Trends in Canada’s climate are analyzed using recently updated data to provide a comprehensive view of climate variability and long-term changes over the period of instrumental record. Trends in ...surface air temperature, precipitation, snowcover, and streamflow indices are examined along with the potential impact of low-frequency variability related to large-scale atmospheric and oceanic oscillations on these trends. The results show that temperature has increased significantly in most regions of Canada over the period 1948–2012, with the largest warming occurring in winter and spring. Precipitation has also increased, especially in the north. Changes in other climate and hydroclimatic variables, including a decrease in the amount of precipitation falling as snow in the south, fewer days with snow cover, an earlier start of the spring high-flow season, and an increase in April streamflow, are consistent with the observed warming and precipitation trends. For the period 1900–2012, there are sufficient temperature and precipitation data for trend analysis for southern Canada (south of 60°N) only. During this period, temperature has increased significantly across the region, precipitation has increased, and the amount of precipitation falling as snow has decreased in many areas south of 55°N. The results also show that modes of low-frequency variability modulate the spatial distribution and strength of the trends; however, they alone cannot explain the observed long-term trends in these climate variables.
Summary In the past 10 years, there has been a lot of enthusiasm surrounding the use of serum hepatitis B surface antigen (HBsAg) quantification to predict disease activity and monitor treatment ...response in chronic hepatitis B. The measurement of HBsAg levels have been standardized in IU/ml, and nowadays it is almost a mandatory measurement due to the development of new antiviral treatments aiming at HBsAg seroclearance, i.e., functional cure of hepatitis B. Recently, there has been an improved understanding of the molecular virology of HBsAg, and particularly the relative roles of covalently closed circular DNA and integrated hepatitis B virus (HBV) DNA. This has shed new light on the interpretation of HBsAg levels in different phases of chronic hepatitis B. HBsAg level can assist the differentiation of immune tolerance and immune clearance in hepatitis B e antigen (HBeAg)-positive patients, and it can predict inactive disease and spontaneous HBsAg seroclearance in HBeAg-negative patients. The determination of HBsAg level is pivotal to individualize pegylated interferon (PegIFN) treatment; it is the key investigation to decide early termination of PegIFN among non-responders. Among patients treated by nucleos(t)ide analogues, responders tend to have dramatic reduction of HBsAg to low levels, which may be followed by HBsAg seroclearance. With newer data on combination treatment of PegIFN and nucleos(t)ide analogues as well as emerging new antiviral agents, HBsAg quantification is expected to become increasingly important to monitor and guide antiviral therapy for chronic hepatitis B.
In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies ...involving critically ill children who have not undergone cardiac surgery are lacking.
In a 35-center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower-target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher-target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)-free days to day 28.
The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower-target group and 353 to the higher-target group. In the intention-to-treat analysis, the median number of ICU-free days did not differ significantly between the lower-target group and the higher-target group (19.4 days interquartile range {IQR}, 0 to 24.2 and 19.4 days IQR, 6.7 to 23.9, respectively; P=0.58). In per-protocol analyses, the median time-weighted average glucose level was significantly lower in the lower-target group (109 mg per deciliter IQR, 102 to 118; 6.1 mmol per liter IQR, 5.7 to 6.6) than in the higher-target group (123 mg per deciliter IQR, 108 to 142; 6.8 mmol per liter IQR, 6.0 to 7.9; P<0.001). Patients in the lower-target group also had higher rates of health care-associated infections than those in the higher-target group (12 of 349 patients 3.4% vs. 4 of 349 1.1%, P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients 5.2% vs. 7 2.0%, P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator-free days.
Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF-PINT ClinicalTrials.gov number, NCT01565941 .).
In this study, we present the collation and analysis of the gridded land‐based dataset of indices of temperature and precipitation extremes: HadEX2. Indices were calculated based on station data ...using a consistent approach recommended by the World Meteorological Organization (WMO) Expert Team on Climate Change Detection and Indices, resulting in the production of 17 temperature and 12 precipitation indices derived from daily maximum and minimum temperature and precipitation observations. High‐quality in situ observations from over 7000 temperature and 11,000 precipitation meteorological stations across the globe were obtained to calculate the indices over the period of record available for each station. Monthly and annual indices were then interpolated onto a 3.75° × 2.5° longitude‐latitude grid over the period 1901–2010. Linear trends in the gridded fields were computed and tested for statistical significance. Overall there was very good agreement with the previous HadEX dataset during the overlapping data period. Results showed widespread significant changes in temperature extremes consistent with warming, especially for those indices derived from daily minimum temperature over the whole 110 years of record but with stronger trends in more recent decades. Seasonal results showed significant warming in all seasons but more so in the colder months. Precipitation indices also showed widespread and significant trends, but the changes were much more spatially heterogeneous compared with temperature changes. However, results indicated more areas with significant increasing trends in extreme precipitation amounts, intensity, and frequency than areas with decreasing trends.
Key Points
We present the most comprehensive land‐based gridded dataset of climate extremes
Temperature extremes show consistent warming trends over the past century
Precipitation extremes are increasing in more areas than they are decreasing
A workshop on climate change indices was held at the Mauritius Meteorological Services in October 2009 to produce the first analysis of climate trends for the countries of the western Indian Ocean. ...Scientists brought their long‐term daily temperature and precipitation for a careful assessment of data quality and homogeneity, and for the preparation of climate change indices. This paper reports on the trends in daily and extreme temperature and precipitation indices for 1961–2008. The results indicate a definitive warming of surface air temperature at land stations. Annual means of the daytime and nighttime temperatures have increased at a similar rate, leading to no discernible change in the diurnal temperature range. Significant increasing trends were found in the frequency of warm days and warm nights, while decreasing trends were observed in the frequency of cold days and cold nights. Moreover, it seems that the warm extremes have changed more than the cold extremes in the western Indian Ocean region. Trends in precipitation indices are generally weak and show less spatial coherence. Regionally, a significant decrease was found in the annual total rainfall for the past 48 years. The results also show some increase in consecutive dry days, no change in daily intensity and consecutive wet days, and a decrease in extreme precipitation events. Temperature indices are highly correlated with sea surface temperatures of the region, whereas weak correlations are found with the precipitation indices.
Key Points
A workshop on climate change indices was held in Mauritius
This paper reports on trends in daily and extremes temperature and indices
The results show a warming and no strong evidence of change in precipitation
A weeklong workshop in Brazil in August 2004 provided the opportunity for 28 scientists from southern South America to examine daily rainfall observations to determine changes in both total and ...extreme rainfall. Twelve annual indices of daily rainfall were calculated over the period 1960 to 2000, examining changes to both the entire distribution as well as the extremes. Maps of trends in the 12 rainfall indices showed large regions of coherent change, with many stations showing statistically significant changes in some of the indices. The pattern of trends for the extremes was generally the same as that for total annual rainfall, with a change to wetter conditions in Ecuador and northern Peru and the region of southern Brazil, Paraguay, Uruguay, and northern and central Argentina. A decrease was observed in southern Peru and southern Chile, with the latter showing significant decreases in many indices. A canonical correlation analysis between each of the indices and sea surface temperatures (SSTs) revealed two large-scale patterns that have contributed to the observed trends in the rainfall indices. A coupled pattern with ENSO-like SST loadings and rainfall loadings showing similarities with the pattern of the observed trend reveals that the change to a generally more negative Southern Oscillation index (SOI) has had an important effect on regional rainfall trends. A significant decrease in many of the rainfall indices at several stations in southern Chile and Argentina can be explained by a canonical pattern reflecting a weakening of the continental trough leading to a southward shift in storm tracks. This latter signal is a change that has been seen at similar latitudes in other parts of the Southern Hemisphere. A similar analysis was carried out for eastern Brazil using gridded indices calculated from 354 stations from the Global Historical Climatology Network (GHCN) database. The observed trend toward wetter conditions in the southwest and drier conditions in the northeast could again be explained by changes in ENSO.
Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers ...may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.
In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.
A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval CI, 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.
Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).
Circumpolar rivers, including the Mackenzie River in Canada, are sources of the contaminant mercury (Hg) to the Arctic Ocean, but few Hg export studies exist for these rivers. During the 2007–2010 ...freshet and open water seasons, we collected river water upstream and downstream of the Mackenzie River delta to quantify total mercury (THg) and methylmercury (MeHg) concentrations and export. Upstream of the delta, flow-weighted mean concentrations of bulk THg and MeHg were 14.6 ± 6.2 ng L–1 and 0.081 ± 0.045 ng L–1, respectively. Only 11–13% and 44–51% of bulk THg and MeHg export was in the dissolved form. Using concentration–discharge relationships, we calculated bulk THg and MeHg export into the delta of 2300–4200 kg yr–1 and 15–23 kg yr–1 over the course of the study. Discharge is not presently known in channels exiting the delta, so we assessed differences in river Hg concentrations upstream and downstream of the delta to estimate its influence on Hg export to the ocean. Bulk THg and MeHg concentrations decreased 19% and 11% through the delta, likely because of particle settling and other processes in the floodplain. These results suggest that northern deltas may be important accumulators of river Hg in their floodplains before export to the Arctic Ocean.
Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most ...critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Serum hepatitis B surface antigen (HBsAg) levels may reflect the immunomodulatory efficacy of pegylated interferon (PEG‐IFN). We investigated within a large randomized trial whether quantitative ...HBsAg levels predict response to PEG‐IFN in patients with hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B. Serum HBsAg was measured in samples taken at baseline and weeks 4, 8, 12, 24, 52, and 78 of 221 patients treated with PEG‐IFN alfa‐2b with or without lamivudine for 52 weeks. HBsAg decline was compared between treatment arms and between responders and nonresponders. Response was defined as HBeAg loss with HBV DNA < 10,000 copies/mL at 26 weeks after treatment (week 78); 43 of 221 (19%) patients achieved a response. One year of PEG‐IFN with or without lamivudine resulted in a significant decline in serum HBsAg, which was sustained after treatment (decline 0.9 log IU/mL at week 78, P < 0.001). Patients treated with combination therapy experienced a more pronounced on‐treatment decline, but relapsed subsequently. Responders experienced a significantly more pronounced decline in serum HBsAg compared to nonresponders (decline at week 52: 3.3 versus 0.7 log IU/mL, P < 0.001). Patients who achieved no decline at week 12 had a 97% probability of nonresponse through posttreatment follow‐up and no chance of HBsAg loss. In a representative subset of 149 patients similar results were found for prediction through long‐term (mean 3.0 years) follow‐up. Conclusion: PEG‐IFN induces a significant decline in serum HBsAg in HBeAg‐positive patients. Patients who experience no decline from baseline at week 12 have little chance of achieving a sustained response and no chance of HBsAg loss and should be advised to discontinue therapy with PEG‐IFN. (HEPATOLOGY 2010)
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