Non-major-histocompatibility-complex genetics of ankylosing spondylitis

There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-1 gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-1A. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.

Allergen capture by IgE and IgG enhanced cell-binding by allergen multimers: How complex is it?

Allergic diseases are the most common chronic disease of the western world, costing $7.8 billion per year in lost productivity and medical care in Australia alone.1 IgE is central to the immunopathogenesis of allergic diseases and important advances are now being made on multiple fronts of IgE research. In particular, two groups independently invested in the generation of IgE reporter mice to address the vexing question of the route of development of the elusive IgE+ B cell.2, 3 Two new anti-IgE mAb targeting membrane IgE and cell-bound IgE have the potential to deplete the cellular source of IgE.4, 5 These could be candidates for alternative anti-IgE treatment options with advantages over current anti-IgE therapy (OmalizumAb), which depletes free serum IgE. Researchers are still intrigued by the modes of interaction of IgE with allergen, and with both its receptors; the high affinity FcεR1 on mast cells and basophils, and the low affinity, C-type lectin, IgE receptor, CD23,6 on B cells and monocytes (Figure 1a and b). A new approach to the study of the complexity of these interactions was recently reported by Reginald et al.7 on page 167 of this issue.

Synthesis and luminescent properties of star-burst D-Pi-A compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms

Two new star-burst compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms (1a and 1b) were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. Both compounds exhibit strong 1π–π⁎ transitions in the UV region and intense 1π–π⁎/intramolecular charge transfer (1ICT) absorption bands in the UV–vis region. Introducing the carbazole end-capped phenylene ethynylene arm on the 1,3,5-triazine core causes a slight bathochromic shift and enhanced molar extinction coefficient of the 1π–π⁎/1ICT transition band. Both compounds are emissive in solution at room temperature and 77 K, which exhibit pronounced positive solvatochromic effect. The emitting state could be ascribed to 1ICT state in more polar solvent, and 1π–π⁎ state in low-polarity solvent. The high emission quantum yields (Φem=0.90~1.0) of 1a and 1b (in hexane and toluene) make them potential candidates as efficient light-emitting materials. The spectroscopic studies and theoretical calculations indicate that the photophysical properties of these compounds can be tuned by the carbazole end-capped phenylene ethynylene arm, which would also be useful for rational design of photofunctional materials.

Evidence-based recommendations for the diagnosis of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

• As part of the 3E program, we conducted a systematic literature review and gathered consensus from 23 practising Australian rheumatologists to develop guidelines for early identification of ankylosing spondylitis and specialist referral. • In three rounds of break-out sessions followed by discussion and voting, the specialist panel addressed three questions related to diagnosis of ankylosing spondylitis: In individuals with back pain, what are the early clinical features that suggest ankylosing spondylitis? How useful is imaging in identifying early ankylosing spondylitis? Based on which clinical features should a general practitioner refer a patient to a rheumatologist for further evaluation? • The panel agreed on six recommendations related to the three questions: 1a. Early clinical features to suggest ankylosing spondylitis include inflammatory back pain and age at symptom onset < 45 years. 1b. The absence of symptomatic response to an appropriate course of non-steroidal anti-inflammatory drugs makes the diagnosis of ankylosing spondylitis less likely. 1c. Raised inflammatory markers are supportive, but their absence does not rule out the diagnosis of ankylosing spondylitis. 2a. Despite low sensitivity to detect changes of early ankylosing spondylitis, plain radiographs of the pelvis and spine are appropriate initial imaging techniques. 2b. Magnetic resonance imaging is a useful imaging modality for detecting early changes of ankylosing spondylitis. 3. Individuals with inflammatory back pain should be referred to a rheumatologist for further evaluation. • Effective dissemination and implementation of these recommendations are important to standardise the approach to early diagnosis of ankylosing spondylitis.

An asymmetric homodinuclear complex containing the mu-x-oxobis(mu-x-carboxylato)diruthenium(III) core: X-ray structure of [Ru20(o2ec6H4-p-OMe)3(en) (PPh3)2] (C104)" 3CHC13

Asymmetric tri-bridged diruthenium(III) complexes, [Ru2O(O(2)CR)(3)(en) (PPh(3))(2)](ClO4) (R = C6H4-p-X: X = OMe (1a), Me (1b); en=1,2-diaminoethane), were prepared and structurally characterized. Complex 1a 3CHCl(3), crystallizes in the triclinic space group P (1) over bar with a = 14.029(5), b = 14.205(5), c = 20.610(6) Angstrom, alpha= 107.26(3), beta = 101.84(3), gamma= 97.57(3)degrees, V= 3756(2) Angstrom(3) and Z = 2. The complex has an {Ru-2(mu-O)(mu-O(2)CR)(2)(2+)} core and exhibits [O4PRu(mu-O)RuPO2N2](+) coordination environments for the metal centers. The novel structural feature is the asymmetric arrangement of ligands at the terminal sites of the core which shows an Ru... Ru separation of 3.226(3) Angstrom and an Ru-O-Ru angle of 119.2(5)degrees. An intense visible band observed near 570 nm is assigned to a charge transfer transition involving the d pi-Ru(III) and p pi-mu-O Orbitals. Cyclic voltammetry of the complexes displays a reversible Ru-2(III,III) reversible arrow Ru-2(III,IV) couple near 0.8 V (versus SCE) in MeCN-0.1 M TBAP.

Ultrafast Raman loss spectroscopy

This paper deals with a new form of nonlinear Raman spectroscopy called `ultrafast Raman loss spectroscopy (URLS)'. URLS is analogous to stimulated Raman spectroscopy (SRS) but is much more sensitive than SRS. The signals are background (noise) free unlike in coherent anti-Stokes Raman spectroscopy (CARS) and it provides natural fluorescence rejection, which is a major problem in Raman spectroscopy. In addition, being a self-phase matching process, the URLS experiment is much easier than CARS, which requires specific phase matching of the laser pulses. URLS is expected to be alternative if not competitive to CARS microscopy, which has become a popular technique in applications to materials, biology and medicine.

Acid-catalysed cyclisations: structures of novel products isolated in the reaction of 2-[3-(2,6-dimethoxyphenyl)but-2-enyl]-2-methylcyclopentane-1,3-dione with MeOH-HCl

Reaction of the title compound (1a) with anhydrous MeOH-HCl gave 2-endo-(2,6-dimethoxyphenyl)-2-exo-methyl-5-methylbicyclo[3.2.1]octane-6,8-dione (3a), 1,5,14-timethoxy-5,8-seco-6,7-dinorestra-1,3,5(10),9(11)-tetraen-17-one (4), 1,5-dimethoxy-5,8-seco-6,7-dinorestra-1,3,5(10),8,14-pentaen-17-one (5), and 3,4,5,6-tetrahydro-2,7-dimethoxy-3,6-dimethyl-3,2,6-(13-oxopropan[1]yI[3]ylidene)-2H-1-benzoxocin (6). Structures assigned to compounds (3a), (4), and (6) are based on spectral data. The exo-tricyclic acetal structure (6) was further confirmed by the analysis of the 1H n.m.r. spectra of the isomeric alcohols (11) and (12), obtained by sodium borohydride reduction of (6).

Efficient designs for sampling and subsampling in fisheries research based on ranked sets

Sampling strategies are developed based on the idea of ranked set sampling (RSS) to increase efficiency and therefore to reduce the cost of sampling in fishery research. The RSS incorporates information on concomitant variables that are correlated with the variable of interest in the selection of samples. For example, estimating a monitoring survey abundance index would be more efficient if the sampling sites were selected based on the information from previous surveys or catch rates of the fishery. We use two practical fishery examples to demonstrate the approach: site selection for a fishery-independent monitoring survey in the Australian northern prawn fishery (NPF) and fish age prediction by simple linear regression modelling a short-lived tropical clupeoid. The relative efficiencies of the new designs were derived analytically and compared with the traditional simple random sampling (SRS). Optimal sampling schemes were measured by different optimality criteria. For the NPF monitoring survey, the efficiency in terms of variance or mean squared errors of the estimated mean abundance index ranged from 114 to 199% compared with the SRS. In the case of a fish ageing study for Tenualosa ilisha in Bangladesh, the efficiency of age prediction from fish body weight reached 140%.

Efficient regression analysis with ranked-set sampling

This article is motivated by a lung cancer study where a regression model is involved and the response variable is too expensive to measure but the predictor variable can be measured easily with relatively negligible cost. This situation occurs quite often in medical studies, quantitative genetics, and ecological and environmental studies. In this article, by using the idea of ranked-set sampling (RSS), we develop sampling strategies that can reduce cost and increase efficiency of the regression analysis for the above-mentioned situation. The developed method is applied retrospectively to a lung cancer study. In the lung cancer study, the interest is to investigate the association between smoking status and three biomarkers: polyphenol DNA adducts, micronuclei, and sister chromatic exchanges. Optimal sampling schemes with different optimality criteria such as A-, D-, and integrated mean square error (IMSE)-optimality are considered in the application. With set size 10 in RSS, the improvement of the optimal schemes over simple random sampling (SRS) is great. For instance, by using the optimal scheme with IMSE-optimality, the IMSEs of the estimated regression functions for the three biomarkers are reduced to about half of those incurred by using SRS.

Partial intervertebral fusion secures successful outcomes after thoracoscopic anterior scoliosis correction: A low-dose computed tomography study

Study Design Retrospective review of prospectively collected data. Objectives To analyze intervertebral (IV) fusion after thoracoscopic anterior spinal fusion (TASF) and explore the relationship between fusion scores and key clinical variables. Summary of Background Information TASF provides comparable correction with some advantages over posterior approaches but reported mechanical complications, and their relationship to non-union and graft material is unclear. Similarly, the optimal combination of graft type and implant stiffness for effecting successful radiologic union remains undetermined. Methods A subset of patients from a large single-center series who had TASF for progressive scoliosis underwent low-dose computed tomographic scans 2 years after surgery. The IV fusion mass in the disc space was assessed using the 4-point Sucato scale, where 1 indicates <50% and 4 indicates 100% bony fusion of the disc space. The effects of rod diameter, rod material, graft type, fusion level, and mechanical complications on fusion scores were assessed. Results Forty-three patients with right thoracic major curves (mean age 14.9 years) participated in the study. Mean fusion scores for patient subgroups ranged from 1.0 (IV levels with rod fractures) to 2.2 (4.5-mm rod with allograft), with scores tending to decrease with increasing rod size and stiffness. Graft type (autograft vs. allograft) did not affect fusion scores. Fusion scores were highest in the middle levels of the rod construct (mean 2.52), dropping off by 20% to 30% toward the upper and lower extremities of the rod. IV levels where a rod fractured had lower overall mean fusion scores compared to levels without a fracture. Mean total Scoliosis Research Society (SRS) questionnaire scores were 98.9 from a possible total of 120, indicating a good level of patient satisfaction. Conclusions Results suggest that 100% radiologic fusion of the entire disc space is not necessary for successful clinical outcomes following thoracoscopic anterior selective thoracic fusion.