One of the most common policy prescriptions for overcoming the so-called “resource curse,” particularly for extractive industries, has been to call for greater transparency and accountability from ...governments. However, despite the conceptual attraction of this policy, it has never been empirically proven that resource-rich countries are actually less transparent than other countries, and whether this lack of transparency has had a significant negative effect on economic growth. Using a relatively new index of transparency that has extensive coverage, both across countries and time, the results suggest a strong and robust negative causal association running from (point) resource export revenues to transparency. Furthermore, there is also some evidence that this lack of transparency is associated with a subsequent decrease in economic growth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The range of benefits associated with regular physical activity participation is irrefutable. Despite the well-known benefits, physical inactivity remains one of the major contributing factors to ...ill-health throughout industrialized countries. Traditional lifestyle interventions such as group education or telephone counseling are effective at increasing physical activity participation; however, physical activity levels tend to decline over time. Consumer-based wearable activity trackers that allow users to objectively monitor activity levels are now widely available and may offer an alternative method for assisting individuals to remain physically active.
This review aimed to determine the effects of interventions utilizing consumer-based wearable activity trackers on physical activity participation and sedentary behavior when compared with interventions that do not utilize activity tracker feedback.
A systematic review was performed searching the following databases for studies that included the use of a consumer-based wearable activity tracker to improve physical activity participation: Cochrane Controlled Register of Trials, MEDLINE, PubMed, Scopus, Web of Science, Cumulative Index of Nursing and Allied Health Literature, SPORTDiscus, and Health Technology Assessments. Controlled trials of adults comparing the use of a consumer-based wearable activity tracker with other nonactivity tracker-based interventions were included. The main outcome measures were physical activity participation and sedentary behavior. All studies were assessed for risk of bias, and the Grades of Recommendation, Assessment, Development, and Evaluation system was used to rank the quality of evidence. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement were followed. A random-effects meta-analysis was completed on the included outcome measures to estimate the treatment effect of interventions that included an activity tracker compared with a control group.
There was a significant increase in daily step count (standardized mean difference SMD 0.24; 95% CI 0.16 to 0.33; P<.001), moderate and vigorous physical activity (SMD 0.27; 95% CI 0.15 to 0.39; P<.001), and energy expenditure (SMD 0.28; 95% CI 0.03 to 0.54; P=.03) and a nonsignificant decrease in sedentary behavior (SMD -0.20; 95% CI -0.43 to 0.03; P=.08) following the intervention versus control comparator across all studies in the meta-analyses. In general, included studies were at low risk of bias, except for performance bias. Heterogeneity varied across the included meta-analyses ranging from low (I
=3%) for daily step count through to high (I
=67%) for sedentary behavior.
Utilizing a consumer-based wearable activity tracker as either the primary component of an intervention or as part of a broader physical activity intervention has the potential to increase physical activity participation. As the effects of physical activity interventions are often short term, the inclusion of a consumer-based wearable activity tracker may provide an effective tool to assist health professionals to provide ongoing monitoring and support.
•PD-L1 has emerged as an important cancer biomarker and target for immunotherapy in UC.•PD-L1 is frequently expressed on tumor cells and tumor-infiltrating immune cells.•Diagnostic assays are ...available, each with different scoring cutoffs to detect PD-L1.•Despite lack of assay standardization, PD-L1 expression can be reproducibly scored.•PD-L1 testing will increasingly guide treatment and should be discussed and offered to patients with UC.
Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway improve clinical outcomes in patients with locally advanced/metastatic urothelial carcinoma (UC). PD-L1 complementary or companion diagnostic assays are now available for anti–PD-1 and anti–PD-L1 antibodies and these assays enable testing at diagnosis. The role of PD-L1 testing in UC is, however, the subject of much discussion within the medical community, particularly in light of recent restrictions on recruitment of PD-L1–low patients in clinical trials of atezolizumab and pembrolizumab as first-line therapy, and the European Medicines Agency and US Food and Drug Administration limiting use of these agents as first-line therapy in cisplatin-ineligible patients to those with high PD-L1 expression. We explore the evolving evidence for PD-L1 expression testing in UC and the role of PD-L1 expression in both tumor cells and tumor-infiltrating immune cells. We review clinical data on the prognostic and predictive value of PD-L1 expression in response to anti–PD-1/PD-L1 agents as first- and second-line therapy, considering issues such as the differences among complementary diagnostic assays in terms of the type of cells scored, antibodies used, and cutoff values. We consider how PD-L1 testing fits into decision-making and the potential of emerging biomarkers in UC. We conclude that, based on the scientific rationale for its use and evidence from clinical trials, PD-L1 testing provides enriched information on the patients most likely to benefit from immune checkpoint blockade and should be routinely offered to patients with metastatic UC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Can the EU become a 'just' institution? Andrew Williams considers this highly charged political and moral question by examining the role of five salient values said to be influential in the ...governance and law of the Union: peace, the rule of law, respect for human rights, democracy, and liberty. He assesses each of these as elements of an apparent 'institutional ethos' and philosophy of EU law and finds that justice as a governing ideal has failed to be taken seriously in the EU. To remedy this condition, he proposes a new set of principles upon which justice might be brought more to the fore in the Union's governance. By focusing on the realisation of human rights as a core institutional value, Williams argues that the EU can better define its moral limits so as to evolve as a more just project.
The acute respiratory distress syndrome (ARDS) is a life-threatening lung condition resulting from direct and indirect insults to the lung. It is characterized by disruption of the ...endothelial-epithelial barrier, alveolar damage, pulmonary edema, and respiratory failure. A key feature of ARDS is the accumulation of neutrophils in the lung microvasculature, interstitium, and alveolar space. Despite a clear association between neutrophil influx into the lung and disease severity, there is some debate as to whether neutrophils directly contribute to disease pathogenesis. The primary function of neutrophils is to provide immediate host defense against pathogenic microorganisms. Neutrophils release numerous antimicrobial factors such as reactive oxygen species, proteinases, and neutrophil extracellular traps. However, these factors are also toxic to host cells and can result in bystander tissue damage. The excessive accumulation of neutrophils in ARDS may therefore contribute to disease progression. Central to neutrophil recruitment is the release of chemokines, including the archetypal neutrophil chemoattractant IL-8, from resident pulmonary cells. However, the chemokine network in the inflamed lung is complex and may involve several other chemokines, including CXCL10, CCL2, and CCL7. This review will therefore focus on the experimental and clinical evidence supporting neutrophils as key players in ARDS and the chemokines involved in recruiting them into the lung.
The effect of satellite mega-constellations on astronomical observations in the visible, near-infrared, and thermal infrared domains is estimated using a simple methodology, which is applied to ESO ...telescopes and instruments as examples (radio and (sub-)millimetre domains are not considered here). The study considers a total of 18 constellations in development by SpaceX, Amazon, OneWeb, and others, with over 26 thousand satellites, constituting a representative distribution. This study uses a series of simplifications and assumptions in order to obtain conservative, order-of-magnitude estimates of the effects: the satellites are assumed to be uniformly spread over the Earth’s globe, and their magnitude is estimated using a simplistic model calibrated on actual observations. The effect on various types of ground-based telescopic observations is estimated using a geometric probabilistic approach. The “trains” of very-low altitude satellites typically observed immediately after launch are extremely bright due to their very low orbit. They also fall very quickly in the shadow of the Earth after sunset. However, this initial bright state is not considered further, as the satellites quickly disperse into their higher altitude orbits. The number of illuminated satellites from the constellations above the horizon of an observatory ranges from approximately 1600 immediately after sunset, decreasing to 1100 at the end of astronomical twilight, most of them (∼85%) close to the horizon (below 30° of elevation). The large majority of these satellites will be too faint to be seen with the naked eye: at astronomical twilight, 260 would be brighter than magnitude 6 (i.e. visible in exceptional conditions), 110 brighter than 5 (i.e. visible in good conditions). Again, most of them (∼95%) will be close to the horizon (below 30° of elevation). The number of naked-eye satellites plummets as the Sun reaches 30−40° of elevation below the horizon. Specular flares and occultations by satellites are expected to cause only negligible effects on telescopic astronomical observations. The light trail caused by the satellite would ruin a small fraction (below the 1% level) of telescopic exposures using narrow to normal field imaging or spectroscopic techniques in the visible and near-infrared during the first and last hours of the night. Similarly, the thermal emission of the satellite would affect only a negligible fraction of the observations in the thermal infrared domain. However, wide-field exposures and long medium-field exposures would be affected at the 3% level during the first and last hours of the night. Furthermore, ultra-wide imaging exposures on a very large telescope (where saturation of the satellite trails has a ruinous effect on the detectors, such as those from the National Science Foundation’s
Vera C. Rubin
Observatory, formerly known as LSST), would be significantly affected, with 30–40% of such exposures being compromised during the first and last hours of the night. Coordination and collaboration between the astronomical community, satellite companies, and government agencies are therefore critical to minimise and mitigate the effect on astronomical observations, in particular on survey telescopes.
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The Blueprint Programmed Death Ligand 1 (PD-L1) Immunohistochemistry (IHC) Assay Comparison Project is an industrial-academic collaborative partnership to provide information on the analytical and ...clinical comparability of four PD-L1 IHC assays used in clinical trials.
A total of 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP142, and SP263), as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity. Clinical diagnostic performance was assessed through comparisons of patient classification above and below a selected expression cutoff and by agreement using various combinations of assays and cutoffs.
Analytical comparison demonstrated that the percentage of PD-L1–stained tumor cells was comparable when the 22C3, 28-8, and SP263 assays were used, whereas the SP142 assay exhibited fewer stained tumor cells overall. The variability of immune cell staining across the four assays appears to be higher than for tumor cell staining. Of the 38 cases, 19 (50.0%) were classified above and five (13%) were classified below the selected cutoffs of all assays. For 14 of the 38 cases (37%), a different PD-L1 classification would be made depending on which assay/scoring system was used.
The Blueprint PD-L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained. All of the assays demonstrated immune cell staining, but with greater variability than with tumor cell staining. By comparing assays and cutoffs, the study indicated that despite similar analytical performance of PD-L1 expression for three assays, interchanging assays and cutoffs would lead to “misclassification” of PD-L1 status for some patients. More data are required to inform on the use of alternative staining assays upon which to read different specific therapy-related PD-L1 cutoffs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Using model simulations, we demonstrate that the climate response to localized tropical sea surface temperature (SST) perturbations exhibits numerous non‐linearities. Most pronounced is an asymmetry ...in the response to positive and negative SST perturbations. Additionally, we identify a “magnitude‐dependence” of the response on the size of the SST perturbation. We then explain how these non‐linearities arise as a robust consequence of convective quasi‐equilibrium and weak (but non‐zero) temperature gradients in the tropical free‐troposphere, which we encapsulate in a “circus tent” model of the tropical atmosphere. These results demonstrate that the climate response to SST perturbations is fundamentally non‐linear, and highlight potential deficiencies in work which has assumed linearity in the response.
Plain Language Summary
Previous work has highlighted that Earth's energy balance is sensitive to the precise distribution of sea‐surface temperatures (SSTs), particularly in the tropical Pacific, with important implications for inferring climate sensitivity from the historical record. To quantify this “SST pattern effect,” many studies have adopted a linear framework where the climate response to an SST anomaly is assumed to be a linear function of the sign and size of the anomaly. Here, we show that this assumption is not applicable in many parts of the tropics, particularly the Central Pacific. We classify these non‐linearities into two classes and explain why they arise in terms of simple tropical dynamics. To summarize our findings we use a conceptual model of the tropical atmosphere which we term the “circus tent” model, which represents the dynamics behind these non‐linearities in an intuitive way. Our work suggests that previous work which has assumed linearity in the climate response to tropical SSTs may be suffering from compensating biases in their response.
Key Points
Contrary to assumptions made in previous work, we find that the climate response to tropical sea‐surface temperatures is highly non‐linear
These non‐linearities are most stark in the Central Pacific, and manifest even for very small perturbation magnitudes
Non‐linearity is a fundamental consequence of tropical dynamics, with important implications for prior work using linear Green's functions
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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