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Introduction: We assessed the use of cerebrospinal fluid (CSF) biomarkers as an alternative to positron emission tomography (PET) for brain amyloid beta (Aβ) pathology confirmation in the EMERGE and ENGAGE clinical trials. Methods: EMERGE and ENGAGE were randomized, placebo‐controlled, Phase 3 trials of aducanumab in participants with early Alzheimer's disease. Concordance between CSF biomarkers (Aβ42, Aβ40, phosphorylated tau 181, and total tau) and amyloid PET status (visual read) at screening was examined. Results: Robust concordance between CSF biomarkers and amyloid PET visual status was observed (for Aβ42/Aβ40, AUC: 0.90; 95% CI: 0.83‐0.97; p < 0.0001), confirming CSF biomarkers as a reliable alternative to amyloid PET in these studies. Compared with single CSF biomarkers, CSF biomarker ratios showed better agreement with amyloid PET visual reads, demonstrating high diagnostic accuracy. Discussion: These analyses add to the growing body of evidence supporting CSF biomarkers as reliable alternatives to amyloid PET imaging for brain Aβ pathology confirmation. Highlights: CSF biomarkers and amyloid PET concordance were assessed in Ph3 aducanumab trials.Robust concordance between CSF biomarkers and amyloid PET was observed.CSF biomarker ratios increased diagnostic accuracy over single CSF biomarkers.CSF Aβ42/Aβ40 demonstrated high concordance with amyloid PET.Results support CSF biomarker testing as a reliable alternative to amyloid PET. [ABSTRACT FROM AUTHOR]

Research on collective decision-making is based on new decision-making theories and their methods are driven by group participation, human-computer interaction, and big data, to realize complex problem solving and intelligent decision-making in an open environment.However, the open environment is of high openness, complex interaction, and emerging behaviors, making collective decision-making face the challenges of difficult incentive mechanism design, uncontrollable decision-making individuals, diverse decision-making environments, and highly complex decosion-making information.Based on the era background of collective decision-making in an open environment, a new decision-making paradigm was proposed, its conceptual connotation, main challenges, and leading technologies for effective implementation of collective decision-making were sorted out.The successful cases of collective decision-making were analyzed, in order to support the application of new decision-making paradigms in the fields of economy, medical care, and people’s livelihood, and to promote progress and changes in the corresponding fields.

OBJECTIVE: To review the data informing the US Food and Drug Administration (FDA) approval for aducanumab for mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD). DATA SOURCES: At the time of writing there were no peer-reviewed published studies on aducanumab. All data presented are derived directly from the material Biogen submitted to the FDA for approval. The three studies that will be reviewed are: Multiple Dose Study of Aducanumab in Participants With Prodromal or Mild AD (PRIME), 221AD302 Phase 3 Study of Aducanumab in Early AD (EMERGE), 221AD301 Phase 3 Study of Aducanumab in Early AD (ENGAGE). DATA SYNTHESIS: PRIME, which was a phase 1 study, demonstrated the most common adverse drug reactions were amyloid-related imaging abnormalities (ARIA), which occurred at rates up to 47% (10 mg/kg group), headache (25%), urinary tract infection (16%), and upper respiratory tract infection (19%). EMERGE demonstrated that high-dose aducanumab was clinically significant at slowing down clinical decline. However, ENGAGE was terminated early based on a futility analysis. Prior to termination ENGAGE demonstrated no clinical difference between treatment and placebo regarding the primary endpoint of slowing clinical decline. CONCLUSION: Based on the data to date, it is difficult to accurately assess the role of aducanumab in patients with MCI or mild AD. EMERGE showed benefit with high-dose aducanumab slowing clinical decline. However, ENGAGE did not duplicate this benefit. With conflicting evidence of positive outcomes, future phase III studies are needed to confirm efficacy. [ABSTRACT FROM AUTHOR]

Background: Precise risk prediction of type 1 diabetes (T1D) facilitates early intervention and identification of risk factors prior to irreversible beta‐islet cell destruction, and can significantly improve T1D prevention and clinical care. Sharp et al. developed a genetic risk scoring (GRS) system for T1D (T1D‐GRS2) capable of predicting T1D risk in children of European ancestry. The T1D‐GRS2 was developed on the basis of causal genetic variants, thus may be applicable to minor populations, while a trans‐ethnic GRS for T1D may avoid the exacerbation of health disparities due to the lack of genomic information in minorities. Methods: Here, we describe a T1D‐GRS2 calculator validated in two independent cohorts, including African American children and European American children. Participants were recruited by the Center for Applied Genomics at the Children's Hospital of Philadelphia. Results: It demonstrates that GRS2 is applicable to the T1D risk prediction in the AA cohort, while population‐specific thresholds are needed for different populations. Conclusions: The study highlights the potential to further improve T1D‐GRS2 performance with the inclusion of additional genetic markers. [ABSTRACT FROM AUTHOR]

Objective: To facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by overcoming electronic health records (EHRs) batch effects.Material and Methods: We used 1872 billing codes in EHRs of 102 880 patients from 12 healthcare systems. Using tools borrowed from single-cell omics, we mitigated center-specific batch effects and performed clustering to identify patients with highly similar medical history patterns across the various centers. Our visualization method (PheSpec) depicts the phenotypic profile of clusters, applies a novel filtering of noninformative codes (Ranked Scope Pervasion), and indicates the most distinguishing features.Results: We observed 114 clinically meaningful profiles, for example, linking prostate hyperplasia with cancer and diabetes with cardiovascular problems and grouping pediatric developmental disorders. Our framework identified disease subsets, exemplified by 6 "other headache" clusters, where phenotypic profiles suggested different underlying mechanisms: migraine, convulsion, injury, eye problems, joint pain, and pituitary gland disorders. Phenotypic patterns replicated well, with high correlations of ≥0.75 to an average of 6 (2-8) of the 12 different cohorts, demonstrating the consistency with which our method discovers disease history profiles.Discussion: Costly clinical research ventures should be based on solid hypotheses. We repurpose methods from single-cell omics to build these hypotheses from observational EHR data, distilling useful information from complex data.Conclusion: We establish a generalizable pipeline for the identification and replication of clinically meaningful (sub)phenotypes from widely available high-dimensional billing codes. This approach overcomes datatype problems and produces comprehensive visualizations of validation-ready phenotypes. [ABSTRACT FROM AUTHOR]

Keywords: Codebook; coding; emerge; interpretation; methodology; positivist; reflexivity; theme; theory; topic summary EN Codebook coding emerge interpretation methodology positivist reflexivity theme theory topic summary 424 445 22 04/11/22 20220401 NES 220401 In 2006, psychologists Virginia Braun and Victoria Clarke published a paper entitled I Using thematic analysis in psychology i in I Qualitative Research in Psychology i . That type of analysis doesn't tell a thematic story. B Ginny: b One of the things that we articulated later (Braun and Clarke [11]; Braun, Clarke, and Rance [5]) is the idea of a central organising concept, the central idea of each theme. In the subsequent years they have written an award winning and best-selling qualitative research textbook I Successful Qualitative Research i (Braun and Clarke [11]), numerous chapters (e.g. Braun and Clarke [4]; Braun, Clarke, and Rance, [5]; Braun, Clarke, and Terry [6]; Braun, Clarke, and Weate, [7]; Clarke and Braun [21]), encyclopaedia entries (Clarke and Braun [18], [19]), commentaries (Braun and Clarke [13], [14]; Clarke and Braun [23]) and editorials (Braun and Clarke [12]; Clarke and Braun [22]), and created a website (https://www.psych.auckland.ac.nz/en/about/our-research/research-groups/thematic-analysis.html), about TA, as well as written chapters and papers (e.g. Braun, Clarke, and Gray [9]; Clarke and Braun [24]), and co-edited a book and a special issue related to other aspects of qualitative research (Braun et al. [15]; Braun, Clarke, and Gray [8]). That we can offer more on: Ginny and Victoria are currently finishing that very paper, and it will eventually be available in a forthcoming Special Issue of I Qualitative Research in Psychology i on quality in qualitative research (Clarke and Braun [25]). [Extracted from the article]

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Abstract Background The emergence of human infection with avian influenza A(H7N9) virus was reported in Wenshan City, southwestern China in 2017. The study describes the epidemiological and virological features of the outbreak and discusses the origin of the infection. Methods Poultry exposure and timelines of key events for each patient were collected. Samples derived from the patients, their close contacts, and environments were tested for influenza A(H7N9) virus by real-time reverse transcription polymerase chain reaction. Genetic sequencing and phylogenetic analysis were also conducted. Results Five patients were reported in the outbreak. An epidemiological investigation showed that all patients had been exposed at live poultry markets. The A(H7N9) isolates from these patients had low pathogenicity in avian species. Both epidemiological investigations of chicken sources and phylogenetic analysis of viral gene sequences indicated that the source of infection was from Guangxi Province, which lies 100 km to the east of Wenshan City. Conclusions In the study, a sudden emergence of human cases of H7N9 was documented in urban area of Wenshan City. Chickens were an important carrier in the H7N9 virus spreading from Guangxi to Wenshan. Hygienic management of live poultry markets and virological screening of chickens transported across regions should be reinforced to limit the spread of H7N9 virus.

Objective: The study sought to determine the dependence of the Electronic Medical Records and Genomics (eMERGE) rheumatoid arthritis (RA) algorithm on both RA and electronic health record (EHR) duration.Materials and Methods: Using a population-based cohort from the Mayo Clinic Biobank, we identified 497 patients with at least 1 RA diagnosis code. RA case status was manually determined using validated criteria for RA. RA duration was defined as time from first RA code to the index date of biobank enrollment. To simulate EHR duration, various years of EHR lookback were applied, starting at the index date and going backward. Model performance was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC).Results: The eMERGE algorithm performed well in this cohort, with overall sensitivity 53%, specificity 99%, positive predictive value 97%, negative predictive value 74%, and AUC 76%. Among patients with RA duration <2 years, sensitivity and AUC were only 9% and 54%, respectively, but increased to 71% and 85% among patients with RA duration >10 years. Longer EHR lookback also improved model performance up to a threshold of 10 years, in which sensitivity reached 52% and AUC 75%. However, optimal EHR lookback varied by RA duration; an EHR lookback of 3 years was best able to identify recently diagnosed RA cases.Conclusions: eMERGE algorithm performance improves with longer RA duration as well as EHR duration up to 10 years, though shorter EHR lookback can improve identification of recently diagnosed RA cases. [ABSTRACT FROM AUTHOR]

Background: The emergence of human infection with avian influenza A(H7N9) virus was reported in Wenshan City, southwestern China in 2017. The study describes the epidemiological and virological features of the outbreak and discusses the origin of the infection.Methods: Poultry exposure and timelines of key events for each patient were collected. Samples derived from the patients, their close contacts, and environments were tested for influenza A(H7N9) virus by real-time reverse transcription polymerase chain reaction. Genetic sequencing and phylogenetic analysis were also conducted.Results: Five patients were reported in the outbreak. An epidemiological investigation showed that all patients had been exposed at live poultry markets. The A(H7N9) isolates from these patients had low pathogenicity in avian species. Both epidemiological investigations of chicken sources and phylogenetic analysis of viral gene sequences indicated that the source of infection was from Guangxi Province, which lies 100 km to the east of Wenshan City.Conclusions: In the study, a sudden emergence of human cases of H7N9 was documented in urban area of Wenshan City. Chickens were an important carrier in the H7N9 virus spreading from Guangxi to Wenshan. Hygienic management of live poultry markets and virological screening of chickens transported across regions should be reinforced to limit the spread of H7N9 virus. [ABSTRACT FROM AUTHOR]

The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination. [ABSTRACT FROM AUTHOR]

Pepper veinal mottle virus (PVMV) is known to infect chilli pepper and belongs to the Chilli veinal mottle virus phylogroup of potyviruses. PVMV has recently appeared in Japan. In this study, we report six complete genomic sequences of PVMV isolates from chilli pepper (i.e. Capsicum annuum) in Okinawa Islands in Japan, and we determined the evolutionary relationships between Japanese isolates and the isolates reported earlier from African and Asian countries. Complete genomic sequences of the six Japanese PVMV isolates were 9760 nucleotides in length, excluding the nucleotide primer sequences used for amplifying 5ʹ end of the genomes. The major findings of this study are as follows: (1) all the Japanese isolates of PVMV have similar biological and molecular characteristics, indicating the presence of only one population in Japan; (2) there are at least three major phylogenetic groups of PVMV worldwide; (3) PVMV probably originated in East Africa; and (4) all the Asian isolates are closely related to the Ghanaian isolate. [ABSTRACT FROM AUTHOR]

• H7N9 virus spread into Chongqing most likely between late 2016 and early 2017 and resulted in human infections in months. • The most impacted premises and population in the epidemic were LPMs and poultry related workers respectively. • H7N9 virus has probably established in Chongqing posing a long-term threat to public health and local poultry industry. • Preventive measures should focus on rigorous management for LPMs and decreasing the exposure risk to poultry for humans. Influenza A(H7N9) virus has emerged and resulted in human infections in Chongqing, southwestern China since 2017. This study aimed to describe the epidemiological characteristics of the first epidemic in this region. The epidemiological data of patients were collected. Live poultry markets (LPMs), commercial poultry farms (CPFs) and backyard poultry farms (BPFs) were monitored, and poultry sources were registered. Samples derived from the patients, their close contacts, and the environments were tested for influenza A(H7N9) virus by real-time reverse transcriptase polymerase chain reaction. Genetic sequencing and phylogenetic analysis were also conducted. Since the confirmation of the first patient infected with influenza A(H7N9) virus on March 5, 2017, nine patients had been identified within four months in Chongqing. Their mean age was 45 years, 77.8% were male, 66.7% were urban residents and 55.6% were of poultry related occupation. All patients became infected after exposure to live chickens. The median time interval from initial detection of influenza A(H7N9) virus in Chongqing to the patients' onset was 75 days. Since initial detection in February 2017, influenza A(H7N9) virus was detected in 21 (53.8%) counties within four months. The proportion of positive samples was 2.94% (337/11,451) from February 2017 to May 2018, and was higher (χ2 = 75.78, P < 0.001) in LPMs (3.66%, 329/8979) than that in CPFs (0.41%, 5/1229) and BPFs (0.24%, 3/1243). The proportion of positive samples (34.4%, 22/64) at the premises to which the patients were exposed was significantly higher than that (5.7%, 257/4474) in premises with no patients. Phylogenetic analysis indicated that the viruses isolated in Chongqing belonged to the Yangtze River Delta lineage and resembled those circulated in Jiangsu and Anhui provinces between late 2016 and early 2017. Influenza A(H7N9) virus was newly introduced into Chongqing most likely between late 2016 and early 2017, which swept across half of Chongqing territory and resulted in human infections within months. The most impacted premises and population were LPMs and poultry related workers respectively in the epidemic. [ABSTRACT FROM AUTHOR]

The following is a critical reflection of the way in which today, in the world, the exercise of institutional (academic) research is conceived: the death of all serious thinking, the ability to judge castrated; in opposition to the task of the visceral researcher, from feeling, living, experiencing, from the other, with the other, for the other. Paradoxically, the first action is carried out, terribly, in opposition to any process of organic reflection, alive, meaning, between a living alterity and a formal commercial academicism, evidently commercial: to do research to score in the qualified records of every university. While the second action can surround the nothingness of the anonymity of serious people who conceive of research as a passionate exercise, of encounter with the other, the other and to make something emerge. Today, the university is a knowledge buying and selling company. All knowledge has become legitimated prostitution of knowledge. The methodology that has animated this paper is the deconstructive, action that will be carried out on the theming of the academic exercise of what is conceived as research. In this it will be concluded that the research is not a mere institutional academic exercise, and it is chosen to present it more as a relational exercise of co-construction with something. [ABSTRACT FROM AUTHOR]

Emerge application was used in Hampsson-Russell programs and that uses a combination of multiple 3D or 2D seismic attributes to predict some reservoir parameter of interest. In this research used the seismic inversion technique was performed on post-stack three dimensions (3D) seismic data in Nasriya oilfield with five wells and then used this results in Emerge analysis (training and application) were used to estimate reservoir properties (effective porosity) with multiattribute analysis derive relations between them at well locations. The horizon time slice of reservoir units of (Yb1, Yb3 and Yc) of Yamama Formation was made for property (effective porosity) to confirm match results and enhancement trends within these units. Because of the good prospects of the oil in the rocks of Cretaceous generally and Yamama Formation specially in the Nasriya oilfield and in view of the economic importance of Yamama Formation, which is considered as important formation that contains hydrocarbon accumulation, and one of the most important and oil production reservoirs in southern Iraq. [ABSTRACT FROM AUTHOR]

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be from a higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating a collection of relevant information from the health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and to make these publicly available to enhance dissemination and assist in making precision public health a reality. [ABSTRACT FROM AUTHOR]

The integration of electronic medical records (EMRs) and genomic research has become a major component of efforts to advance personalized and precision medicine. The Electronic Medical Records and Genomics (eMERGE) network, initiated in 2007, is an NIH-funded consortium devoted to genomic discovery and implementation research by leveraging biorepositories linked to EMRs. In its most recent phase, eMERGE III, the network is focused on facilitating implementation of genomic medicine by detecting and disclosing rare pathogenic variants in clinically relevant genes. Partners Personalized Medicine (PPM) is a center dedicated to translating personalized medicine into clinical practice within Partners HealthCare. One component of the PPM is the Partners Healthcare Biobank, a biorepository comprising broadly consented DNA samples linked to the Partners longitudinal EMR. In 2015, PPM joined the eMERGE Phase III network. Here we describe the elements of the eMERGE clinical center at PPM, including plans for genomic discovery using EMR phenotypes, evaluation of rare variant penetrance and pleiotropy, and a novel randomized trial of the impact of returning genetic results to patients and clinicians. [ABSTRACT FROM AUTHOR]

The social economy is a relative young field of research, but a very interesting and generous one. This paper brings into discussion this branch of the economy, at a time when social phenomenon is due to attention. As for prior works, here is short presentation of them, this approach trying to go further in this line. The main methods employed are the observation and survey. This research could be considered an essay on the proposed topic, hopping to be useful both for the academics and also for the state representatives that could take into account this subject. We hope that the reader is convinced of the paper's added value for this field of research. [ABSTRACT FROM AUTHOR]

The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA biobanks linked to electronic health records (EHRs) from multiple institutions. Approximately 52,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R2 (estimated correlation between the imputed and true genotypes), and the relationship between allelic R2 and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2) were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR.

Estimates from large scale genome sequencing studies indicate that each human carries up to 20 genetic variants that are predicted to results in loss of function (LOF) of protein-coding genes. While some are known disease–causing variants or common, tolerated, LOFs in nonessential genes, the majority remain of unknown consequence. We explore the possibility of using imputed GWAS data from large biorepositories such as the electronic medical record and genomics (eMERGE) consortium to determine the effects of rare LOFs. Here, we show that two hypocholesterolemia-associated LOF mutations in the PCSK9 gene can be accurately imputed into large-scale GWAS datasets which raises the possibility of assessing LOFs through genomics-linked medical records.

The goal of this paper is to review recent research on copy number variations (CNVs) and their association with complex and rare diseases. In the latter part of this paper, we focus on how large biorepositories such as the electronic medical record and genomics (eMERGE) consortium may be best leveraged to systematically mine for potentially pathogenic CNVs, and we end with a discussion of how such variants might be reported back for inclusion in electronic medical records as part of medical history.

The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA biobanks linked to electronic health records (EHRs) from multiple institutions. Approximately 51,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R² (estimated correlation between the imputed and true genotypes), and the relationship between allelic R² and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2) were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR. [ABSTRACT FROM AUTHOR]

Pegylated interferon-lambda-1a ( Lambda), a type III interferon ( IFN) in clinical development for the treatment of chronic HCV infection, has shown comparable efficacy and an improved safety profile to a regimen based on pegylated IFN alfa-2a (alfa). To establish a mechanistic context for this improved profile, we investigated the ex vivo effects of Lambda and alfa on cytokine and chemokine release, and on expression of IFN-stimulated genes ( ISGs) in primary human hepatocytes and peripheral blood mononuclear cells ( PBMCs) from healthy subjects. Our findings were further compared with changes observed in blood analysed from HCV-infected patients treated with Lambda or alfa in clinical studies. m RNA transcript and protein expression of the IFN- λ-limiting receptor subunit was lower compared with IFN- α receptor subunits in all cell types. Upon stimulation, alfa and Lambda induced ISG expression in hepatocytes and PBMCs, although in PBMCs Lambda-induced ISG expression was modest. Furthermore, alfa and Lambda induced release of cytokines and chemokines from hepatocytes and PBMCs, although differences in their kinetics of induction were observed. In HCV-infected patients, alfa treatment induced ISG expression in whole blood after single and repeat dosing. Lambda treatment induced modest ISG expression after single dosing and showed no induction after repeat dosing. Alfa and Lambda treatment increased IP-10, i TAC, IL-6, MCP-1 and MIP-1 β levels in serum, with alfa inducing higher levels of all mediators compared with Lambda. Overall, ex vivo and in vivo induction profiles reported in this analysis strongly correlate with clinical observations of fewer related adverse events for Lambda vs those typically associated with alfa. [ABSTRACT FROM AUTHOR]

1. The complex terrain and heterogeneous nature of the mountain environment coupled with remoteness from major centres of human activity makes mountains challenging locations for meteorological investigations. Mountainous areas tend to have more varied and more extreme weather than lowlands. 2. The EMERGE program has the primary aim of assessing the status of remote mountain and sub-arctic lakes throughout Europe for the first time. In this study, we describe the main features of the climate, ice-cover durations and recent temperature trends of these areas. The main weather characteristics of European mountain and sub-arctic lakes are their cold temperatures and year-round precipitation. Mean annual temperatures are generally close to 0 °C, and maximum summer temperatures reasonably close to 10 °C. 3. Maritime versus continental settings determine the main differences in annual-temperature range among lake districts (10.5 °C in Scotland to 26.7 °C in Northern Finland), and a similar factor for ice-cover duration. Radiation ranges from low (120 W m−2) in the high latitude sub-arctic and high (237 W m−2) in the southern ranges of the Pyrenees and Rila. Similarly, precipitation is high in the main Alpine chain (250 cm year−1 in the Central Southern Alps) and low in the continental sub-arctic (65 cm year−1 in Northern Finland). 4. The main temporal patterns in air temperature follow those of the adjacent lowlands. All the lake districts warmed during the last century. Spring temperature trends were highest in Finland; summer trends were weak everywhere; autumn trends were strongest in the west, in the Pyrenees and western Alps; while winter trends varied markedly, being high in the Pyrenees and Alps, low in Scotland and Norway and negative in Finland. 5. Two new, limnological case studies on Lake Redon, in the Pyrenees, highlight the sensitivity of remote lakes to projected changes in the global climate. These two case studies involve close linkages between extreme chemical-precipitation events and synoptic wind-patterns, and between thermocline behaviour and features of the large-scale circulation. 6. Individual lakes can be ultra-responsive to climate change. Even modest changes in future air temperatures will lead to major changes in lake temperatures and ice-cover duration and hence probably affect their ecological status. [ABSTRACT FROM AUTHOR]

High mountain lakes are sensitive to environ- mental change and the effects of air pollution and lake acidification have been recorded in many countries. The EU funded EMERGE programme included a pan-European assessment of the extent of acidification in mountain lakes located above the tree-line. A static critical loads model, the First-order Acidity Balance (FAB) model, was used to assess (1) the extent of critical load exceedance in 300 lakes in nine European lake districts and (2) the relative importance of sulphur and nitrogen deposition in contributing to acidification. The regional sensitivity of FAB to the choice of critical acid neutralising capacity (ANC: 0 or 20 μeq L-1) was explored. With a critical ANC value of 0 μeq L-1 only four lake districts had sites showing exceedance of critical loads; Piedmont Ticino, the Pyrenees, the Retezat Mountains and the Tatras. When a more stringent critical ANC of 20 μeq L-1 was used, all nine lake districts showed critical load exceedance in one or more lakes. For two lake districts, the Retezat Mountains of Romania and the Rila Mountains of Bulgaria, critical load exceedance is recorded here for the first time. Nitrogen is a more important agent of acidification in some areas such as the Pyrenees and Piedmont Ticino, and its relative importance is likely to increase elsewhere as pan-European measures to reduce sulphur deposition continue to take effect. Given the coarse scale deposition data used and potentially underestimated loads at high altitudes, the extent of the acidification problem may be under-represented here. [ABSTRACT FROM AUTHOR]

The integrated assessment models that drive atmospheric pollutant emission reduction policies within Europe, under the Convention on Long-range Trans-boundary Air Pollution, work at the scale of the EMEP grid (50 × 50 km). Critical loads are used to link anthropogenic deposition to adverse effects for individual ecosystems within each grid cell. The critical loads have two aspects, ecosystem area and the ecosystem specific critical load. The presence of highly acid-sensitive ecosystems within these grid cells can lead to very low critical loads of acidity which provide emission targets that are difficult to achieve: these cells are known as "binding grid squares". Since mountain lakes are highly sensitive to environmental change, their inclusion in critical loads assessments might be expected to result in lower EMEP scale critical loads. The combination of mountain lakes data with those from other ecosystems already included in the integrated modelling shows unexpected results. The average accumulated exceedance of critical loads of acidity may increase with either the presence of significant mountain lake catchment areas within grid cells or the presence of highly acidified clusters of sites. These circumstances occur in only a small number of grid cells. Furthermore, the relatively low sensitivity of mountain lakes to acidification in some regions means that their inclusion in EMEP scale models would lead to a relaxation of emission abatement requirements because of an increase in the area of ecosystems not exceeding critical loads and a decrease in AAE. Hence the potential effects of the inclusion of mountain lake critical loads of acidity in EMEP scale models vary greatly on a regional basis. The assumption that mountain lakes data could increase the incidence of "binding grid squares" is found to be unlikely. [ABSTRACT FROM AUTHOR]