization across the genome.
Despite substantial progress in the development of antiretroviral regimens that durably suppress Human Immunodeficiency Virus (HIV) infection, new agents that maintain high efficacy while further ...optimizing the safety of lifelong, chronic therapy are needed. Tenofovir alafenamide (TAF; formerly known as GS-7340) is a novel prodrug of the antiviral acyclic nucleoside phosphonate tenofovir (TFV) with improved properties relative to tenofovir disoproxil fumarate (TDF). Although potent and generally well tolerated, TDF therapy has been associated with changes in markers of renal function, decreases in bone mineral density and a rare occurrence of serious renal adverse events, including Fanconi's Syndrome. The renal and bone toxicity observed with TDF is associated with high circulating plasma levels of TFV. TAF was discovered to be a more efficient prodrug able to further refine HIV therapy and better address life-long therapy in an older and increasingly comorbid HIV infected population. By enhancing stability in biological matrices while being rapidly activated in cells, TAF produces higher levels of intracellular TFV diphosphate, the pharmacologically active metabolite, in HIV-target cells at substantially reduced oral doses of TFV equivalents. All TFV released in the body is eventually eliminated renally; therefore, lowering the TFV equivalents administered reduces off-target kidney exposure. Effective therapy is thus achieved at approximately 90% lower systemic exposure to TFV, translating to statistically and clinically significant improvement in safety parameters associated with bone mineral density and markers of renal function.
•Once in cells, pharmacologically active tenofovir diphosphate has favorable antiviral activity, selectivity and persistence.•Tenofovir in parent form lacks oral bioavailability and has poor cell membrane permeability.•Tenofovir disoproxil fumarate is generally well tolerated clinically but is associated with effects on the kidney and bone.•Tenofovir alafenamide more efficiently delivers tenofovir to target cells resulting in lower plasma and kidney exposures.•Clinical studies have shown tenofovir alafenamide has reduced impact on markers of renal function and bone mineralization.
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