Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context

College Students’ Images of Mathematicians and Mathematical Careers

In this paper we report our findings of college students’ images of mathematicians and we reflect on different methodologies used to assess this information. The study reported in this paper was conducted in two stages. During the first stage, we asked 179 college students to “draw a mathematician” and also asked them to list five characteristics and five careers for a mathematician. In the second stage of the study, we conducted four focus group interviews with a total of twelve college students. During the focus group interviews, we showed the students 16 photos of real people and asked them to determine which they think are mathematicians and which are not. We found that college students do hold certain stereotypic images of mathematicians and that different perspectives arose based on the different research methodologies. In this paper, we argue for the need to go beyond relying solely on the “draw a mathematician” test and we conclude with a discussion on the implications that stereotypic images of mathematicians have on the mathematical workforce

The development and theoretical application of an implementation framework for dialectical behaviour therapy:a critical literature review

Background: Dialectical behaviour therapy (DBT) is a third wave behaviour therapy combining behaviour based components with elements of mindfulness. Although DBT effectiveness has been explored, relatively little attention has been given to its implementation. Frameworks are often the basis for gathering information about implementation and can also direct how the implementation of an intervention is conducted. Using existing implementation frameworks, this critical literature review scoped the DBT implementation literature to develop and refine a bespoke DBT implementation framework. Method and results: The initial framework was developed by consolidating existing implementation frameworks and published guidance on DBT implementation. The critical literature review retrieved papers from Medline, CINAHL, PsycInfo, PubMed, and the reference lists of included papers. Framework elements were used as codes which were applied to the literature and guided the synthesis. Findings from the synthesis refined the framework.The critical literature review retrieved 60 papers but only 14 of these explicitly focused on implementation. The DBT implementation framework captured all the execution barriers and facilitators described in the literature. However, the evidence synthesis led to a more parsimonious framework as some elements (e.g., research and published guidance) were seldom discussed in DBT implementation. Conclusion: To our knowledge this is the first published review exploring DBT implementation. The literature synthesis suggests some tentative recommendations which warrant further exploration. For instance, if DBT implementation is not pre-planned, having someone in the organisation who champions DBT can be advantageous. However, as the literature is limited and has methodological limitations, further prospective studies of DBT implementation are needed

Targeted Multispectral Filter Array Design for Endoscopic Cancer Detection in the Gastrointestinal Tract

Colour differences between healthy and diseased tissue in the gastrointestinal tract are detected visually by clinicians during white light endoscopy (WLE); however, the earliest signs of disease are often just a slightly different shade of pink compared to healthy tissue. Here, we propose to target alternative colours for imaging to improve contrast using custom multispectral filter arrays (MSFAs) that could be deployed in an endoscopic chip-on-tip configuration. Using an open-source toolbox, Opti-MSFA, we examined the optimal design of MSFAs for early cancer detection in the gastrointestinal tract. The toolbox was first extended to use additional classification models (k-Nearest Neighbour, Support Vector Machine, and Spectral Angle Mapper). Using input spectral data from published clinical trials examining the oesophagus and colon, we optimised the design of MSFAs with 3 to 9 different bands. We examined the variation of the spectral and spatial classification accuracy as a function of number of bands. The MSFA designs have high classification accuracies, suggesting that future implementation in endoscopy hardware could potentially enable improved early detection of disease in the gastrointestinal tract during routine screening and surveillance. Optimal MSFA configurations can achieve similar classification accuracies as the full spectral data in an implementation that could be realised in far simpler hardware. The reduced number of spectral bands could enable future deployment of multispectral imaging in an endoscopic chip-on-tip configuration.Comment: 29 page

Characterising the seasonal and geographical variability in tropospheric ozone, stratospheric influence and recent changes

The stratospheric contribution to tropospheric ozone (O3) has been a subject of much debate in recent decades but is known to have an important influence. Recent improvements in diagnostic and modelling tools provide new evidence that the stratosphere has a much larger influence than previously thought. This study aims to characterise the seasonal and geographical distribution of tropospheric ozone, its variability, and its changes and provide quantification of the stratospheric influence on these measures. To this end, we evaluate hindcast specified-dynamics chemistry–climate model (CCM) simulations from the European Centre for Medium-Range Weather Forecasts – Hamburg (ECHAM)/Modular Earth Submodel System (MESSy) Atmospheric Chemistry (EMAC) model and the Canadian Middle Atmosphere Model (CMAM), as contributed to the International Global Atmospheric Chemistry – Stratosphere-troposphere Processes And their Role in Climate (IGAC-SPARC) (IGAC–SPARC) Chemistry Climate Model Initiative (CCMI) activity, together with satellite observations from the Ozone Monitoring Instrument (OMI) and ozone-sonde profile measurements from the World Ozone and Ultraviolet Radiation Data Centre (WOUDC) over a period of concurrent data availability (2005–2010). An overall positive, seasonally dependent bias in 1000–450 hPa (∼0–5.5 km) sub-column ozone is found for EMAC, ranging from 2 to 8 Dobson units (DU), whereas CMAM is found to be in closer agreement with the observations, although with substantial seasonal and regional variation in the sign and magnitude of the bias (∼±4 DU). Although the application of OMI averaging kernels (AKs) improves agreement with model estimates from both EMAC and CMAM as expected, comparisons with ozone-sondes indicate a positive ozone bias in the lower stratosphere in CMAM, together with a negative bias in the troposphere resulting from a likely underestimation of photochemical ozone production. This has ramifications for diagnosing the level of model–measurement agreement. Model variability is found to be more similar in magnitude to that implied from ozone-sondes in comparison with OMI, which has significantly larger variability. Noting the overall consistency of the CCMs, the influence of the model chemistry schemes and internal dynamics is discussed in relation to the inter-model differences found. In particular, it is inferred that CMAM simulates a faster and shallower Brewer–Dobson circulation (BDC) compared to both EMAC and observational estimates, which has implications for the distribution and magnitude of the downward flux of stratospheric ozone over the most recent climatological period (1980–2010). Nonetheless, it is shown that the stratospheric influence on tropospheric ozone is significant and is estimated to exceed 50 % in the wintertime extratropics, even in the lower troposphere. Finally, long-term changes in the CCM ozone tracers are calculated for different seasons. An overall statistically significant increase in tropospheric ozone is found across much of the world but particularly in the Northern Hemisphere and in the middle to upper troposphere, where the increase is on the order of 4–6 ppbv (5 %–10 %) between 1980–1989 and 2001–2010. Our model study implies that attribution from stratosphere–troposphere exchange (STE) to such ozone changes ranges from 25 % to 30 % at the surface to as much as 50 %–80 % in the upper troposphere–lower stratosphere (UTLS) across some regions of the world, including western Eurasia, eastern North America, the South Pacific and the southern Indian Ocean. These findings highlight the importance of a well-resolved stratosphere in simulations of tropospheric ozone and its implications for the radiative forcing, air quality and oxidation capacity of the troposphere

Animal models in cartilage research

Coral reefs are in decline worldwide. While coral reef managers are limited in their ability to tackle global challenges, such as ocean warming, managing local threats can increase the resilience of coral reefs to these global threats. One such local threat is high sediment inputs to coastal waters due to terrestrial over-grazing. Increases in terrestrial sediment input into coral reefs are associated with increased coral mortality, reduced growth rates, and changes in species composition, as well as alterations to fish communities. We used general linear models to investigate the link between vegetation ground cover and tree biomass index, within a dry-forest ecosystem, to coral cover, fish communities and visibility in the case study site of Bonaire, Caribbean Netherlands. We found a positive relationship between ground cover and coral cover below 10 m depth, and a negative relationship between tree biomass index and coral cover below 10 m. Greater ground cover is associated to sediment anchored through root systems, and higher surface complexity, slowing water flow, which would otherwise transport sediment. The negative relationship between tree biomass index and coral cover is unexpected, and may be a result of the deep roots associated with dry-forest trees, due to limited availability of water, which therefore do not anchor surface sediment, or contribute to surface complexity. Our analysis provides evidence that coral reef managers could improve reef health through engaging in terrestrial ecosystem protection, for example by taking steps to reduce grazing pressures, or in restoring degraded forest ecosystems

Comparing directed functional connectivity between groups with confirmatory subgrouping GIMME

Connectivity modeling in functional neuroimaging has become widely used method of analysis for understanding functional architecture. One method for deriving directed connectivity models is Group Iterative Multiple Model Estimation (GIMME; Gates and Molenaar, 2012). GIMME looks for commonalities across the sample to detect signal from noise and arrive at edges that exist across the majority in the group ("group-level edges") and individual-level edges. In this way, GIMME obtains generalizable results via the group-level edges while also allowing for between subject heterogeneity in connectivity, moving the field closer to obtaining reliable personalized connectivity maps. In this article, we present a novel extension of GIMME, confirmatory subgrouping GIMME, which estimates subgroup-level edges for a priori known groups (e.g. typically developing controls vs. clinical group). Detecting edges that consistently exist for individuals within predefined subgroups aids in interpretation of the heterogeneity in connectivity maps and allows for subgroup-specific inferences. We describe this algorithm, as well as several methods to examine the results. We present an empirical example that finds similarities and differences in resting state functional connectivity among four groups of children: typically developing controls (TDC), children with autism spectrum disorder (ASD), children with Inattentive (ADHD-I) and Combined (ADHD-C) Type ADHD. Findings from this study suggest common involvement of the left Broca's area in all the clinical groups, as well as several unique patterns of functional connectivity specific to a given disorder. Overall, the current approach and proof of principle findings highlight a novel and reliable tool for capturing heterogeneity in complex mental health disorders

PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation

P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1β, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1–p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells

Spectrally tailored 'hyperpixel' filter arrays for imaging of chemical compositions

We present a method for designing and fabricating 'HyperPixels': pixel filter arrays with custom spectral transmission properties that enable efficient imaging of specific chromophores or fluorophores. Multispectral imaging typically targets particular spectral bands to uncover the spectral properties of tissue in combination with spatial resolution. Unmixing spectral properties can uncover the type and quantity of chromophores or fluorophores due to their unique spectral absorption or emission. Pixelated filter arrays atop imaging sensors are low-cost techniques used to achieve multispectral imaging. Typically, the filter pixels exhibit bandpass spectral behaviour, allowing only a fraction of the incident light to reach the sensor. As a result, narrowband filter pixels trade off high spectral resolution with optical power loss. A way to avoid this issue and improve the signal to noise ratio (SNR) for individual targets is to use a filter array where individual pixels are matched to a target chemical compound's reflectance or emission spectrum. Simulations show a > 5-fold improvement in SNR under realistic noise conditions. These matched optical filters can also reduce the complexity of software or hardware spectral unmixing algorithms, offering the potential for real-time imaging of target compounds. We present a method for tailoring spectral transmission of individual pixels by building HyperPixels comprising multiple Fabry-Perot resonator subpixels with varying bandpass properties (FWHM = approximately 50-60 nm, thicknesses 75-150 nm) that collectively have the desired transmission spectrum. We used a numerical optimization process to design filter arrays for simultaneous detection of methylene blue and indocyanine green, commonly used in cancer diagnostics by clinicians. We then fabricated filters for indocyanine green detection using grayscale lithography with pixel sizes down to 5 µm and individual subpixels down to 0.5 µm and characterized them for their spectral properties