Abundance estimation from multiple photo surveys: confidence distributions and reduced likelihoods for bowhead whales off Alaska

Maximum likelihood estimates of abundance are obtained from repeated photographic surveys of a closed stratified population with naturally marked and unmarked individuals. Capture intensities are assumed log-linear in stratum, year, and season. In the chosen model, an approximate confidence distribution for total abundance of bowhead whales, with an accompanying likelihood reduced of nuisance parameters, is found from a parametric bootstrap experiment. The confidence distribution depends on the assumed study protocol. A confidence distribution that is exact (except for the effect of discreteness) is found by conditioning in the unstratified case without unmarked individuals.     

Hierarchical spatial modeling of additive and dominance genetic variance for large spatial trial datasets

Summary .  This article expands upon recent interest in Bayesian hierarchical models in quantitative genetics by developing spatial process models for inference on additive and dominance genetic variance within the context of large spatially referenced trial datasets. Direct application of such models to large spatial datasets are, however, computationally infeasible because of cubic-order matrix algorithms involved in estimation. The situation is even worse in Markov chain Monte Carlo (MCMC) contexts where such computations are performed for several iterations. Here, we discuss approaches that help obviate these hurdles without sacrificing the richness in modeling. For genetic effects, we demonstrate how an initial spectral decomposition of the relationship matrices negate the expensive matrix inversions required in previously proposed MCMC methods. For spatial effects, we outline two approaches for circumventing the prohibitively expensive matrix decompositions: the first leverages analytical results from Ornstein–Uhlenbeck processes that yield computationally efficient tridiagonal structures, whereas the second derives a modified predictive process model from the original model by projecting its realizations to a lower-dimensional subspace, thereby reducing the computational burden. We illustrate the proposed methods using a synthetic dataset with additive, dominance, genetic effects and anisotropic spatial residuals, and a large dataset from a Scots pine ( Pinus sylvestris L.) progeny study conducted in northern Sweden. Our approaches enable us to provide a comprehensive analysis of this large trial, which amply demonstrates that, in addition to violating basic assumptions of the linear model, ignoring spatial effects can result in downwardly biased measures of heritability.     

Filter bed systems treating domestic wastewater in the Nordic countries – Performance and reuse of filter media

Nine filter beds have been constructed in the Nordic countries, Denmark, Finland, Norway and Sweden. Filter beds consist of a septic tank followed by an aerobic pre-treatment biofilter and a subsequent saturated flow grass-covered filter. Thus, filter beds are similar to subsurface flow constructed wetlands with pre-treatment biofilters, but do not have wetland plants with roots submerged into the saturated filter. All saturated filters contain Filtralite^®P, a light-weight expanded clay aggregate possessing high phosphorus sorption capacity. The filter bed systems showed stable and consistent performance during the testing period of 3 years. Removal of organic matter measured as biochemical oxygen demand (BOD) was >80%, total phosphorus (TP) >94% and total nitrogen (TN) ranged from 32 to 66%. Effluent concentrations of fecal indicator bacteria met the European bathing water quality criteria in all systems. One system was investigated for virus removal and somatic viruses were not detected in the effluent. The investigations revealed that the majority of the BOD and nitrogen removal occurred in the pre-treatment filters and the phosphorus and bacteria removal was more prominent in the saturated filters. The saturated filters could be built substantially smaller than the current design guidelines without sacrificing treatment performance. The used filter material met the Norwegian regulations for reuse in agriculture with respect to heavy metals, bacteria and parasites. When saturated with phosphorus, the light-weight aggregate, Filtralite^®P used in the saturated bed is a suitable phosphorus fertilizer and additionally has a liming effect.     

Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis – a prospective cohort study

Introduction

Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA).

Methods

In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for six months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analysed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor).

Results

During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (P = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (P = 0.002).

Conclusions

Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.     

Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial): study protocol for a randomised controlled trial

Background

Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation.

Methods/design

We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV₁) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV₁ z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome.

Discussion

The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world’s HIV-infected children live and where HIV-associated CLD is highly prevalent.

Trial registration

ClinicalTrials.gov, NCT02426112. Registered on 21 April 2015.

     

The soluble biomarker calprotectin (a S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab

Introduction  

Calprotectin (MRP8/MRP14, S100A8/A9) is associated with disease activity in patients with rheumatoid arthritis (RA). Ultrasonography (US) is a reliable method for evaluation of synovitis (B-mode (BM) and power Doppler (PD)). The present objectives were to explore in RA patients the associations between calprotectin and a comprehensive US examination, as well as the responsiveness of calprotectin compared to other inflammatory markers during anti-TNF treatment.     

Diet of ringed seals (Pusa hispida) from Northeast Greenland

The diet of ringed seals (Pusa hispida) from coastal and offshore areas of Northeast Greenland was determined by identifying, to the lowest taxonomic limit possible, all hard-part contents from the gastrointestinal tract of 51 seals sampled (2002–2004) in spring (April to June, N = 35) and autumn (September to October, N = 16). The autumn diet was characterized by high numbers of Parathemisto libellula, and the spring diet was comprised primarily of polar cod (Boreogadus saida), with few invertebrates consumed. The coastal seal diet samples had a diverse fish prey composition (during both the spring and autumn), whereas the open water seals had eaten mostly crustaceans with P. libellula being most abundant. The sample sizes from the various locations and seasons were not large enough to explore age-class effects on diet in addition. Similar to earlier studies, this study suggests that the ringed seal is a generalist that exploits prey based on availability, with a few key species dominating the diet in an area at least on a seasonal basis.     

Heavy chains of inter alpha inhibitor (IαI) inhibit the human complement system at early stages of the cascade

Inter alpha inhibitor (IαI) is an abundant serum protein consisting of three polypeptides: two heavy chains (HC1 and HC2) and bikunin, a broad-specificity Kunitz-type proteinase inhibitor. The complex is covalently held together by chondroitin sulfate but during inflammation IαI may interact with TNF-stimulated gene 6 protein (TSG-6), which supports transesterification of heavy chains to hyaluronan. Recently, IαI was shown to inhibit mouse complement in vivo and to protect from complement-mediated lung injury but the mechanism of such activity was not elucidated. Using human serum depleted from IαI, we found that IαI is not an essential human complement inhibitor as was reported for mice and that such serum has unaltered hemolytic activity. However, purified human IαI inhibited classical, lectin and alternative complement pathways in vitro when added in excess to human serum. The inhibitory activity was dependent on heavy chains but not bikunin and detected at the level of initiating molecules (MBL, properdin) in the lectin/alternative pathways or C4b in the classical pathway. Furthermore, IαI affected formation and assembly of the C1 complex and prevented assembly of the classical pathway C3-convertase. Presence and putative interactions with TSG-6 did not affect the ability of IαI to inhibit complement thus implicating IαI as a potentially important complement inhibitor once enriched onto hyaluronan moieties in the course of local inflammatory processes. In support of this, we found a correlation between IαI/HC-containing proteins and hemolytic activity of synovial fluid from patients suffering from rheumatoid arthritis.     

Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites

The rhodium(II)-catalyzed intermolecular C-H insertion of methyl aryldiazoacetates with either N-Boc-piperidine or N-Boc-pyrrolidine followed by deprotection with trifluoroacetic acid is a very direct method for the synthesis of methylphenidate analogues. By using either dirhodium tetraacetate or dirhodium tetraprolinate derivatives as catalyst, either the racemic or enantioenriched methylphenidate analogues can be prepared. The binding affinities of the methylphenidate analogues to both the dopamine and the serotonin transporters are described. The most notable compounds are the erythro-(2-naphthyl) analogues which display high binding affinity and selectivity for the serotonin transporter.