Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. METHODS: Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used RESULTS: Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05). CONCLUSION: Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation

RecA-mediated strand invasion of DNA by oligonucleotides substituted with 2-aminoadenine and 2-thiothymine

Sequence-specific recognition of DNA is a critical step in gene targeting. Here we describe unique oligonucleotide (ON) hybrids that can stably pair to both strands of a linear DNA target in a RecA-dependent reaction with ATP or ATPγS. One strand of the hybrids is a 30-mer DNA ON that contains a 15-nt-long A/T-rich central core. The core sequence, which is substituted with 2-aminoadenine and 2-thiothymine, is weakly hybridized to complementary locked nucleic acid or 2′-OMe RNA ONs that are also substituted with the same base analogs. Robust targeting reactions took place in the presence of ATPγS and generated metastable double D-loop joints. Since the hybrids had pseudocomplementary character, the component ONs hybridized less strongly to each other than to complementary target DNA sequences composed of regular bases. This difference in pairing strength promoted the formation of joints capable of accommodating a single mismatch. If similar joints can form in vivo, virtually any A/T-rich site in genomic DNA could be selectively targeted. By designing the constructs so that the DNA ON is mismatched to its complementary sequence in DNA, joint formation might allow the ON to function as a template for targeted point mutation and gene correction

Deliberating stratospheric aerosols for climate geoengineering and the SPICE project

Increasing concerns about the narrowing window for averting dangerous climate change have prompted calls for research into geoengineering, alongside dialogue with the public regarding this as a possible response. We report results of the first public engagement study to explore the ethics and acceptability of stratospheric aerosol technology and a proposed field trial (the Stratospheric Particle Injection for Climate Engineering (SPICE) ‘pipe and balloon’ test bed) of components for an aerosol deployment mechanism. Although almost all of our participants were willing to allow the field trial to proceed, very few were comfortable with using stratospheric aerosols. This Perspective also discusses how these findings were used in a responsible innovation process for the SPICE project initiated by the UK’s research councils

Modelling diverse root density dynamics and deep nitrogen uptake — a simple approach

We present a 2-D model for simulation of root density and plant nitrogen (N) uptake for crops grown in agricultural systems, based on a modification of the root density equation originally proposed by Gerwitz and Page in J Appl Ecol 11:773–781, (1974). A root system form parameter was introduced to describe the distribution of root length vertically and horizontally in the soil profile. The form parameter can vary from 0 where root density is evenly distributed through the soil profile, to 8 where practically all roots are found near the surface. The root model has other components describing root features, such as specific root length and plant N uptake kinetics. The same approach is used to distribute root length horizontally, allowing simulation of root growth and plant N uptake in row crops. The rooting depth penetration rate and depth distribution of root density were found to be the most important parameters controlling crop N uptake from deeper soil layers. The validity of the root distribution model was tested with field data for white cabbage, red beet, and leek. The model was able to simulate very different root distributions, but it was not able to simulate increasing root density with depth as seen in the experimental results for white cabbage. The model was able to simulate N depletion in different soil layers in two field studies. One included vegetable crops with very different rooting depths and the other compared effects of spring wheat and winter wheat. In both experiments variation in spring soil N availability and depth distribution was varied by the use of cover crops. This shows the model sensitivity to the form parameter value and the ability of the model to reproduce N depletion in soil layers. This work shows that the relatively simple root model developed, driven by degree days and simulated crop growth, can be used to simulate crop soil N uptake and depletion appropriately in low N input crop production systems, with a requirement of few measured parameters

Kitaev's quantum double model from a local quantum physics point of view

A prominent example of a topologically ordered system is Kitaev's quantum double model $\mathcal{D}(G)$ for finite groups $G$ (which in particular includes $G = \mathbb{Z}_2$, the toric code). We will look at these models from the point of view of local quantum physics. In particular, we will review how in the abelian case, one can do a Doplicher-Haag-Roberts analysis to study the different superselection sectors of the model. In this way one finds that the charges are in one-to-one correspondence with the representations of $\mathcal{D}(G)$, and that they are in fact anyons. Interchanging two of such anyons gives a non-trivial phase, not just a possible sign change. The case of non-abelian groups $G$ is more complicated. We outline how one could use amplimorphisms, that is, morphisms $A \to M_n(A)$ to study the superselection structure in that case. Finally, we give a brief overview of applications of topologically ordered systems to the field of quantum computation.Comment: Chapter contributed to R. Brunetti, C. Dappiaggi, K. Fredenhagen, J. Yngvason (eds), Advances in Algebraic Quantum Field Theory (Springer 2015). Mainly revie

Bayesian estimates of linkage disequilibrium

[Background] The maximum likelihood estimator of D' – a standard measure of linkage disequilibrium – is biased toward disequilibrium, and the bias is particularly evident in small samples and rare haplotypes. [Results] This paper proposes a Bayesian estimation of D' to address this problem. The reduction of the bias is achieved by using a prior distribution on the pair-wise associations between single nucleotide polymorphisms (SNP)s that increases the likelihood of equilibrium with increasing physical distances between pairs of SNPs. We show how to compute the Bayesian estimate using a stochastic estimation based on MCMC methods, and also propose a numerical approximation to the Bayesian estimates that can be used to estimate patterns of LD in large datasets of SNPs. [Conclusion] Our Bayesian estimator of D' corrects the bias toward disequilibrium that affects the maximum likelihood estimator. A consequence of this feature is a more objective view about the extent of linkage disequilibrium in the human genome, and a more realistic number of tagging SNPs to fully exploit the power of genome wide association studies.Research supported by NIH/NHLBI grant R21 HL080463-01, NIH/NIDDK 1R01DK069646-01A1 and the Spanish research program [projects TIN2004-06204-C03-02 and TIN2005-02516]

An unusual case of chronic meningitis

BACKGROUND: Chronic meningitis is defined as symptoms and signs of meningeal inflammation and persisting cerebrospinal fluid abnormalities such as elevated protein level and pleocytosis for at least one month. CASE PRESENTATION: A 62-year-old woman, of unremarkable past medical history, was admitted to hospital for investigation of a four-week history of vomiting, malaise an associated hyponatraemia. She had a low-grade pyrexia with normal inflammatory markers. A CT brain was unremarkable and a contrast MRI brain revealed sub-acute infarction of the right frontal cortex but with no evidence of meningeal enhancement. Due to increasing confusion and patient clinical deterioration a lumbar puncture was performed at 17 days post admission. This revealed gram-negative coccobacilli in the CSF, which was identified as Neisseria meningitidis group B. The patient made a dramatic recovery with high-dose intravenous ceftriaxone antibiotic therapy for meningococcal meningitis. CONCLUSIONS: 1) Chronic bacterial meningitis may present highly atypically, particularly in the older adult. 2) There may be an absent or reduced febrile response, without a rise in inflammatory markers, despite a very unwell patient. 3) Early lumbar puncture is to be encouraged as it is essential to confirm the diagnosis.4) Despite a delayed diagnosis appropriate antibiotic therapy can still lead to a good outcome

Health-seeking behaviour of human brucellosis cases in rural Tanzania

<p>Abstract</p> <p>Background</p> <p>Brucellosis is known to cause debilitating conditions if not promptly treated. In some rural areas of Tanzania however, practitioners give evidence of seeing brucellosis cases with symptoms of long duration. The purpose of this study was to establish health-seeking behaviour of human brucellosis cases in rural Tanzania and explore the most feasible ways to improve it.</p> <p>Methods</p> <p>This was designed as a longitudinal study. Socio-demographic, clinical and laboratory data were collected from patients who reported to selected hospitals in rural northern Tanzania between June 2002 and April 2003. All patients with conditions suspicious of brucellosis on the basis of preliminary clinical examination and history were enrolled into the study as brucellosis suspects. Blood samples were taken and tested for brucellosis using the Rose-Bengal Plate Test (RBPT) and other agglutination tests available at the health facilities and the competitive ELISA (c-ELISA) test at the Veterinary Laboratory Agencies (VLA) in the UK. All suspects who tested positive with the c-ELISA test were regarded as brucellosis cases. A follow-up of 49 cases was made to collect data on health-seeking behaviour of human brucellosis cases.</p> <p>Results</p> <p>The majority of cases 87.7% gave a history of going to hospital as the first point of care, 10.2% purchased drugs from a nearby drug shop before going to hospital and 2% went to a local traditional healer first. Brucellosis cases delayed going to hospital with a median delay time of 90 days, and with 20% of the cases presenting to hospitals more than a year after the onset of symptoms. Distance to the hospital, keeping animals and knowledge of brucellosis were significantly associated with patient delay to present to hospital.</p> <p>Conclusion</p> <p>More efforts need to be put on improving the accessibility of health facilities to the rural poor people who succumb to most of the diseases including zoonoses. Health education on brucellosis in Tanzania should also stress the importance of early presentation to hospitals for prompt treatment.</p

Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular germ cell tumours (TGCT). In a previous study, we examined the gene expression profile of CIS cells and found many features common to embryonic stem cells indicating that initiation of neoplastic transformation into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM and a sample containing a mixture of N-SEM components, and analyse the data together with the previously published data on CIS. Genes showing expression in the SEM or N-SEM were selected, in order to identify gene expression markers associated with the progression of CIS cells. The identified markers were verified by reverse transcriptase–polymerase chain reaction and in situ hybridisation in a range of different TGCT samples. Verification showed some interpatient variation, but combined analysis of a range of the identified markers may discriminate TGCT samples as SEMs or N-SEMs. Of particular interest, we found that both DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta) and DNMT3L (DNA (cytosine-5-)-methyltransferase 3 like) were overexpressed in the N-SEMs, indicating the epigenetic differences between N-SEMs and classical SEM