Lake Ontario Long Term Biological Monitoring Program: 1981, 1982 Data Base

The Bioindex, or Long Term Biological Monitoring Program, was developed to: 1) determine normal seasonal patterns and annual ranges of abundance, community structure, and when possible, productivity of the biological components - phytoplankton, zooplankton, and benthos; 2) relate the biological components to variations in the physical, nutrient, and biological environment; and, 3) assess the adopted sampling strategy for long term monitoring. The data bases from the first two years are summarized in this document

Lake Erie 1993, Western, West Central and Eastern Basins: Change in Trophic Status, and Assessment of the Abundance, Biomass and Production of the Lower Trophic Levels

The western and west central basins were mesotrophic and the eastern basin was oligotrophic, based on many biological and chemical parameters measured in 1993. Gradients were observed for most parameters, with chlorophyll a, nitrogen, phosphorus, silica, and light extinction decreasing from west to east. In the western basin, phytoplankton biomass declined by 51% from 1983-85. Phytoplankton photosynthesis (g C·m-2), predicted from total phosphorus (TP) using a relationship developed in other offshore productivity studies in Lake Ontario, declined by 35% in 1993, without a corresponding decline in phosphorus (P) loading or TP. Diatoms decreased and there was a shift towards smaller phytoplankton species. These changes were attributed to zebra mussel filtration, but were not of sufficient magnitude to reduce zooplankton biomass. In the west central basin, the reductions in phytoplankton biomass were modest. Photosynthesis (g C·m-2) in 1993, was in line with that predicted by TP and the empirical relationship developed in other offshore studies. Limited mussel populations in the west central basin, resulting from low hypolimnetic oxygen concentrations, caused little change in the phytoplankton. There also were no reductions in mean biomass of zooplankton from 1984-87. In the eastern basin, phytoplankton biomass declined by 49% from 1983-85. Photosynthesis (g C·m-2) declined by 50% from the value predicted, from TP and the empirical relationship developed for other studies, for 1983-85, without a decline in P-leading. TP was lower in 1993 and was attributed to filtering by Dreissena and subsequent redirection of pelagic material to the sediments. Phytoplankton species indicative of eutrophy were reduced and there was an overall shift towards smaller species. Zooplankton biomass was also reduced. Mean zooplankton community size and the loss of Daphnia sp. suggest that predation by planktivores as well as a reduced food supply, affected zooplankton biomass in 1993. The Dreissena population also affected the benthic community structure as Diporeia were virtually eliminated from the eastern basin and Gammarus increased in all basins. Benthic biomass was 40% higher on average than in 1979. Dreissena dominated benthic production at all stations except offshore in the west-central basin

Assessment of Abundance, Biomass and Production of the Lower Trophic Levels in the Eastern Basin of Lake Erie, 1994

The Lake Erie Biomonitoring (LEB) program conducted in 1994, focused on the eastern basin of the lake, resampling the same sites as in 1993. Nutrient conditions were similar in the two years. Responses differed between the stratified offshore and unstratified nearshore. At the offshore station, seasonal phytoplankton biomass was 56% higher in 1994 than in 1993 and apparently resulted from a reduction in grazing pressure by Dreissena. Dreissena biomass and their potential clearance rates at the offshore station were much lower in the spring of 1994 than in the spring of 1993 (2.5 vs. 14.9 m3·m·2·d·\u27), respectively. Despite this increase in phytoplankton biomass, chlorophyll (Chi) and phytoplankton photosynthesis (PP) were not significantly higher in 1994. Dinoflagellates, which have lower Chl:C and lower photosynthesis:Chl ratios than other groups of phytoplankton, accounted for much of the increase in biomass. Rotifer biomass decreased by 50% and zooplankton biomass by 40% between the two years. Calanoids were responsible for much of the decrease in zooplankton biomass. Composition also shifted towards larger bodied cladocerans, such as Daphnia and Bythotrephes, and away from Bosmina. This shift coincided with changes in predation pressure. Age-one smelt abundance was extremely high in 1993 and low in 1994, while the reverse was true of the YOY smelt. Age-one smelt consume mainly cladocerans and the YOY, copepods (REF). At the nearshore stations, seasonal PP and Chi were well below that expected given the total phosphorus (TP) concentration, indicating that Dreissena had an important impact on phytoplankton photosynthesis in this region. Low transparency due to suspended sediments also contributed to the low PP at station El. Zooplankton biomass was lower in 1994 than in 1993, and species composition and size shifted. Daphnia increased and calanoids and Bosmina decreased in the nearshore as in the offshore, presumably in response to changes in the smelt population. However, Bythotrephes decreased and rotifer biomass increased unlike in the offshore

Genomic and phenotypic analysis of BRCA2 mutated breast cancers reveals co-occurring changes linked to progression

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Inherited mutations in the BRCA2 gene greatly increase the risk of developing breast cancer. Consistent with an important role for BRCA2 in error-free DNA repair, complex genomic changes are frequently observed in tumors derived from BRCA2 mutation carriers. Here, we explore the impact of DNA copy-number changes in BRCA2 tumors with respect to phenotype and clinical staging of the disease. METHODS: Breast tumors (n = 33) derived from BRCA2 999del5 mutation carriers were examined in terms of copy-number changes with high-resolution aCGH (array comparative genomic hybridization) containing 385 thousand probes (about one for each 7 kbp) and expression of phenotypic markers on TMAs (tissue microarrays). The data were examined with respect to clinical parameters including TNM staging, histologic grade, S phase, and ploidy. RESULTS: Tumors from BRCA2 carriers of luminal and basal/triple-negative phenotypes (TNPs) differ with respect to patterns of DNA copy-number changes. The basal/TNP subtype was characterized by lack of pRb (RB1) coupled with high/intense expression of p16 (CDKN2A) gene products. We found increased proportions of Ki-67-positive cells to be significantly associated with loss of the wild-type (wt) BRCA2 allele in luminal types, whereas BRCA2wt loss was less frequent in BRCA2 tumors displaying basal/TNP phenotypes. Furthermore, we show that deletions at 13q13.1, involving the BRCA2wt allele, represents a part of a larger network of co-occurring genetic changes, including deletions at 6q22.32-q22.33, 11q14.2-q24.1, and gains at 17q24.1. Importantly, copy-number changes at these BRCA2-linked networking regions coincide with those associated with advanced progression, involving the capacity to metastasize to the nodes or more-distant sites at diagnosis. CONCLUSIONS: The results presented here demonstrate divergent paths of tumor evolution in BRCA2 carriers and that deletion of the wild-type BRCA2 allele, together with co-occurring changes at 6 q, 11 q, and 17 q, are important events in progression toward advanced disease.Eimskipafelag University Minningarsjodur Bergthoru Magnusdottur and Jakobs J Bjarnasonar Gongum Saman Icelandic Cancer Research Fund SKI Icelandic Centre for Research RANNIS The University of Icelan

Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS

Deaths Among Adult Patients with Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality.

Context:Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified.Objective:To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up.Design and Methods:All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed.Main Outcome Measures:Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up.Results:An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy.Conclusion:Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease

Treatment as Prevention for Hepatitis C (TraP Hep C) - a nationwide elimination programme in Iceland using direct-acting antiviral agents

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879.Merck Astellas Gilead Gilead Sciences AbbVie BM

Satellite detection, long-range transport, and air quality impacts of volcanic sulfur dioxide from the 2014–2015 flood lava eruption at Bárðarbunga (Iceland)

The 2014–2015 Bárðarbunga-Veiðivötn fissure eruption at Holuhraun produced about 1.5 km3 of lava, making it the largest eruption in Iceland in more than 200 years. Over the course of the eruption, daily volcanic sulfur dioxide (SO2) emissions exceeded daily SO2 emissions from all anthropogenic sources in Europe in 2010 by at least a factor of 3. We present surface air quality observations from across Northern Europe together with satellite remote sensing data and model simulations of volcanic SO2 for September 2014. We show that volcanic SO2 was transported in the lowermost troposphere over long distances and detected by air quality monitoring stations up to 2750 km away from the source. Using retrievals from the Ozone Monitoring Instrument (OMI) and the Infrared Atmospheric Sounding Interferometer (IASI), we calculate an average daily SO2 mass burden of 99 ± 49 kilotons (kt) of SO2 from OMI and 61 ± 18 kt of SO2 from IASI for September 2014. This volcanic burden is at least a factor of 2 greater than the average SO2 mass burden between 2007 and 2009 due to anthropogenic emissions from the whole of Europe. Combining the observational data with model simulations using the United Kingdom Met Office's Numerical Atmospheric-dispersion Modelling Environment model, we are able to constrain SO2 emission rates to up to 120 kilotons per day (kt/d) during early September 2014, followed by a decrease to 20–60 kt/d between 6 and 22 September 2014, followed by a renewed increase to 60–120 kt/d until the end of September 2014. Based on these fluxes, we estimate that the eruption emitted a total of 2.0 ± 0.6 Tg of SO2 during September 2014, in good agreement with ground-based remote sensing and petrological estimates. Although satellite-derived and model-simulated vertical column densities of SO2 agree well, the model simulations are biased low by up to a factor of 8 when compared to surface observations of volcanic SO2 on 6–7 September 2014 in Ireland. These biases are mainly due to relatively small horizontal and vertical positional errors in the simulations of the volcanic plume occurring over transport distances of thousands of kilometers. Although the volcanic air pollution episodes were transient and lava-dominated volcanic eruptions are sporadic events, the observations suggest that (i) during an eruption, volcanic SO2 measurements should be assimilated for near real-time air quality forecasting and (ii) existing air quality monitoring networks should be retained or extended to monitor SO2 and other volcanic pollutants

Improved Cortisol Exposure-Time Profile and Outcome in Patients with Adrenal Insufficiency: A Prospective Randomized Trial of a Novel Hydrocortisone Dual-Release Formulation.

Context:Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.Objective:The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.Design and Setting:We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.Patients:The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).Intervention:The same daily dose of hydrocortisone was administered as OD dual-release or TID.Main Outcome Measure:We evaluated cortisol pharmacokinetics.Results:Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).Conclusion:The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM

BRCA1 Promoter Methylation Status in 1031 Primary Breast Cancers Predicts Favorable Outcomes Following Chemotherapy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Breast Cancer 1 gene (BRCA1) is known to be inactivated in breast tumors by promoter methylation. Tumor cells in patients carrying a germline mutation in BRCA1 are sensitive to cytotoxic drugs that cause DNA double strand breaks. However, very little is known on whether patients with BRCA1 promoter methylated tumors are similarly sensitive to cytotoxic drugs. In this study, we address this by making use of extensive follow-up data on patients treated with cyclophosphamide, methotrexate, and fluorouracil in Iceland between 1976 and 2007. Methods: We analyzed BRCA1 promoter methylation by pyrosequencing DNA from tumor samples from 1031 patients with primary breast cancer. Of those, 965 were sporadic cases, 61 were BRCA2, and five were BRCA1 germline mutation carriers. All cases were examined with respect to clinicopathological parameters and breast cancer-specific survival in patients treated with cytotoxic drugs. Information on chemotherapy treatment in noncarriers was available for 26 BRCA1 methylated tumors and 857 unmethylated tumors. Results: BRCA1 was promoter methylated in 29 sporadic tumors or in 3.0% of cases (29 of 965), whereas none of the tumors derived from BRCA germline mutation carriers were promoter methylated. Important to note, patients with BRCA1 promoter methylation receiving chemotherapeutic drug treatment show highly improved breast cancer-specific survival compared with unmethylated controls (hazard ratio = 0.10, 95% confidence interval = 0.01 to 0.75, two-sided P = .02). Conclusions: BRCA1 promoter methylation is predictive of improved disease outcome in patients receiving cyclophosphamide, methotrexate, and fluorouracil drug treatment. Our results support the use of markers indicative of "BRCAness" in sporadic breast cancers to identify patients that are likely to benefit from the use of DNA-damaging agents.Icelandic Research Fund Gongum sama