What killed Frame Lake? A precautionary tale for urban planners

Frame Lake, located within the city of Yellowknife, Northwest Territories, Canada, has been identified as requiring significant remediation due to its steadily declining water quality and inability to support fish by the 1970s. Former gold mining operations and urbanization around the lake have been suspected as probable causes for the decline in water quality. While these land-use activities are well documented, little information is available regarding their impact on the lake itself. For this reason, Arcellinida, a group of shelled protozoans known to be reliable bioindicators of land-use change, were used to develop a hydroecological history of the lake. The purpose of this study was to use Arcellinida to: (1) document the contamination history of the lake, particularly related to arsenic (As) associated with aerial deposition from mine roaster stacks; (2) track the progress of water quality deterioration in Frame Lake related to mining, urbanization and other activities; and (3) identify any evidence of natural remediation within the lake. Arcellinida assemblages were assessed at 1-cm intervals through the upper 30 cm of a freeze core obtained from Frame Lake. The assemblages were statistically compared to geochemical and loss-on-ignition results from the core to document the contamination and degradation of conditions in the lake. The chronology of limnological changes recorded in the lake sediments were derived from 210Pb, 14C dating and known stratigraphic events. The progress of urbanization near the lake was tracked using aerial photography. Using Spearman correlations, the five most significant environmental variables impacting Arcellinida distribution were identified as minerogenics, organics, As, iron and mercury (p < 0.05; n = 30). Based on CONISS and ANOSIM analysis, three Arcellinida assemblages are identified. These include the Baseline Limnological Conditions Assemblage (BLCA), ranging from 17–30 cm and deposited in the early Holocene >7,000 years before present; the As Contamination Assemblage (ACA), ranging from 7–16 cm, deposited after ∼1962 when sedimentation began in the lake again following a long hiatus that spanned to the early Holocene; and the Eutrophication Assemblage (EA), ranging from 1–6 cm, comprised of sediments deposited after 1990 following the cessation of As and other metal contaminations. The EA developed in response to nutrient-rich waters entering the lake derived from the urbanization of the lake catchment and a reduction in lake circulation associated with the development at the lake outlet of a major road, later replaced by a causeway with rarely open sluiceways. The eutrophic condition currently charactering the lake—as evidenced by a population explosion of eutrophication indicator taxa Cucurbitella tricuspis—likely led to a massive increase in macrophyte growth and winter fish-kills. This ecological shift ultimately led to a system dominated by Hirudinea (leeches) and cessation of the lake as a recreational area

Diatom ecological response to deposition of the 833-850 CE White River Ash (east lobe) ashfall in a small subarctic Canadian lake

A <5 mm thick volcanic ashfall layer associated with the White River Ash (east lobe [WRAe]) originating from the eruption of Mount Churchill, Alaska (833-850 CE; 1,117–1,100 cal BP) was observed in two freeze cores obtained from Pocket Lake (62.5090°N, −114.3719°W), a small subarctic lake located within the city limits of Yellowknife, Northwest Territories, Canada. Here we analyze changes in diatom assemblages to assess impact of tephra deposition on the aquatic biota of a subarctic lake. In a well-dated core constrained by 8 radiocarbon dates, diatom counts were carried out at 1-mm intervals through an interval spanning  1 cm above and below the tephra layer with each 1 mm sub-sample represented about 2 years of deposition. Non-metric Multidimensional Scaling (NMDS) and Stratigraphically Constrained Incremental Sum of Squares (CONISS) analyses were carried out and three distinct diatom assemblages were identified throughout the interval. The lowermost “Pre-WRAe Assemblage (Pre-WRAeA)” was indicative of slightly acidic and eutrophic lacustrine conditions. Winter deposition of the tephra layer drove a subsequent diatom flora shift to the “WRAe Assemblage (WRAeA)” the following spring. The WRAeA contained elevated abundances of taxa associated with oligotrophic, nutrient depleted and slightly more alkaline lake waters. These changes were only apparent in samples within the WRAe containing interval indicating that they were short lived and only sustained for a single year of deposition. Immediately above the WRAe horizon, a third, “Post-WRAe Assemblage (Post-WRAeA)” was observed. This assemblage was initially similar to that of the Pre-WRAeA but gradually became more distinct upwards, likely due to climatic patterns independent of the WRAe event. These results suggest that lacustrine environments are sensitive to perturbations such as deposition of ash fall, but that ecological communities in subarctic systems can also have high resilience and can recover rapidly. If subsampling of the freeze cores was carried out at a more standard resolution (0.5–1 cm) these subtle diatom ecological responses to perturbation associated with the WRAe depositional event would not have been observed. This research illustrates the importance of high-resolution subsampling when studying the environmental impact of geologically “near instantaneous” events such as episodic deposition of ashfalls

Protocol: Conflict of interest issues when engaging stakeholders in health and healthcare guideline development: a systematic review

This is the protocol for a Campbell systematic review. The overall objective of this study is to gather and summarize the existing literature on conflict of interest issues when engaging stakeholders in guideline development

How could different obesity scenarios alter the burden of type 2 diabetes and liver disease in Saudi Arabia?

Introduction Obesity is a major risk factor for type 2 diabetes (T2DM) and liver disease, and obesity-attributable liver disease is a common indication for liver transplant. Obesity prevalence in Saudi Arabia (SA) has increased in recent decades. SA has committed to the WHO ‘halt obesity’ target to shift prevalence to 2010 levels by 2025. We estimated the future benefits of reducing obesity in SA on incidence and costs of T2DM and liver disease under two policy scenarios: 1) SA meets the ‘halt obesity’ target; 2) population body mass index (BMI) is reduced by 1% annually from 2020 to 2040. Methods We developed a dynamic microsimulation of working-age people (20-59 years) in SA between 2010 and 2040. Model inputs included population demographic, disease and healthcare cost data, and relative risks of diseases associated with obesity. In our two policy scenarios, we manipulated population BMI and compared predicted disease incidence and associated healthcare costs to a baseline ‘no change’ scenario. Results Adults 1.15 million combined cases of T2DM, liver disease and liver cancer could be avoided by 2040. Healthcare cost savings for the ‘halt obesity’ and 1% reduction scenarios are 46.7 and 32.8 billion USD, respectively. Discussion/Conclusion SA’s younger working-age population is set to meet the ‘halt obesity’ target, but those aged 35-59 are off-track. Even a modest annual 1% BMI reduction could result in substantial future health and economic benefits. Our findings strongly support universal initiatives to reduce population-level obesity, with targeted initiatives for working-age people ≥35 years of age

Diatom ecological response to deposition of the 833-850 CE White River Ash (east lobe) ashfall in a small subarctic Canadian lake

A <5 mm thick volcanic ashfall layer associated with the White River Ash (east lobe [WRAe]) originating from the eruption of Mount Churchill, Alaska (833-850 CE; 1,117-1,100 cal BP) was observed in two freeze cores obtained from Pocket Lake (62.5090◦N, −114.3719◦W), a small subarctic lake located within the city limits of Yellowknife, Northwest Territories, Canada. Here we analyze changes in diatom assemblages to assess impact of tephra deposition on the aquatic biota of a subarctic lake. In a well-dated core constrained by 8 radiocarbon dates, diatom counts were carried out at 1-mm intervals through an interval spanning 1 cm above and below the tephra layer with each 1 mm sub-sample represented about 2 years of dep

What killed Frame Lake? A precautionary tale for urban planners

Frame Lake, located within the city of Yellowknife, Northwest Territories, Canada, has been identified as requiring significant remediation due to its steadily declining water quality and inability to support fish by the 1970s. Former gold mining operations and urbanization around the lake have been suspected as probable causes for the decline in water quality. While these land-use activities are well documented, li

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

De novo variants of CSNK2B cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway

CSNK2B encodes for casein kinase II subunit beta (CK2b), the regulatory subunit of casein kinase II (CK2), which is known to mediate diverse cellular pathways. Variants in this gene have been recently identified as a cause of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), but functional evidence is sparse. Here, we report five unrelated individuals: two of them manifesting POBINDS, while three are identified to segregate a new intellectual disability-craniodigital syndrome (IDCS), distinct from POBINDS. The three IDCS individuals carried two different de novo missense variants affecting the same codon of CSNK2B. Both variants, NP_001311.3; p.Asp32His and NP_001311.3; p.Asp32Asn, lead to an upregulation of CSNK2B expression at transcript and protein level, along with global dysregulation of canonical Wnt signaling. We found impaired interaction of the two key players DVL3 and b-catenin with mutated CK2b. The variants compromise the kinase activity of CK2 as evident by a marked reduction of phosphorylated b-catenin and consequent absence of active b-catenin inside nuclei of the patient-derived lymphoblastoid cell lines (LCLs). In line with these findings, whole-transcriptome profiling of patient-derived LCLs harboring the NP_001311.3; p.Asp32His variant confirmed a marked difference in expression of genes involved in the Wnt signaling pathway. In addition, whole-phosphoproteome analysis of the LCLs of the same subject showed absence of phosphorylation for 313 putative CK2 substrates, enriched in the regulation of nuclear b-catenin and transcription of the target genes. Our findings suggest that discrete variants in CSNK2B cause dominant-negative perturbation of the canonical Wnt signaling pathway, leading to a new craniodigital syndrome distinguishable from POBINDS

Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other ("linked") epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10(+) T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti -IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans