Response of CO₂ and CH₄ emissions from Arctic tundra soils to a multifactorial manipulation of water table, temperature and thaw depth

Significant uncertainties persist concerning how Arctic soil tundra carbon emission responds to environmental changes. In this study, 24 cores were sampled from drier (high centre polygons and rims) and wetter (low centre polygons and troughs) permafrost tundra ecosystems. We examined how soil CO2 and CH4 fluxes responded to laboratory-based manipulations of soil temperature (and associated thaw depth) and water table depth, representing current and projected conditions in the Arctic. Similar soil CO2 respiration rates occurred in both the drier and the wetter sites, suggesting that a significant proportion of soil CO2 emission occurs via anaerobic respiration under water-saturated conditions in these Arctic tundra ecosystems. In the absence of vegetation, soil CO2 respiration rates decreased sharply within the first 7 weeks of the experiment, while CH4 emissions remained stable for the entire 26 weeks of the experiment. These patterns suggest that soil CO2 emission is more related to plant input than CH4 production and emission. The stable and substantial CH4 emission observed over the entire course of the experiment suggests that temperature limitations, rather than labile carbon limitations, play a predominant role in CH4 production in deeper soil layers. This is likely due to the presence of a substantial source of labile carbon in these carbon-rich soils. The small soil temperature difference (a median difference of 1 ◦C) and a more substantial thaw depth difference (a median difference of 6 cm) between the high and low temperature treatments resulted in a non-significant difference between soil CO2 and CH4 emissions. Although hydrology continued to be the primary factor influencing CH4 emissions, these emissions remained low in the drier ecosystem, even with a water table at the surface. This result suggests the potential absence of a methanogenic microbial community in high-centre polygon and rim ecosystems. Overall, our results suggest that the temperature increases reported for these Arctic regions are not responsible for increases in carbon losses. Instead, it is the changes in hydrology that exert significant control over soil CO2 and CH4 emissions

FULFIL Trial: Once-Daily Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease

RATIONALE: Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited. OBJECTIVES: We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy. METHODS: FULFIL was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA(®) inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler(®)). A patient subgroup remained on blinded treatment for up to 52 weeks. Co-primary endpoints were change from baseline in trough forced expiratory volume in 1 second (FEV1) and in St George's Respiratory Questionnaire (SGRQ) Total score, at Week 24. MEASUREMENTS AND MAIN RESULTS: In the intent-to-treat population (N = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899): mean change from baseline in FEV1 was 142 mL (95% confidence interval [CI], 126,158) and -29 mL (95% CI, -46,-13), respectively; mean change from baseline SGRQ was -6.6 units (95% CI, -7.4,-5.7) and -4.3 units (95% CI, -5.2,-3.4), respectively. For both endpoints, the between-group differences were statistically significant (P < 0.001). There was a statistically significant reduction in moderate/severe exacerbation rate with triple versus ICS/LABA therapy (35% reduction, 95% CI, 14,51; P = 0.002). The safety profile of triple therapy reflected the known profiles of the components. CONCLUSIONS: These results support the benefits of single inhaler triple therapy compared with ICS/LABA therapy, in patients with advanced COPD. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02345161

Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in COPD Patients

Rationale: The IMPACT trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with COPD at risk of future exacerbations. 574 patients were censored from the original analysis due to incomplete vital status information. Objective: Report ACM and impact of stepping down therapy, following collection of additional vital status data. Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25µg, FF/VI 100/25µg or UMEC/VI 62.5/25µg following a run-in on their COPD therapies. Time to ACM was prespecified. Additional vital status data collection and subsequent analyses were performed post hoc. Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n=10,355), documenting 98(2.36%) deaths on FF/UMEC/VI, 109(2.64%) on FF/VI, and 66(3.19%) on UMEC/VI. For FF/UMEC/VI, the hazard ratio for death was 0.72 (95%CI: 0.53,0.99;P=0.042) versus UMEC/VI and 0.89 (95%CI: 0.67,1.16;P=0.387) versus FF/VI. Independent adjudication confirmed lower rates of cardiovascular and respiratory death, and death associated with the patient’s COPD. Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations. Funding: GSK(CTT116855/NCT02164513)

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Factors Associated with HIV/AIDS Diagnostic Disclosure to HIV Infected Children Receiving HAART: A Multi-Center Study in Addis Ababa, Ethiopia

BACKGROUND: Diagnostic disclosure of HIV/AIDS to a child is becoming an increasingly common issue in clinical practice. Nevertheless, some parents and health care professionals are reluctant to inform children about their HIV infection status. The objective of this study was to identify the proportion of children who have knowledge of their serostatus and factors associated with disclosure in HIV-infected children receiving HAART in Addis Ababa, Ethiopia. METHODS: A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18, 2008-April 28, 2008. The study populations were parents/caretakers and children living with HIV/AIDS who were receiving Highly Active Antiretroviral Therapy (HAART) in selected hospitals in Addis Ababa. Univariate and multivariate logistic regression analysis were carried out using SPSS 12.0.1 statistical software. RESULTS: A total of 390 children/caretaker pairs were included in the study. Two hundred forty three children (62.3%) were between 6-9 years of age. HIV/AIDS status was known by 68 (17.4%) children, 93 (29%) caretakers reported knowing the child's serostatus two years prior to our survey, 180 (46.2%) respondents said that the child should be told about his/her HIV/AIDS status when he/she is older than 14 years of age. Children less than 9 years of age and those living with educated caregivers are less likely to know their results than their counterparts. Children referred from hospital's in-patient ward before attending the HIV clinic and private clinic were more likely to know their results than those from community clinic. CONCLUSION: The proportion of disclosure of HIV/AIDS diagnosis to HIV-infected children is low. Strengthening referral linkage and health education tailored to educated caregivers are recommended to increase the rate of disclosure

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

A Novel Role for the Centrosomal Protein, Pericentrin, in Regulation of Insulin Secretory Vesicle Docking in Mouse Pancreatic β-cells

The centrosome is important for microtubule organization and cell cycle progression in animal cells. Recently, mutations in the centrosomal protein, pericentrin, have been linked to human microcephalic osteodysplastic primordial dwarfism (MOPD II), a rare genetic disease characterized by severe growth retardation and early onset of type 2 diabetes among other clinical manifestations. While the link between centrosomal and cell cycle defects may account for growth deficiencies, the mechanism linking pericentrin mutations with dysregulated glucose homeostasis and pre-pubertal onset of diabetes is unknown. In this report we observed abundant expression of pericentrin in quiescent pancreatic β-cells of normal animals which led us to hypothesize that pericentrin may have a critical function in β-cells distinct from its known role in regulating cell cycle progression. In addition to the typical centrosome localization, pericentrin was also enriched with secretory vesicles in the cytoplasm. Pericentrin overexpression in β-cells resulted in aggregation of insulin-containing secretory vesicles with cytoplasmic, but not centrosomal, pericentriolar material and an increase in total levels of intracellular insulin. RNAi- mediated silencing of pericentrin in secretory β-cells caused dysregulated secretory vesicle hypersecretion of insulin into the media. Together, these data suggest that pericentrin may regulate the intracellular distribution and secretion of insulin. Mice transplanted with pericentrin-depleted islets exhibited abnormal fasting hypoglycemia and inability to regulate blood glucose normally during a glucose challenge, which is consistent with our in vitro data. This previously unrecognized function for a centrosomal protein to mediate vesicle docking in secretory endocrine cells emphasizes the adaptability of these scaffolding proteins to regulate diverse cellular processes and identifies a novel target for modulating regulated protein secretion in disorders such as diabetes

Depleted 15N in hydrolysable-N of arctic soils and its implication for mycorrhizal fungi–plant interaction

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Biogeochemistry 97 (2009): 183-194, doi:10.1007/s10533-009-9365-1.Uptake of nitrogen (N) via root-mycorrhizal associations accounts for a significant portion of total N supply to many vascular plants. Using stable isotope ratios (δ15N) and the mass balance among N pools of plants, fungal tissues, and soils, a number of efforts have been made in recent years to quantify the flux of N from mycorrhizal fungi to host plants. Current estimates of this flux for arctic tundra ecosystems rely on the untested assumption that the δ15N of labile organic N taken up by the fungi is approximately the same as the δ15N of bulk soil. We report here hydrolysable amino acids are more depleted in 15N relative to hydrolysable ammonium and amino sugars in arctic tundra soils near Toolik Lake, Alaska, USA. We demonstrate, using a case study, that recognizing the depletion in 15N for hydrolysable amino acids (δ15N = -5.6 ‰ on average) would alter recent estimates of N flux between mycorrhizal fungi and host plants in an arctic tundra ecosystem.This study was funded by NSF-DEB-0423385and NSF-DEB 0444592. Additional support was provided by Arctic Long Term Ecological Research program, funded by National Science Foundation, Division of Environmental Biology