Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 �� 10-8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 �� 10-6 overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

Adsorption of p-nitrophenol on organoclays

In this study, organoclays were prepared through ion exchange of a single cationic surfactant, hexadecyltrimethylammonium bromide and characterised by a range of methods including X-ray diffraction (XRD) and thermogravimetric analysis. Changes in the surface properties of montmorillonite and the organoclays were observed and the basal spacings of organoclays with and without p-nitrophenol were determined using XRD. The thermal stability of both organoclays were measured using thermogravimetry. As the surfactant loading increased, the expanded basal spacings were observed, and different molecular configurations of surfactant were identified. When the surfactant loading exceeded 1.0 CEC, surfactant molecules tend to adsorb strongly on the clay surface and this resulted in increased affinity to organic compounds. The adsorbed p-nitrophenol and the surfactant decomposed simultaneously. Hence, the surfactant molecules and adsorbed p-nitrophenol are important in determining the thermal stabilities of organoclays. This study enhances the understanding of the structure and adsorption properties of organoclays and has further implications for the application of organoclays as filter materials for the removal of organic pollutants in aqueous solutions.

Electronic states of trans-polyacetylene, poly(p-phenylene vinylene) and sp-hybridised carbon species in amorphous hydrogenated carbon probed by resonant Raman scattering

Inclusions of sp-hybridised, trans-polyacetylene [trans-(CH)x] and poly(p-phenylene vinylene) (PPV) chains are revealed using resonant Raman scattering (RRS) investigation of amorphous hydrogenated carbon (a-C:H) films in the near IR ��� UV range. The RRS spectra of trans-(CH)x core Ag modes and the PPV CC-H phenylene mode are found to transform and disperse as the laser excitation energy ����L is increased from near IR through visible to UV, whereas sp-bonded inclusions only become evident in UV. This is attributed to ����L probing of trans-(CH)x chain inhomogeneity and the distribution of chains with varying conjugation length; for PPV to the resonant probing of phelynene ring disorder; and for sp segments, to ����L probing of a local band gap of end-terminated polyynes. The IR spectra analysis confirmed the presence of sp, trans-(CH)x and PPV inclusions. The obtained RRS results for a-C:H denote differentiation between the core Ag trans-(CH)x modes and the PPV phenylene mode. Furthermore, it was found that at various laser excitation energies the changes in Raman spectra features for trans-(CH)x segments included in an amorphous carbon matrix are the same as in bulk trans-polyacetylene. The latter finding can be used to facilitate identification of trans-(CH)x in the spectra of complex carbonaceous materials.

Levelling expectations across different years in an undergraduate degree to support work-related learning : evidence for a multi-pronged approach.

One of the ways in which university departments and faculties can enhance the quality of learning and assessment is to develop a ���well thought out criterion���referenced assessment system��� (Biggs, 2003, p. 271). In designing undergraduate degrees (courses) this entails making decisions about the levelling of expectations across different years through devising objectives and their corresponding criteria and standards: a process of alignment analogous to what happens in unit (subject) design. These decisions about levelling have important repercussions in terms of supporting students��� work���related learning, especially in relation to their ability to cope with the increasing cognitive and skill demands made on them as they progress through their studies. They also affect the accountability of teacher judgments of students��� responses to assessment tasks, achievement of unit objectives and, ultimately, whether students are awarded their degrees and are sufficiently prepared for the world of work. Research reveals that this decision���making process is rarely underpinned by an explicit educational rationale (Morgan et al, 2002). The decision to implement criterion referenced assessment in an undergraduate microbiology degree was the impetus for developing such a rationale because of the implications for alignment, and therefore ���levelling��� of expectations across different years of the degree. This paper provides supporting evidence for a multi���pronged approach to levelling, through backward mapping of two revised units (foundation and exit year). This approach adheres to the principles of alignment while combining a work���related approach (via industry input) with the blended disciplinary and learner���centred approaches proposed by Morgan et al. (2002). It is suggested that this multi���pronged approach has the potential for making expectations, especially work���related ones across different year levels of degrees, more explicit to students and future employers.

Patterns of fitting cosmetically tinted contact lenses

Cosmetically tinted soft contact lenses are an attractive option for contact lens wearers. Data that we have gathered from annual contact lens fitting surveys demonstrate that those wearing tinted lenses are more likely to be female (4.6% of all soft lenses fitted vs. 1.6% for males; p < 0.0001) and younger (27 11 years vs. 33 13 years for those wearing non-tinted lenses; p < 0.0001). Tinted lenses tend to be worn more on a part-time basis and are replaced less frequently than non-tinted lenses. The decline in fitting tinted lenses over the past 12 years may be due to (a) the current limited availability of tinted lenses in silicone hydrogel materials and daily disposable replacement frequencies, which together represent a significant majority (78%) of new soft lenses fits today, (b) growing concerns among lens wearers and practitioners relating to the risks of complications associated with the wearing of tinted lenses, and (c) reduced promotion of such lenses by the contact lens industry.

Are combination forecasts of S&P 500 volatility statistically superior?

Forecasting volatility has received a great deal of research attention, with the relative performances of econometric model based and option implied volatility forecasts often being considered. While many studies find that implied volatility is the pre-ferred approach, a number of issues remain unresolved, including the relative merit of combining forecasts and whether the relative performances of various forecasts are statistically different. By utilising recent econometric advances, this paper considers whether combination forecasts of S&P 500 volatility are statistically superior to a wide range of model based forecasts and implied volatility. It is found that a combination of model based forecasts is the dominant approach, indicating that the implied volatility cannot simply be viewed as a combination of various model based forecasts. Therefore, while often viewed as a superior volatility forecast, the implied volatility is in fact an inferior forecast of S&P 500 volatility relative to model-based forecasts.

Practitioner influence on contact lens prescribing in the UK

Contact lenses are mainly fitted by registered optometrists and contact lens opticians in the UK. Data we have gathered from annual contact lens fitting surveys over the past 12 years indicate that, on average, registered optometrists and contact lens opticians undertake 3.2 and 7.1 contact lens fits per week (p < 0.0001). More experienced practitioners tend to fit older patients. Practitioners fitting more lenses per year tend to fit a higher proportion of soft lenses. Contact lens opticians tend to fit a higher proportion of patients with planned replacement and daily disposable lenses compared with optometrists.

The jump component of S&P 500 volatility and the VIX index

Much research has investigated the differences between option implied volatilities and econometric model-based forecasts. Implied volatility is a market determined forecast, in contrast to model-based forecasts that employ some degree of smoothing of past volatility to generate forecasts. Implied volatility has the potential to reflect information that a model-based forecast could not. This paper considers two issues relating to the informational content of the S&P 500 VIX implied volatility index. First, whether it subsumes information on how historical jump activity contributed to the price volatility, followed by whether the VIX reflects any incremental information pertaining to future jump activity relative to model-based forecasts. It is found that the VIX index both subsumes information relating to past jump contributions to total volatility and reflects incremental information pertaining to future jump activity. This issue has not been examined previously and expands our understanding of how option markets form their volatility forecasts.

Everyday life and the edges of existence : wrongs with no name or the wrong name?

Actions for wrongful life, as they have come unfortunately to be styled, encompass various types of claim. These include claims for alleged negligence after conception, those based on negligent advice or diagnosis prior to conception concerning possible effects of treatment given to the child's mother, contraception or sterilisation, or genetic disability. This distinguishes such claims from those for so called wrongful birth, which are claims by parents for the cost of raising either a healthy or a disabled child where the unplanned birth imposes costs on the parents as a result of clinical negligence. Two of the more controversial cases to have reached the High Court of Australia which are if interest to us here in the past decade are Cattanach v Melchior where the court, by a narrow majority (McHugh, Gummow, Kirby and Callinan JJ; Gleeson CJ, Hayne and Heydon dissenting) acknowledged recovery for wrongful birth. In the second joined appeals of Harriton v Stephens and Waller v James; Waller v Hoolahan the court overwhelmingly precluded a ���wrongful life��� claim (Gleeson CJ, Gummow, Hayne, Callinan, Heydon and Crennan JJ; Kirby J dissenting). Both cases raised issues around the sanctity and value of life and the nature of harm and the assessment of damages, and this brief note affords us the opportunity to consider the way in which the ���life as legal loss��� arguments were treated by the various judges in both cases.