Abstract
The mean state, variability, and extreme variability of the stratospheric polar vortices, with an emphasis on the Northern Hemisphere (NH) vortex, are examined using two-dimensional moment ...analysis and extreme value theory (EVT). The use of moments as an analysis tool gives rise to information about the vortex area, centroid latitude, aspect ratio, and kurtosis. The application of EVT to these moment-derived quantities allows the extreme variability of the vortex to be assessed. The data used for this study are 40-yr ECMWF Re-Analysis (ERA-40) potential vorticity fields on interpolated isentropic surfaces that range from 450 to 1450 K.
Analyses show that the most extreme vortex variability occurs most commonly in late January and early February, consistent with when most planetary wave driving from the troposphere is observed. Composites around sudden stratospheric warming (SSW) events reveal that the moment diagnostics evolve in statistically different ways between vortex splitting events and vortex displacement events, in contrast to the traditional diagnostics. Histograms of the vortex diagnostics on the 850-K (~10 hPa) surface over the 1958–2001 period are fitted with parametric distributions and show that SSW events constitute the majority of data in the tails of the distributions. The distribution of each diagnostic is computed on various surfaces throughout the depth of the stratosphere; it shows that in general the vortex becomes more circular with higher filamentation at the upper levels. The Northern and Southern Hemisphere (SH) vortices are also compared through the analysis of their respective vortex diagnostics, confirming that the SH vortex is less variable and lacks extreme events compared to the NH vortex. Finally, extreme value theory is used to statistically model the vortex diagnostics and make inferences about the underlying dynamics of the polar vortices.
In many parts of the world including the Great Lakes region of North America, Cercospora leaf spot (CLS), caused by the fungal pathogen
, is a major foliar disease of sugar beet (
). Management of ...CLS involves an integrated approach which includes the application of fungicides. To guide fungicide application timings, disease prediction models are widely used by sugar beet growers in North America. While these models have generally worked well, they have not included information about pathogen presence. Thus, incorporating spore production and dispersal could make them more effective. The current study used sentinel beets to assess the presence of
spores in the environment early in the 2017 and 2018 growing seasons. Weather variables including air temperature, relative humidity, rainfall, leaf wetness, wind speed, and solar radiation were collected. These data were used to identify environmental variables that correlated with spore levels during a time when CLS is not generally observed in commercial fields.
spores were detected during mid-April both years, which is much earlier than previously reported. A correlation was found between spore data and all the weather variables examined during at least one of the two years, except for air temperature. In both years, spore presence was significantly correlated with rainfall (
< 0.0001) as well as relative humidity (
< 0.0090). Rainfall was particularly intriguing, with an adjusted R
of 0.3135 in 2017 and 0.1652 in 2018. Efforts are ongoing to investigate information on spore presence to improve prediction models and CLS management.
Bone marrow contains mesenchymal stem cells (MSCs) that can differentiate along multiple mesenchymal lineages. In this capacity they are thought to be important in the intrinsic turnover and repair ...of connective tissues while also serving as a basis for tissue engineering and regenerative medicine. However, little is known of the biological responses of human MSCs to inflammatory conditions. When cultured with IL-1β, marrow-derived MSCs from 8 of 10 human subjects deposited copious hydroxyapatite, in which authenticity was confirmed by Fourier transform infrared spectroscopy. Transmission electron microscopy revealed the production of fine needles of hydroxyapatite in conjunction with matrix vesicles. Alkaline phosphatase activity did not increase in response to inflammatory mediators, but PPi production fell, reflecting lower ectonucleotide pyrophosphatase activity in cells and matrix vesicles. Because PPi is the major physiological inhibitor of mineralization, its decline generated permissive conditions for hydroxyapatite formation. This is in contrast to MSCs treated with dexamethasone, where PPi levels did not fall and mineralization was fuelled by a large and rapid increase in alkaline phosphatase activity. Bone sialoprotein was the only osteoblast marker strongly induced by IL-1β; thus these cells do not become osteoblasts despite depositing abundant mineral. RT-PCR did not detect transcripts indicative of alternative mesenchymal lineages, including chondrocytes, myoblasts, adipocytes, ligament, tendon, or vascular smooth muscle cells. IL-1β phosphorylated multiple MAPKs and activated nuclear factor-κB (NF-κB). Certain inhibitors of MAPK and PI3K, but not NF-κB, prevented mineralization. The findings are of importance to soft tissue mineralization, tissue engineering, and regenerative medicine.
Background: The effects of inflammation upon the biology of human mesenchymal stem cells are poorly understood.
Results: IL-1β provoked massive hydroxyapatite deposition by inhibiting ectonucleotide pyrophosphatase. Cells did not express typical markers of osteoblasts or other mesenchymal lineages.
Conclusion: Inflammation promotes mineralization by a novel mechanism.
Significance: These data provide new insights into cytokine effects on mineralization of soft tissues.
Individuals with sickle cell disease (SCD) and sickle cell trait (SCT) have many risk factors that could make them more susceptible to COVID-19 critical illness and death compared to the general ...population. With a growing body of literature in this field, a comprehensive review is needed. We reviewed 71 COVID-19-related studies conducted in 15 countries and published between January 1, 2020, and October 15, 2021, including a combined total of over 2000 patients with SCD and nearly 2000 patients with SCT. Adults with SCD typically have a mild to moderate COVID-19 disease course, but also a 2- to 7-fold increased risk of COVID-19-related hospitalization and a 1.2-fold increased risk of COVID-19-related death as compared to adults without SCD, but not compared to controls with similar comorbidities and end-organ damage. There is some evidence that persons with SCT have increased risk of COVID-19-related hospitalization and death although more studies with risk-stratification and properly matched controls are needed to confirm these findings. While the literature suggests that most children with SCD and COVID-19 have mild disease and low risk of death, some children with SCD, especially those with SCD-related comorbidities, are more likely to be hospitalized and require escalated care than children without SCD. However, children with SCD are less likely to experience COVID-19-related severe illness and death compared to adults with or without SCD. SCD-directed therapies such as transfusion and hydroxyurea may be associated with better COVID-19 outcomes, but prospective studies are needed for confirmation. While some studies have reported favorable short-term outcomes for COVID-19 patients with SCD and SCT, the long-term effects of SARS-CoV-2 infection are unknown and may affect individuals with SCD and SCT differently from the general population. Important focus areas for future research should include multi-center studies with larger sample sizes, assessment of hemoglobin genotype and SCD-modifying therapies on COVID-19 outcomes, inclusion of case-matched controls that account for the unique sample characteristics of SCD and SCT populations, and longitudinal assessment of post-COVID-19 symptoms.
Purpose
The purpose of this study was to determine the cost-effectiveness of antibiotic-laden bone cement (ALBC) in primary total knee arthroplasty (TKA) from the perspective of a single-payer ...healthcare system.
Methods
A cost-utility analysis (CUA) was performed over a 2-year time horizon comparing primary TKA with either ALBC or regular bone cement (RBC) from the perspective of the single-payer Canadian healthcare system. All costs were in 2020 Canadian dollars. Health utilities were in the form of quality-adjusted life years (QALYs). Model inputs for cost, utilities and probabilities were derived from the literature as well as regional and national databases. One-way deterministic sensitivity analysis was performed.
Results
Primary TKA with ALBC was found to be more cost-effective compared to primary TKA with RBC with an incremental cost-effectiveness ratio (ICER) of -3,637.79 CAD/QALY. The use of routine ALBC remained cost-effective even with cost increases of up to 50% per bag of ALBC. TKA with ALBC was no longer cost-effective if the rate of PJI following this practice increased 52%, or the rate of PJI following the use of RBC decreased 27%.
Conclusions
The routine use of ALBC in TKA is a cost-effective practice in the single-payer Canadian healthcare system. This remains to be the case even with a 50% increase in the cost of ALBC. Policy makers and hospital administrators of single-payer healthcare systems can leverage this model to inform their local funding policies. Future prospective reviews and randomized controlled trials from the perspective of various healthcare models can further shed light on this issue.
Level of evidence
III.
•Proceedings from the ILSI-HESI Workshop on Cytokine Release, October 2013.•In vitro human cytokine release assays remain a priority for hazard ID for CRS.•Utility of cytokine release assays beyond ...hazard ID is an area of active research.•New assay approaches could lead to better translation of assay results to in vivo.
In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, “Workshop on Cytokine Release: State-of-the-Science, Current Challenges and Future Directions”. The workshop brought together scientists from pharmaceutical, academic, health authority, and contract research organizations to discuss novel approaches and current challenges for the use of in vitro cytokine release assays (CRAs) for the identification of cytokine release syndrome (CRS) potential of novel monoclonal antibody (mAb) therapeutics. Topics presented encompassed a regulatory perspective on cytokine release and assessment, case studies regarding the translatability of preclinical cytokine data to the clinic, and the latest state of the science of CRAs, including comparisons between mAb therapeutics within one platform and across several assay platforms, a novel physiological assay platform, and assay optimization approaches such as determination of FcR expression profiles and use of statistical tests. The data and approaches presented confirmed that multiple CRA platforms are in use for identification of CRS potential and that the choice of a particular CRA platform is highly dependent on the availability of resources for individual laboratories (e.g. positive and negative controls, number of human blood donors), the assay through-put required, and the mechanism-of-action of the therapeutic candidate to be tested. Workshop participants agreed that more data on the predictive performance of CRA platforms is needed, and current efforts to compare in vitro assay results with clinical cytokine assessments were discussed. In summary, many laboratories continue to focus research efforts on the improvement of the translatability of current CRA platforms as well explore novel approaches which may lead to more accurate, and potentially patient-specific, CRS prediction in the future.
Background It has been shown that addressing apical support at the time of hysterectomy for pelvic organ prolapse (POP) reduces recurrence and reoperation rates. In fact, national guidelines consider ...hysterectomy alone to be inadequate treatment for POP. Despite this, anterior and posterior colporrhaphy are frequently performed without a colpopexy procedure and hysterectomy alone is often utilized for treatment of prolapse. Objective The objectives of this study were to: (1) determine rates of concomitant procedures for POP in hysterectomies performed with POP as an indication, (2) identify factors associated with performance of a colpopexy at the time of hysterectomy for POP, and (3) identify the influence of surgical complexity on perioperative complication rates. Study Design This is a retrospective cohort study of hysterectomies performed for POP from Jan. 1, 2013, through May 7, 2014, in a statewide surgical quality database. Patients were stratified based on procedures performed: hysterectomy alone, hysterectomy with colporrhaphy and without apical suspension, and hysterectomy with colpopexy with or without colporrhaphy. Demographics, medical history and intraoperative care, and perioperative care were compared between the groups. Multivariable logistic regression models were created to identify factors independently associated with use of colpopexy and factors associated with increased rates of postoperative complications. Results POP was an indication in 1557 hysterectomies. Most hysterectomies were vaginal (59.6%), followed by laparoscopic or robotic (34.1%), and abdominal (6.2%). Hysterectomy alone was performed in 43.1% (95% confidence interval CI, 40.6–45.6) of cases, 32.8% (95% CI, 30.4–35.1) had a colporrhaphy without colpopexy, and 24.1% (95% CI, 22–26.3) had a colpopexy with or without colporrhaphy. Use of colpopexy was independently associated with patient age >40 years, POP as the only indication for surgery (odd ratio OR, 1.6; 95% CI, 1.185–2.230), laparoscopic surgery (OR, 3.2; 95% CI, 2.860–5.153), and a surgeon specializing in urogynecology (OR, 8.2; 95% CI, 5.156–12.923). The overall perioperative complication rate was 6.6%, with the majority being considered minor. Complications were more likely when the procedure was performed with an abdominal approach (OR, 2.3; 95% CI, 1.088–4.686), with the use of a colpopexy procedure (OR, 3.1; 95% CI, 1.840–5.194), and by a surgeon specializing in urogynecology (OR, 2.2; 95% CI, 1.144–4.315). Conclusion Colpopexy and colporrhaphy may be underutilized and are potential targets for quality improvement. Performance of additional procedures at the time of hysterectomy increased the rate of perioperative complications. Long-term consequences of these surgical practices deserve additional study.
Recent work has shown that the vertical structure of the Arctic polar vortex during different types of sudden stratospheric warming (SSW) events can be very distinctive. Specifically, SSWs can be ...classified into polar vortex displacement events or polar vortex splitting events. This paper aims to study the Arctic stratosphere during such events, with a focus on the stratopause using the Modern Era-Restrospective analysis for Research and Applications reanalysis data set. The reanalysis dataset is compared against two independent satellite reconstructions for validation purposes. During vortex displacement events, the stratopause temperature and pressure exhibit a wave-1 structure and are in quadrature whereas during vortex splitting events they exhibit a wave-2 structure. For both types of SSW the temperature anomalies at the stratopause are shown to be generated by ageostrophic vertical motions. Transformed Eulerian mean diagnostics are used to show differences in the planetary wave activity between displacement and splitting events. The convergence of Eliassen-Palm flux, which leads to SSWs is longer for displacement events and a persistent mesospheric Eliassen-Palm flux divergence can be observed about 20 days after displacement events. Finally, although this work focuses on the stratopause at high latitudes, associated observations of the equatorial middle atmosphere are also examined to explore links between the equator and polar evolution during SSWs.
Quantitative measurements of velocity for a low aspect ratio underexpanded elliptical jet are presented. Four jets at nozzle pressure ratios NPR = 2.2, 2.6, 3.4, 4.2 are studied for a smoothly ...contoured elliptical nozzle with an aspect ratio
a
/
b
= 2. High-resolution planar particle image velocimetry is used to extract information about the velocity fields and turbulent statistics. All four jets display the expected axis switching phenomenon, with the axis switching gaining strength with increasing pressure ratio. Evidence of regular reflection is seen for jets at pressure ratios of 2.6 and above. Measurements of fluctuating velocity indicate an oscillatory flapping mode in the minor axis plane for all but the highest pressure ratio. At the highest pressure ratio of NPR = 4.2, there is evidence of a cut-and-connect vortex bifurcation previously only observed for jets with higher aspect ratio.
The surface response to 11 year solar cycle variations is investigated by analyzing the long‐term mean sea level pressure and sea surface temperature observations for the period 1870–2010. The ...analysis reveals a statistically significant 11 year solar signal over Europe, and the North Atlantic provided that the data are lagged by a few years. The delayed signal resembles the positive phase of the North Atlantic Oscillation (NAO) following a solar maximum. The corresponding sea surface temperature response is consistent with this. A similar analysis is performed on long‐term climate simulations from a coupled ocean‐atmosphere version of the Hadley Centre model that has an extended upper lid so that influences of solar variability via the stratosphere are well resolved. The model reproduces the positive NAO signal over the Atlantic/European sector, but the lag of the surface response is not well reproduced. Possible mechanisms for the lagged nature of the observed response are discussed.
Key Points
11‐year solar signal detected over N. Atlantic/Europe
Signal is evident if data are lagged by ~3 years
HadGEM climate model simulates signal but not the lag
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