Well-designed monitoring approaches are needed to assess effects of industrial development on downstream aquatic environments and guide environmental stewardship. Here, we develop and apply a monitoring approach to detect potential enrichment of metals concentrations in surficial lake sediments of the Peace-Athabasca Delta (PAD), northern Alberta, Canada. Since the ecological integrity of the PAD is strongly tied to river floodwaters that replenish lakes in the delta, and the PAD is located downstream of the Alberta oil sands, concerns have been raised over the potential transport of industry-supplied metals to the PAD via the Athabasca River. Surface sediment samples were collected in September 2017 from 61 lakes across the delta, and again in July 2018 from 20 of the same lakes that had received river floodwaters 2 months earlier, to provide snapshots of metals concentrations  that have recently accumulated in these lakes. To assess for anthropogenic enrichment, surficial sediment metals concentrations were normalized to aluminum and compared to pre-industrial baseline  metal-aluminum linear relations for the Athabasca and Peace sectors of the PAD developed from pre-1920 measurements in lake sediment cores. Numerical analysis demonstrates no marked enrichment of these metals concentrations above pre-1920 baselines despite strong ability (> 99% power) to detect enrichment of 10%. Measurements of river sediment collected by the Regional Aquatics- and Oil Sands-Monitoring Programs (RAMP/OSM) also did not exceed pre-1920 concentrations. Thus, results presented here show no evidence of substantial oil sands-derived metals enrichment of sediment supplied by the Athabasca River to lakes in the PAD and demonstrate the usefulness of these methods as a monitoring framework.The online version of this article (10.1007/s10661-020-8067-y) contains supplementary material, which is available to authorized users. As large-scale mining operations continue to expand across northern Canada, so do concerns about releases of contaminants and their effects on downstream aquatic ecosystems (Schindler and Smol In northern Alberta (Canada), local, national, and international concerns have been raised about environmental consequences of contaminant releases from oil sands mining and processing activities to the Athabasca River and, at its terminus, the Peace-Athabasca Delta (PAD). The PAD is one of the world’s largest inland freshwater deltas, and its abundant shallow lakes provide habitat for a variety of biota and resources that support indigenous communities based in Fort Chipewyan. Mostly protected within the boundaries of Wood Buffalo National Park (WBNP), the PAD has gained recognition as a Ramsar Wetland of International Importance and contributed to the listing of WBNP as a UNESCO World Heritage Site for its historical, ecological, and cultural significance. Shallow lakes dominate this landscape and are largely dependent on periodic ice-jam flood events that occur along the Peace and Athabasca rivers to maintain their water balances PADPG . AlthougIt has remained challenging to assess the extent of metals enrichment at the PAD because systematic monitoring in the Lower Athabasca Oil Sands Region by the industry-funded Regional Aquatics Monitoring Program (RAMP) was not initiated until 1997—three decades after the start of oil sands production  baselines derived from analyses of sediment cores from two floodplain lakes, Wiklund et al.  assessedThe objective of this study is to assess metals concentrations in recently deposited sediment in a large suite of flood-prone lakes from the PAD for evidence of enrichment using baseline metals concentrations established from the analysis of pre-1920 sediments in cores from six lakes. To accomplish this, surface sediment was sampled in 2017 from 61 lakes, which span the hydrological gradient of lake water balance conditions across the Peace and Athabasca sectors of the PAD  and black shale polymetallic deposits  near the town of Peace River, Alberta Rukhlov . The Pea~ 0.07 km and ~ 0.2 km, respectively, from Mamawi Creek, a distributary that conveys Athabasca and Embarras river flow  Laboratory with the use of an Ortec co-axial HPGe Digital Gamma Ray Spectrometer (Ortec #GWL-120-15). Select 1-cm sediment intervals were freeze-dried and loaded into pre-weighed SARSTEDT polypropylene tubes to a height of 3.5 cm. The tubes were capped with a silicone disc, epoxy resin, and left for a minimum of 21 days, allowing 3 and HCl) which liberates metals that may be environmentally available  were submitted to ALS Canada Ltd.  for metals analysis following the method EPA 200.2/6020A, a partial digestion  were used to quantify the degree of enrichment of metals concentrations in surface sediment of lakes in the PAD collected in September 2017 and July 2018, relative to pre-1920 baseline metals concentrations. EFs are expressed as a ratio of the measured Al-normalized metal concentrations to the metal concentration that is expected based on its pre-1920 relationship with the normalizing agent (Al). Thus, an EF of 1.0 identifies no enrichment above baseline and EF of 2.0 identifies a doubling of metal concentration above baseline. Boxplots were used to present the distribution of EFs graphically.p values, post-hoc tests  were conducted to determine pairwise differences among the groups. To address the goals of this study, we focus on reporting results where there was significant enrichment above the pre-1920 baseline. The one-way ANOVA and post-hoc tests were performed using IBM-SPSS Statistics version 25.A series of one-way analysis of variance (ANOVA) tests were conducted to determine if mean EF values differ significantly among the pre-1920 baseline samples, lake surface sediment samples collected in 2017 and lake surface sediment samples collected in 2018. For each metal, ANOVA tests were run separately for sites in the Peace sector and sites in the Athabasca sector. For tests which resulted in significant To determine ability of the PAD lake surface sediment metals concentration data sets to detect a rise in metal EF values above the pre-1920 baseline, we ran a series of power analyses  to (1) determine the minimum rise in EF  that can be detected above an EF of 1.00 with 90% power and (2) calculate the power to detect a 10% rise in EF . The power analyses were run as one-sample tests at alpha = 0.05 and were one-tailed.210Pb activity profiles in lake sediment cores from four lakes  show a relatively consistent decline of activity with depth. Background  210Pb activity for these four lakes was reached between 16 and 33 cm indicating variable sedimentation rates among lakes. For these lakes, pre-1920 sediments occur below 19, 32, 27, and 21 cm for PAD 32, M7, PAD 65, and PAD 67, respectively. Lakes PAD 30 and PAD 31 display different 210Pb activity profiles with low activity at the bottom of the core, a rise in activity at mid-depth, and a decline in the upper sections of the cores , between the metals of interest  and Al were developed, where possible, from measurements of the metals concentrations in pre-1920 sediment for the Peace and Athabasca sectors Fig. . AnalyseBased on heterogeneity of slopes tests, slopes of all metal-Al relations are significantly steeper for the pre-1920 Peace sector regressions than those for the Athabasca sector Tables ; Fig. 3.Surficial lake sediment metals concentrations from 2017 Fig.  and 2018Similar patterns are evident for the metals concentrations in the 2018 flood-supplied surface sediment samples Fig. . All meaRiver-bottom sediment metals concentrations measured in the Athabasca Delta by RAMP and OSM were assessed on pre-1920 baselines defined from Athabasca sector lake sediment cores, which include Be, Cr, Pb, V, and Zn Fig. . The majEnrichment factors (EF) were calculated as a means of quantifying and summarizing metals concentrations in recently deposited lake sediments relative to the natural range of variability captured by the pre-1920 baseline samples Fig. . For mosAt the Athabasca sector, there are a few instances of significantly higher mean metals EFs in 2017 and/or 2018 surficial lake sediments relative to the pre-1920 baseline values, but the mean differences are < 0.15  are not adequately characterized for river-bottom sediment. Since many RAMP/OSM metals concentrations plot below the pre-1920 regression lines, most of the EF interquartiles (25–75th percentile) are below 1.0, the implications of which are discussed further below.Use of floodplain lake sediment cores to establish sector-specific pre-1920 baseline metals concentrations in the PADLack of knowledge of the natural range of variation in sediment metals concentrations has long hampered ability to accurately assess for evidence of metals enrichment in the Athabasca River by oil sands operations  possess concentrations above CCME ISQG in both the 2017 and 2018 datasets for the Peace sector, metals concentrations indeed fall within the range of natural variation defined for the sediment conveyed by the Peace River. Geological deposits listed above provide just a few of the potential sources that may lead to differences in the observed metals concentrations in lake sediment supplied by the Peace and Athabasca rivers. Further analysis of source contribution of metals upstream is required to more fully explain the differing metal-Al relations observed in this study.The six collective lake sediment cores used to establish pre-1920 baseline metals concentrations span a broad range  of Al concentrations used to characterize metal-Al relations in lake sediment Fig. . This ra2 PAD. The 2017 dataset included ~ 1 cm thick surficial sediments obtained from 61 lakes that span the full range of hydrological conditions .Vanadium was scrutinized because it has been identified as an oil sands indicator metal for contamination  in the RAMP/OSM samples (2000–2015), there are challenges to interpreting these results. Our assessments of enrichment of the RAMP/OSM data are inhibited by what appears to be steeper metal-Al relations at the low Al concentrations typical of river-bottom sediment, which are outside the range of our lake-derived pre-1920 baseline concentrations. This would imply that our baselines for the lower Al concentrations may be over-estimating natural river-bottom metals concentrations , which is evident for many of the metals. Clearly, these results demonstrate that baselines constructed from lake sediment in this study are best applied to lake sediment accumulated after industrial development, as opposed to the unknown time-frame represented by river-bottom sediment. Therefore, we advocate that sampling the fine-grained fraction of flood sediment deposited into floodplain lakes is a more sensitive, real-time approach for assessing metals concentrations of river-derived suspended sediment.Scientific research is needed to inform environmental monitoring, and here, clearly defined research objectives have provided direction for future aquatic monitoring efforts using sediment from floodplain lakes in the PAD. In the absence of long-term monitoring data, the use of paleolimnological approaches has demonstrated to be an effective method in characterizing natural concentrations of metals in sediments from flood-prone lakes, which are required to assess contemporary metals concentrations


Studies in high-income settings have shown association between Cytomegalovirus (CMV) infection and adverse cardiovascular outcome, especially in HIV infection. We aimed to study the association between serum concentration of anti-CMV IgG and ischaemic stroke in HIV-infected Malawians.Our sample was derived from a case-control stroke study in Malawi. Serum concentration of anti-CMV IgG was measured using enzyme-linked immunosorbent assay. Multivariable logistic regression was used to study the association between high concentrations of anti-CMV IgG (above the third tertile) and ischaemic stroke while adjusting for cardiovascular risk factors.3 (IQR: [75–278] and [230–533]) in cases and controls, respectively. High concentration of anti-CMV IgG was associated with ischaemic stroke in the univariable model (OR = 2.56 [1.23–5.34]) but not after adjusting for duration of antiretroviral therapy (ART), CD4+ count, and other cardiovascular risk factors (OR = 0.94 [0.29–3.08]). Low CD4+ count was an independent predictor of stroke. There was a negative correlation between serum concentration of anti-CMV IgG and CD4+ count .Overall, 139 HIV-positive adults  were included. The median CD4+ count was 136 and 401 cell/mmHigh concentration of anti-CMV IgG is not independently associated with ischaemic stroke in HIV-infected Malawians. Larger cohort studies are needed to further investigate the role of humoral response to CMV in the pathophysiology of HIV-associated stroke. Stroke is a global problem but increasing disproportionately in low-to-middle income countries. This is largely the consequence of lifestyle changes and aging of the population. HIV infection, which is prevalent in sub-Saharan Africa, contributes to young strokes, and further compounds the stroke burden. Early initiation of antiretroviral therapy (ART) has been shown to reduce the overall risk of stroke . HoweverIn Africa, the prevalence of CMV infection is high, ranging from 81.8% in HIV-negative adults to 94.8% in HIV-positive adults , 9. A feDrugs to prevent CMV reactivation such as Valganciclovir and newer agents such as Letermovir are available and could eventually be offered to reduce the risk of stroke in HIV-infected individuals if the association between stroke and CMV reactivation is demonstrated throughout the different stages of HIV infection and across the spectrum of cardiovascular disease –15. In tOur sample was derived from a case-control stroke study in Malawi which recruited 222 stroke cases and 503 controls within the community of Blantyre from 2011 to 2012  of whom 31.3% (5/16) had a serum anti-CMV IgG concentration greater than the third tertile of the distribution in the study population.The serum concentration of anti-CMV IgG was considered high when greater than the third tertile of the distribution in the entire sample (18.94 IU/ml). There were 47 patients (33.8%) with a high serum concentration of anti-CMV IgG including 23 cases and 24 controls. The mean serum concentration of anti-CMV IgG in this subgroup is given in Table 2). Low CD4+ count, prior history of cerebrovascular event, and abdominal obesity were independent predictors of stroke (Table 2). Using the serum concentration of anti-CMV IgG as a continuous variable in the logistic regression model did not significantly modify the associations reported. There was no interaction between high concentration of anti-CMV IgG and ART status or the CD4+ count.Although high concentration of anti-CMV IgG was significantly associated with stroke in the univariable logistic regression analysis , the significance was lost after adjusting for duration of ART, CD4+ count, and other classical risk factors of stroke   as pictured in We sought to assess the relationship between serum concentration of anti-CMV IgG and stroke in HIV-positive Malawian adults. Our sample included 139 participants (48 ischaemic stroke cases and 91 controls) who were all CMV-positive and represents the largest cohort of HIV-infected stroke patients investigating this question thus far. We found that high concentration of anti-CMV IgG was not an independent risk factor for stroke in contrast to low CD4+ count, prior history of stroke or TIA, and abdominal obesity. A negative correlation was found between the serum concentration of anti-CMV IgG and the CD4+ count (patients with higher concentrations of antibodies had a lower CD4+ count) suggesting that HIV-associated immunosuppression favours CMV reactivation thus leading to a sustained cellular and humoral response that might result in an increased risk of stroke.There is evidence that high concentration of anti-CMV IgG is a good marker of subclinical CMV reactivation driven by immunosuppression, and correlates well with inflammation, cardiovascular disease and mortality , 17, 18.The negative impact of CMV reactivation on the immune system can also impair the host’s ability to mount a balanced reconstitution of the immune system following ART initiation . This coOur study was not large enough to confidently prove an independent association between CMV reactivation and stroke. While the pathophysiological hypotheses discussed above are biologically plausible, we were unable to confirm whether CMV reactivation is a mediator on the pathway from HIV infection to stroke or an innocent bystander. However, there is evidence to suggest that immune response to CMV rather than the direct effect of viral replication is responsible for the adverse clinical outcome seen in many studies . TherefoThis is the first study to explore the relationship between stroke and serum concentration of anti-CMV IgG in HIV-infected patients, in an African setting . However, the small sample size provided insufficient power to detect an independent association between high concentration of anti-CMV IgG or recent ART initiation and stroke. Moreover, our estimation of the serum concentration of anti-CMV antibodies could be improved by multiple sampling. We also acknowledge that more specific methods to assess CMV reactivation (e.g. plasma CMV DNA load and CMV-specific T-cell response) –27 couldIn conclusion, this study suggests that, in individuals with advanced HIV infection, high serum concentration of anti-CMV IgG is not independently associated with stroke. However, it is associated with immunosuppression, which is an independent risk factor for stroke, and thus might have a mediating role. Further cohort studies with larger sample size are needed to clarify the contribution of CMV reactivation to the short- and long-term risk of stroke in HIV-infected individuals before advocating the use of specific anti-CMV drugs for primary prevention. Such studies should combine rigorous clinical and CMV-specific laboratory tools for accurate diagnosis of CMV reactivation and assess the contribution of other herpesviruses to the chronic inflammation observed in HIV-infected individuals. They should also aim to include a greater number of patients initiating ART (representing only 14.7% of our sample) to test the hypothesis that the potential mediating role of CMV reactivation in the pathophysiology of HIV-associated stroke is important at the time of immune reconstitution in people with low baseline CD4+ counts.S1 Appendix(DTA)Click here for additional data file.


We examined whether baseline self-reported physical activity is associated with the efficacy of cognitive behavioral therapy for insomnia (CBT-I) in older veterans. Community-dwelling veterans aged 60 years and older with insomnia received CBT-I in a randomized controlled trial. Participants who received active treatment were divided into low and high physical activity based on self-report. Sleep outcomes were measured by sleep diary, questionnaire and wrist actigraphy; collected at baseline, post-treatment, 6-month and 12-month follow-up. Mixed-effects models compared differences between physical activity groups in change in sleep outcome from baseline to each follow-up, and equivalence tests examined if physical activity groups were clinically equal. There were no significant differences in sleep outcomes between physical activity groups. Equivalence tests suggested possible equality in physical activity groups for five of seven sleep outcomes. Efficacy of CBT-I in older veterans was not associated with self-reported physical activity at baseline. Older adults with insomnia who report low levels of physical activity can benefit from CBT-I. Aging is associated with both an increased prevalence of insomnia  has been shown to be highly effective for treatment of chronic insomnia in a variety of populations, including among older adults  may also be used. Taken together, CBT-I commonly involves approaches such as: (1) decreasing excessive time in bed awake; (2) limiting naps, which can impair the sleep drive, and increasing daytime alertness via increased daytime activity and light exposure; (3) re-establishing the association between the bed and sleep; (4) decreasing disruptive stimuli in the sleep environment; (5) improving general sleep habits; and (6) rectifying incorrect beliefs about sleep  whether low baseline physical activity among participants who received CBT-I impacts the efficacy of the CBT-I intervention; and (b) whether older adults with high vs. low baseline physical activity display clinically equivalent CBT-I outcomes. We hypothesized that: (a) low baseline physical activity would indeed impact the efficacy of CBT-I; and (b) participants who had higher levels of baseline physical activity would have better sleep outcomes compared to those who had lower levels of baseline physical activity; in other words we expected sleep effects of CBT-I in older adults with high vs. low baseline physical activity levels would not be clinically equivalent.This study involved secondary analysis of data from the treatment group of a randomized controlled trial comparing CBT-I  with a general sleep education control. The active treatment involved typical components of CBT-I ; it was not an exercise intervention. Participants were randomized to receive CBT-I in either a small group or individual format, or to the control condition. The main study findings and study methods have been previously described .In this current secondary analysis, we focused on findings among participants who were randomized to receive CBT-I, excluding participants who were randomized to receive the control condition. Specifically, we categorized these treatment group participants based on their self-reported baseline physical activity. Physical activity was measured based on the participant’s response to a query regarding their frequency of physical activity in a typical week. CBT-I treatment results for individuals who stated that they participated in physical activity on most days (four or more) during a typical week were compared to treatment results of those who stated that they participated in physical activity three or fewer days per week .Participants were recruited among outpatient veterans who had visited an urban VA healthcare system in the prior 18 months and who lived within 30 miles of the facility. Potential participants were identified from the VA national data warehouse and were mailed a 25-item survey to identify those with evidence of insomnia disorder according to ICSD-2 criteria. Respondents who met ICSD-2 diagnostic criteria for insomnia based on the survey, who reported their sleep problems were present for 3 months or longer, and who were willing to be contacted for research purposes were assessed by trained research staff for study eligibility by phone. Participants were excluded if they were unable or unwilling to participate in person, if they reported a diagnosis of sleep apnea or they screened positive for sleep apnea (defined by an apnea-hypopnea index of 20 or greater) in ambulatory testing performed as part of the research assessment process, or if they had severe medical or psychiatric illness  were placed into the high physical activity group, whereas subjects who responded 3 days or fewer were placed into the low physical activity group  and objectively (using wrist actigraphy). Participants completed structured sleep questionnaires (which were collected by trained research staff in participant interviews) and 7-day sleep diaries (which were completed by participants at home and brought in for review by research staff) at baseline and all follow-up time points . The change in the following subjective sleep outcome measures obtained via questionnaires and sleep diaries was used to determine the efficacy of the CBT-I treatment: (1) sleep onset latency in minutes ); (2) diary wake after sleep onset (WASO-D) in minutes, which was the number of minutes the participant was awake during the night after falling asleep; (3) diary total wake time (TWT-D) at night in minutes, which was the total number of minutes awake between bedtime and rise time the next morning; and (4) sleep efficiency (which was the time asleep over the time in bed between bedtime and rise time the next morning) expressed as a percent , all based on sleep diaries; (5) the PSQI , and time was a four-level repeated-measures factor . When used for repeated-measures designs, mixed-effects models allow for incomplete data for certain time points . Differences between physical activity groups at baseline were evaluated using two-sample a priori. The equivalence tests were run to determine if the mean and 95% confidence interval for the difference between the physical activity groups in their changes from baseline for each sleep measure and to each time point  were within pre-specified clinical significance thresholds. Clinical significance thresholds defined the difference in change needed between the two groups for them to be considered clinically different. If the confidence interval is completely within the threshold, then there is a high degree of certainty that the two groups are clinically the same. On the other hand, when the confidence interval overlaps the threshold, this does not prove differences between the groups. For this analysis, two thresholds of clinical significance were used  to account for possible variation in clinical significance for CBT-I. For actigraphy and diary measures, a numeric value  was established for each threshold. For PSQI and ISI, thresholds were calculated using an effect size of 0.8 for the large threshold (large effect size) and 0.4  for the small threshold , and 60 (56.6%) reported 4 days of physical activity per week or more . As shown in Table P = 0.049), scored higher on the SF-12 Physical Composite Subscale , was more likely to have had sleep problems for 12 or more months (P = 0.02), was more likely to have less than a high school education (P = 0.04), was less likely to be divorced/separated (P = 0.001), and had fewer comorbidities (P = 0.02).Among the 106 participants randomized to active treatment , 46 (43.4%) reported 3 days of physical activity per week or fewer .The analyses were intention to treat; no randomized participants were excluded from analyses. Of the 106 participants randomized to active treatment, 97 (91.5%), 92 (86.7%) and 89 (83.9%) completed post-treatment, 6-month and 12-month assessments, respectively. Attrition was not statistically different between the two physical activity groups at any assessment time point. At the 12-month follow-up, 82.6% of low activity participants and 85.0% of high activity participants completed assessment .These findings suggest that CBT-I is similarly effective in older adults with lower baseline physical activity as among those with higher levels of baseline physical activity. In both the high and low physical activity groups, the expected trend of improved sleep outcomes in all sleep measures was observed, indicating improvement in sleep outcomes with CBT-I. For example, SOL-D decreased from baseline to all subsequent time points in both high and low physical activity groups, with no significant variation between the two groups. This information suggests that physicians should recommend CBT-I to older adults with insomnia disorder, even if their activity levels are low.Mixed-effects models found no statistical difference between the two physical activity groups for any of the sleep outcomes. However, this did not prove that the two physical activity groups were equivalent. Thus, we performed equivalence tests for the differences in changes in sleep outcomes from baseline to each time point for each sleep outcome to see if the two physical activity groups were indeed clinically equivalent. Equivalence tests are highly dependent on the threshold defining clinical significance, and we understand that different clinical significance thresholds could yield varying results. Thus, two thresholds were established. When a large threshold was used . Also, the limited sample size of the two physical activity groups could have impacted our ability to identify statistically significant differences. There were some differences in subjects included in this study, compared to the general US population of older adults. For example, this subject population had a greater percentage of active older adults compared to the national average  over the course of CBT-I treatment. Also, testing the effect of a more prominent physical activity component to CBT-I on the improvement of sleep outcomes in those with low baseline physical activity levels could prove to be beneficial.In conclusion, we found no clinically important differences in sleep outcomes from CBT-I among those with low vs. high levels of baseline physical activity. These findings suggest that CBT-I should be considered for the management of insomnia among older adults, regardless of their level of physical activity.TY, CA, JM, CF, LF, JD, YS and KJ contributed to the conception and design of the study. SJ organized the database. TY, MM and SJ performed the statistical analysis. TY wrote the first draft of the manuscript. CA wrote sections of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.