Biogeosciences Perspectives on Integrated, Coordinated, Open, Networked (ICON) Science.

This article is composed of three independent commentaries about the state of Integrated, Coordinated, Open, Networked (ICON) principles in the American Geophysical Union Biogeosciences section, and discussion on the opportunities and challenges of adopting them. Each commentary focuses on a different topic: (a) Global collaboration, technology transfer, and application (Section 2), (b) Community engagement, community science, education, and stakeholder involvement (Section 3), and (c) Field, experimental, remote sensing, and real-time data research and application (Section 4). We discuss needs and strategies for implementing ICON and outline short- and long-term goals. The inclusion of global data and international community engagement are key to tackling grand challenges in biogeosciences. Although recent technological advances and growing open-access information across the world have enabled global collaborations to some extent, several barriers, ranging from technical to organizational to cultural, have remained in advancing interoperability and tangible scientific progress in biogeosciences. Overcoming these hurdles is necessary to address pressing large-scale research questions and applications in the biogeosciences, where ICON principles are essential. Here, we list several opportunities for ICON, including coordinated experimentation and field observations across global sites, that are ripe for implementation in biogeosciences as a means to scientific advancements and social progress.

Land Use, Not Stream Order, Controls N2O Concentration and Flux in the Upper Mara River Basin, Kenya.

Anthropogenic activities have led to increases in nitrous oxide (N2O) emissions from river systems, but there are large uncertainties in estimates due to lack of data in tropical rivers and rapid increase in human activity. We assessed the effects of land use and river size on N2O flux and concentration in 46 stream sites in the Mara River, Kenya, during the transition from the wet (short rains) to dry season, November 2017 to January 2018. Flux estimates were similar to other studies in tropical and temperate systems, but in contrast to other studies, land use was more related to N2O concentration and flux than stream size. Agricultural stream sites had the highest fluxes (26.38 ± 5.37 N2O-N µg·m-2·hr-1) compared to both forest and livestock sites (5.66 ± 1.38 N2O-N µg·m-2·hr-1 and 6.95 ± 2.96 N2O-N µg·m-2·hr-1, respectively). N2O concentrations in forest and agriculture streams were positively correlated to stream carbon dioxide (CO2-C(aq)) but showed a negative correlation with dissolved organic carbon, and the dissolved organic carbon:dissolved inorganic nitrogen ratio. N2O concentration in the livestock sites had a negative relationship with CO2-C(aq) and a higher number of negative fluxes. We concluded that in-stream chemoautotrophic nitrification was likely the main biogeochemical process driving N2O production in agricultural and forest streams, whereas complete denitrification led to the consumption of N2O in the livestock stream sites. These results point to the need to better understand the relative importance of nitrification and denitrification in different habitats in producing N2O and for process-based studies.

[Evaluation of antiretroviral treatment in a cohort of 1,620 HIV-infected patients in Togo]. / Évaluation du traitement antirétroviral de 1 620 personnes infectées par le VIH au Togo.

PURPOSE: The purpose of this study was to evaluate the efficacy of antiretroviral treatment for HIV-infected patients in Togo. PATIENTS AND METHOD: This retrospective study covered the period from January 2001 to January 2009 and included all HIV-infected patients who received antiretroviral therapy for at least 12 months. RESULTS: The study included 1,620 of the 8,901 patients (18.2%) treated with antiretroviral therapy. Mean patient age was 34.8 ± 11.4 years and the male/female sex-ratio was 0.4. When treatment began, the mean CD4+ T lymphocyte count was 143/mm(3) and mean patient weight was 53.3 kg. Overall, 263 of the 1,620 subjects (16.2%) had opportunistic infections before starting antiretroviral treatment. The most frequently used antiretroviral combination was stavudine/lamivudine/nevirapine (91.7%). The compliance rate for the first 12 months was 89.6%, and the antiretroviral regimen was changed in 5.9% of cases. After 36 months, mean weight gain was 8.8 kg and the mean increase in the CD4(+) T lymphocyte count was 265 cells/mm(3). The number of opportunistic infections decreased from 263 cases at the beginning of antiretroviral treatment to 9 after three years of treatment. During follow-up, 258 deaths were recorded, for a cumulative case fatality rate of 15.9%. The most common side effects were cutaneous toxicity and anemia in the short term and neurological toxicity, lipodystrophy and hepatotoxicity over the long term. DISCUSSION: This study confirms the efficacy of antiretroviral treatment of HIV-infected patients in Togo. These findings should encourage policy-makers to work toward universal access to antiretroviral treatment for people living with HIV.

[Biological profile of adult patients infected with HIV at initiation of antiretroviral therapy in Togo]. / Profil biologique des patients adultes infectés par le VIH à l'initiation du traitement antirétroviral au Togo.

OBJECTIVE: The study's objective was to determine the CD4 count and laboratory abnormalities in adults infected with HIV at initiation of antiretroviral therapy (ART) in Togo. METHODS: A retrospective and descriptive study was made of all patients on HAART in 2009 in Togo. RESULTS: A total of 5106 patients were included with a median age of 35 years. 68.6% were female patients. HIV1 infection was predominant (97.5%). The mean CD4) count at treatment initiation was 134 cells/µl. Among these patients, 22.1% had a CD4 count below 50 cells/µl and 73.8% had a CD4 count below 200 cells/µl. The median hemoglobin level was 10.4 g/dl. Transaminase level was elevated (grade 1 and above) in 55.9% of patients for AST, and in 29.8% of patients for ALT. Mean serum creatinine was 9.6 ± 5 mg/l. CONCLUSION: Initiation of ART is late in Togo, consequently a significant proportion of patients present with severe immunosuppression on initiation of treatment. Improving strategies for mass screening should increase the number of patients treated early to better meet WHO 2009 recommendations.

[Leprosy in Lome, Togo: retrospective study of 383 cases]. / Lèpre à Lomé (Togo): étude rétrospective de 383 cas.

The goal of this study was to determine the therapeutic outcomes and clinical forms of leprosy diagnosed in Lomé, Togo. This retrospective study was carried out in leprosy patients managed at the National Center of Dermatology in Lomé between January 1990 and December 2005. During the study period, 383 cases of leprosy were recorded including 366 new cases. The annual diagnosis rate was 23 cases per year. Mean patient age was 35.6 +/- 15.4 years. The proportion of patients in the 15 to 49-year-old bracket and in the under-15-year-old bracket was 75% and 6,4% respectively. Male-to-female ratio was 1.36. Prevalence dropped from 4.4/100,000 inhabitants in 1990 to 1.9/100,000 inhabitants in 2005. The detection rate decreased from 6.8/100,000 inhabitants in 1990 to 2.1/100,000 inhabitants in 2005. There was a high prevalence of multibacillary cases after 1995. The incidence of the leprous reactions was 11%. The infirmity rate was 8.5%. The cure rate was 78% after multidrug therapy in 98.2% of cases. Relapse occurred in 6.1% of cases and 16% were lost from follow-up. This study confirms the decreasing prevalence of leprosy in Lomé as well as its changing clinical profile with an increase in multibacillary leprosy.

[Emergence of multidrug resistant Salmonella strains in Lome (Togo)]. / Emergence des souches de salmonelles multirésistantes aux antibiotiques à Lomé (Togo).

OBJECTIVE: This study had for aim to compare antibiotic resistance of 332 Salmonella enterica strains identified in human samples in the course of infections, in Lome. DESIGN: The strains were collected over two periods: 1998-2002 (N=168) and 2003-2004 (N=164). The antibiotic susceptibility test was performed by disk diffusion assay. RESULTS: The main serotypes identified were 147 Salmonella Typhi (44.3%), 97 Salmonella Typhimurium (29.2%), and 74 Salmonella Enteritidis (22.3%). The proportions of strains resistant to chloramphenicol, cotrimoxazol, and amoxicillin (first line antibiotics) varied respectively from 33, 46, and 57% in 1998-2002 to 73, 79, and 82% in 2003-2004 (P<0.0001). The percentage of resistance to ciprofloxacin or ceftriaxone was inferior to 10%. CONCLUSION: Fluoroquinolones and third generation cephalosporins have become the first line antibiotics for the treatment of Salmonella in Lome (Togo).

Finnish case-control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis.

Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes the R620W amino-acid change as a putative susceptibility factor in autoimmune diseases. The current study was undertaken to examine a large cohort of Finnish rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) subjects using both population control and, importantly, family-based association methods. The latter is particularly important when, as is the case for the 1858 C/T polymorphism, the frequency of the variant allele (T) differs in both major ancestral populations and in subpopulations. The analysis of rheumatoid factor-positive 1030 RA probands from Finland provides strong support for association of this variant in both population studies (allele specific odds ratio (OR)=1.47, 95% confidence interval (CI)=1.27-1.70, P=3 x 10(-7)) and in family studies (P<10(-6)). In contrast, no allelic association was seen with JIA (230 probands) and only weak evidence for a genotypic effect of 1858T homozygotes was observed in this population.

HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC.

This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci ( approximately 200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1(*)030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1(*)030101 and DRB1(*)08 and (*)11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1(*)08 and (*)11 (P<0.000003) and DPB1(*)030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects.

OBJECTIVES: Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure. METHODS: A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978 and 1980. Detailed histories of smoking and RF (sensitized sheep cell agglutination test) were obtained in the basic examination. In 2000, serum cotinine and thiocyanate were determined from serum samples collected at baseline and stored at -20 degrees C. A cut-off point of 100 microg/l was used for serum cotinine and 10 micromol/l for thiocyanate to indicate active smoking. RESULTS: There was a close association between smoking and strongly positive RF. After adjustment for age, sex, coffee consumption and region, the odds ratios (95% confidence intervals in brackets) in current smokers and in those who had quit smoking were 3.94 (2.04-7.61) and 2.71 (1.33-5.53), respectively, compared with those who had never smoked. Among current smokers, the intensity, duration or tertiles of pack-years of smoking were not related to RF. No relationship between serum cotinine or thiocyanate and RF positivity was observed within the subgroups of current smokers and those who had quit. Among those who reported that they had never smoked but who nevertheless had serum cotinine levels at least 100 microg/l, the adjusted odds ratio of strongly positive RF was 4.48 (1.48-13.50) compared with people who had never smoked and whose serum cotinine levels were less than 100 microg/l. CONCLUSIONS: The results are not in line with the hypothesis of a dose-response relationship between smoking exposure and RF positivity.

Joint symptoms and diseases associated with moisture damage in a health center.

Rheumatic diseases do not usually cluster in time and space. It has been proposed that environmental exposures may initiate autoimmune responses. We describe a cluster of rheumatic diseases among a group of health center employees who began to complain of symptoms typically related to moldy houses, including mucocutaneous symptoms, nausea and fatigue, within a year of moving into a new building. Dampness was found in the insulation space of the concrete floor below ground level. Microbes indicating mold damage and actinobacteria were found in the flooring material and in the outer wall insulation. The case histories of the personnel involved were examined. All 34 subjects working at the health center had at least some rheumatic complaints. Two fell ill with a typical rheumatoid factor (RF)-positive rheumatoid arthritis (RA), and 10 had arthritis that did not conform to any definite arthritic syndrome (three met the classification criteria for RA). Prior to moving into the problem building one subject had suffered reactive arthritis, which had then recurred. Another employee had undiagnosed ankylosing spondylitis and later developed psoriatic arthritis, and another developed undifferentiated vasculitis. A total of 16 subjects developed joint pains, 11 of these after beginning work at the health center. Three subjects developed Raynaud's symptom. Fourteen cases had elevated levels of circulating immune complexes in 1998, 17 in 1999, but there were only three cases in 2001, when the health center had been closed for 18 months. The high incidence of joint problems among these employees suggests a common triggering factor for most of the cases. As some of the symptoms had tended to subside while the health center was closed, the underlying causes are probably related to the building itself and possibly to the abnormal microbial growth in its structures.

Severe childhood uveitis without overt arthritis.

OBJECTIVE: To look for forme fruste (incomplete) forms of juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: The study involved 6 patients (3 girls and 3 boys) without overt arthritis who had been sent for ophthalmologic and rheumatologic evaluation because of uveitis resembling that seen in JIA. RESULTS: Two patients evinced no evidence of arthritis, 3 had non-specific signs and symptoms such as pains or valgus ankle and one may have had an episode of arthritis. Five patients carried the HLA allele B27 and 4 were positive for antinuclear antibodies. The mean age at diagnosis of uveitis was 8.4 years (range 3.5-14.2 years) and the mean follow-up period was 6.2 years (range 3.8-7.3 years). All patients had obviously had their uveitis for a long period prior to the first contact with an ophthalmologist. In 3 patients uveitis was asymptomatic when diagnosed, 2 had mild conjunctival injection and one had exacerbation of the disease process. Subsequently the uveitis was asymptomatic and bilateral in all patients. Complications of uveitis were common: cataract was found in 4 patients, glaucoma in 1 patient, cystoid macular edema in 4, posterior synechiae in 5 and band keratopathy in 3. The final visual acuity was poor in one eye of 1 patient despite effective treatment of uveitis. Uveitis was still active in all patients at the close of follow-up. CONCLUSION: Asymptomatic uveitis, which is frequently positive for antinuclear antibodies, can occur in children who show no clear evidence of arthritis. Complications occur in consequence of a delay in the diagnosis of insidious uveitis.

Analysis of MHC region genetics in Finnish patients with juvenile idiopathic arthritis: evidence for different locus-specific effects in polyarticular vs pauciarticular subsets and a shared DRB1 epitope.

This study used Finnish juvenile idiopathic arthritis (JIA) probands with pauciarticular and rheumatoid factor (RF) negative polyarticular subtypes of JIA to further define the genetic susceptibility to JIA. We examined 16 markers spanning an 18 cM region of chromosome 6 encompassing the MHC and surrounding genomic region in a set of 235 Finnish JIA nuclear families and 639 Finnish control individuals. Analysis by case/control association and transmission disequilibrium test (TDT) methods each demonstrated strong evidence for a susceptibility locus near the D6S2447 microsatellite (P<10(-6) for both methods) that is flanked by DQB1 and DRB1. Analysis of the DRB1 locus suggested that DRB1*0801 and DRB1*1101 rather than DQA1 or other HLA alleles may be responsible for conferring susceptibility to disease. These findings are consistent with the most compelling results of previous reports on HLA associations and suggest a JIA DRB1 shared epitope encompassing critical amino-acid residues in the third hypervariable region of this molecule. Most importantly, in pauciarticular patients, the strong association does not extend to proximal markers as it does in polyarticular patients (P<0.00001). Analysis strongly suggests that the difference is because of additional JIA susceptibility loci within the MHC being present in polyarticular RF negative patients.

Occurrence of chronic inflammatory rheumatic diseases among parents of multiple offspring affected by juvenile idiopathic arthritis.

OBJECTIVE: The rarity of reports on extended multiplex families points out that the genetic component in juvenile idiopathic arthritis (JIA) might not be particularly strong. Our objective was to determine the frequency of chronic inflammatory rheumatic diseases among the parents who had two or more offspring affected by JIA. METHODS: During the last 17 years patients with JIA treated at the Rheumatism Foundation Hospital in Heinola and their parents have been systematically asked about the familial occurrence of rheumatic diseases. A total of 45 families with more than one sibling affected by JIA were found among about 2,300 JIA cases. In these "multicase families", 9 parents from 8 families also had a diagnosis of chronic inflammatory rheumatic disease. Their case histories were studied. RESULTS: Four of the parents had had JIA (one subsequently developed ankylosing spondylitis), and 4 had rheumatoid factor-negative chronic arthritis (one had also had chronic iritis since the age of 10, resembling that seen in JIA). Three of them had features of JIA and only one met the classification criteria for rheumatoid arthritis. One had ankylosing spondylitis. CONCLUSIONS: Since the expected number of JIA cases among the 90 parents was about 0.2, there was drastic increase in JIA frequency among the parents in families with multiple offspring also affected by JIA. These results suggest that JIA susceptibility genes may likely be clustered in these families.

Increased type I collagen degradation correlates with disease activity in reactive arthritis.

OBJECTIVE: The assay for the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) has been shown to reflect increased type I collagen degradation in patients with rheumatoid arthritis. To look for increased collagen degradation in other inflammatory rheumatic diseases, we studied plasma ICTP in patients with reactive arthritis (ReA). METHODS: ICTP was determined by radioimmunoassay from 69 ReA patients. ICTP data on 56 patients aged > or = 20 years were compared with normal ICTP values available for that age group. RESULTS: The median (range) plasma ICTP concentration of the patients > or = 20 years of age was 3.9 (2.1-9.6) micrograms/l, and in 13 (23%) of them the value was elevated if compared with the normal upper reference limit (mean + 2SD), 5.2 micrograms/l, given by the manufacturer. The mean (SD) duration of joint symptoms was 76 (61) days in patients with ReA. Modest albeit statistically significant correlations were noted between the plasma ICTP and the erythrocyte sedimentation rate, C-reactive protein and the Lansbury articular index (Spearman's r 0.39, 0.37 and 0.29, respectively). The median values for all of the above mentioned parametres were at least twice as high in the group of patients with elevated ICTP compared with those in patients with normal values (p < 0.05). No statistically significant correlation was detected between the plasma ICTP and the duration of joint symptoms. CONCLUSION: Increased type I collagen degradation can take place in ReA, and this process seems to correlate with the extent and activity of the joint disease.

Regional differences in Finland in the prevalence of rheumatoid factor in the presence and absence of arthritis.

OBJECTIVES: To look for possible regional differences in the prevalence of rheumatoid factor (RF) in the presence and absence of arthritis. METHODS: The study covered a representative sample of the Finnish population aged 30 years or over, primarily comprising 8000 people, of whom 7217 participated in the field survey carried out in 1978-80. RF from serum samples from 7116 subjects was determined by the Waaler-Rose (sensitised sheep cell agglutination) test. Titres >or=32 were regarded as positive and titres >or=128 as strongly positive. Arthritis was diagnosed by a thorough clinical examination. RESULTS: In the absence of arthritis the prevalence of positive and strongly positive RF reactions was 2.1% and 1.0%, respectively. The lowest prevalence of strongly "false positive" RF occurred in south western Finland. After adjustment for age, sex, smoking, and coffee consumption the odds ratio of having a strongly "false positive" RF reaction in eastern Finland was 3.16 (95% confidence interval 1.29 to 7.72) and in northern Finland 2.94 (1.13 to 7.64) compared with south western Finland. The corresponding odds ratio of strongly RF positive arthritis in eastern Finland was 5.08 (1.41 to 18.27). CONCLUSION: Regional differences are found in the prevalence of a strongly positive RF reaction in the Finnish population. The findings are in accordance with recent results from another study concerning regional differences in the incidence of rheumatoid arthritis in Finland.

Filaggrin related antibodies among the aged.

BACKGROUND: The mean age at onset of new cases of rheumatoid arthritis (RA) has increased markedly. Because the prevalence of false positive rheumatoid factor reactions increases with advancing age, the diagnostic value of this test has limitations among the aged. OBJECTIVE: To study the occurrence of two filaggrin related antibodies in an aged population. METHODS: The study covered 300 subjects aged 78-88 years, one of whom had RA. The sera were tested with enzyme linked immunosorbent assays (ELISAs), using filaggrin purified from human skin and citrullinated cyclic peptide (CCP) as antigens. RESULTS: One patient with RA was positive for both antibodies. When the cut off level for positive reactions was set at the 98th centile of healthy blood donors, 24 (8%) of the other subjects were positive for antibodies against filaggrin, but only one against CCP. CONCLUSION: The test for anti-CCP antibody has better specificity than the test for antibodies against filaggrin among the aged.