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Crime in progress : inside the Steele dossier and the Fusion GPS investigation of Donald Trump
\"The never-before-told inside story of the high-stakes, four-year-long investigation into Donald Trump's Russia ties--culminating in the Steele dossier, and sparking the Mueller report--from the founders of political opposition research company Fusion GPS\"-- From publisher's website.
Book
First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland
Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.
New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination.
Journal Article
Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas
Melanoma remains mostly an untreatable fatal disease despite advances in decoding cancer genomics and developing new therapeutic modalities. Progress in patient care would benefit from additional predictive models germane for human disease mechanisms, tumor heterogeneity, and therapeutic responses. Toward this aim, this review documents comparative aspects of human and naturally occurring canine melanomas. Clinical presentation, pathology, therapies, and genetic alterations are highlighted in the context of current basic and translational research in comparative oncology. Somewhat distinct from sun exposure-related human cutaneous melanomas, there is growing evidence that a variety of gene copy number alterations and protein structure/function mutations play roles in canine melanomas, in circumstances more analogous to human mucosal melanomas and to some extent other melanomas with murine sarcoma viral oncogene homolog B (BRAF), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS), and neurofibromin 1 tumor suppressor NF1 triple wild-type genotype. Gaps in canine genome annotation, as well as an insufficient number and depth of sequences covered, remain considerable barriers to progress and should be collectively addressed. Preclinical approaches can be designed to include canine clinical trials addressing immune modulation as well as combined-targeted inhibition of Rat Sarcoma Superfamily/Mitogen-activated protein kinase (RAS/MAPK) and/or Phosphatidylinositol-3-Kinase/Protein Kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signal transduction, pathways frequently activated in both human and canine melanomas. Future investment should be aimed towards improving understanding of canine melanoma as a predictive preclinical surrogate for human melanoma and for mutually benefiting these uniquely co-dependent species.
Journal Article
The Downward Influence of Stratospheric Sudden Warmings
The coupling between the stratosphere and the troposphere following two major stratospheric sudden warmings is studied in the Canadian Middle Atmosphere Model using a nudging technique by which the zonal-mean evolution of the reference sudden warmings are artificially induced in an ~100-member ensemble spun off from a control simulation. Both reference warmings are taken from a freely running integration of the model. One event is a displacement, the other is a split, and both are followed by extended recoveries in the lower stratosphere. The methodology permits a statistically robust study of their influence on the troposphere below. The nudged ensembles exhibit a tropospheric annular mode response closely analogous to that seen in observations, confirming the downward influence of sudden warmings on the troposphere in a comprehensive model. This tropospheric response coincides more closely with the lower-stratospheric annular mode anomalies than with the midstratospheric wind reversal. In addition to the expected synoptic-scale eddy feedback, the planetary-scale eddies also reinforce the tropospheric wind changes, apparently responding directly to the stratospheric anomalies. Furthermore, despite the zonal symmetry of the stratospheric perturbation, a highly zonally asymmetric near-surface response is produced, corresponding to a strongly negative phase of the North Atlantic Oscillation with a much weaker response over the Pacific basin that matches composites of sudden warmings from the Interim ECMWF Re-Analysis (ERA-Interim). Phase 5 of the Coupled Model Intercomparison Project models exhibit a similar response, though in most models the response’s magnitude is underrepresented.
Journal Article
Ubiquity of human-induced changes in climate variability
While climate change mitigation targets necessarily concern maximum mean state changes, understanding impacts and developing adaptation strategies will be largely contingent on how climate variability responds to increasing anthropogenic perturbations. Thus far Earth system modeling efforts have primarily focused on projected mean state changes and the sensitivity of specific modes of climate variability, such as the El Niño–Southern Oscillation. However, our knowledge of forced changes in the overall spectrum of climate variability and higher-order statistics is relatively limited. Here we present a new 100-member large ensemble of climate change projections conducted with the Community Earth System Model version 2 over 1850–2100 to examine the sensitivity of internal climate fluctuations to greenhouse warming. Our unprecedented simulations reveal that changes in variability, considered broadly in terms of probability distribution, amplitude, frequency, phasing, and patterns, are ubiquitous and span a wide range of physical and ecosystem variables across many spatial and temporal scales. Greenhouse warming in the model alters variance spectra of Earth system variables that are characterized by non-Gaussian probability distributions, such as rainfall, primary production, or fire occurrence. Our modeling results have important implications for climate adaptation efforts, resource management, seasonal predictions, and assessing potential stressors for terrestrial and marine ecosystems.
Journal Article
The minimal clinically important difference in the Oxford knee score and Short Form 12 score after total knee arthroplasty
Purpose
The aim of this study was to identify the minimal clinically important difference (MCID) in the Oxford knee score (OKS) and Short Form (SF-) 12 score after total knee arthroplasty (TKA).
Methods
Prospective pre-operative and 1 year post-operative OKS and SF-12 scores for 505 patients undergoing a primary TKA for osteoarthritis were collected during a one-year period. Patient satisfaction with their (1) patient relief and (2) functional outcome was used as the anchor questions. Their response to each question was recorded using a 5-point Likert scale: excellent, very well, well, fair, and poor. Simple linear regression was used to calculate the MCID for improvement in the OKS and physical component of the SF-12 score according to the level of patient satisfaction with their pain relief and function.
Results
The OKS improved by 15.5 (95 % CI 14.7–16.4) points and the SF-12 physical component score improved by 10.1 (95 % CI 9.1–11.2) points for the study cohort. The level of patient satisfaction with their pain relief and function correlated with the improvement in the OKS (
r
= 0.56;
p
< 0.001, and
r
= 0.56;
p
< 0.001) and the physical component of the SF-12 score (
r
= 0.51;
p
< 0.001, and
r
= 0.60;
p
< 0.001), respectively. The MCID for the OKS was 5.0 (95 % CI 4.4–5.5) and 4.3 (95 % CI 3.8–4.8) points and for the physical component of the SF-12, it was 4.5 (95 % CI 3.9–5.2) and 4.8 (95 % CI 4.2–5.4) points for pain relief and function, respectively.
Conclusion
The MCID identified for the OKS and SF-12 physical component score after TKA is the best available estimate and can be used to power studies and ensure that a statistical difference is also recognised by a patient.
Level of evidence
Retrospective diagnostic study, Level III.
Journal Article
Climate Variability and Change of Mediterranean-Type Climates
Mediterranean-type climates are defined by temperate, wet winters, and hot or warm dry summers and exist at the western edges of five continents in locations determined by the geography of winter storm tracks and summer subtropical anticyclones. The climatology, variability, and long-term changes in winter precipitation in Mediterranean-type climates, and the mechanisms for model-projected near-term future change, are analyzed. Despite commonalities in terms of location in the context of planetary-scale dynamics, the causes of variability are distinct across the regions. Internal atmospheric variability is the dominant source of winter precipitation variability in all Mediterranean-type climate regions, but only in the Mediterranean is this clearly related to annular mode variability. Ocean forcing of variability is a notable influence only for California and Chile. As a consequence, potential predictability of winter precipitation variability in the regions is low. In all regions, the trend in winter precipitation since 1901 is similar to that which arises as a response to changes in external forcing in the models participating in phase 5 of the Coupled Model Intercomparison Project. All Mediterranean-type climate regions, except in North America, have dried and the models project further drying over coming decades. In the Northern Hemisphere, dynamical processes are responsible: development of a winter ridge over the Mediterranean that suppresses precipitation and of a trough west of the North American west coast that shifts the Pacific storm track equatorward. In the Southern Hemisphere, mixed dynamic–thermodynamic changes are important that place a minimum in vertically integrated water vapor change at the coast and enhance zonal dry advection into Mediterranean-type climate regions inland.
Journal Article