Mutational Analysis of the Rhodopsin Gene in Sector Retinitis Pigmentosa

Background: To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland.

Design: A case series of sector RP in a tertiary ocular genetics clinic.

Participants: Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent.

Methods: The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced.

Main Outcome Measure: Rhodopsin mutational status.

Results: A heterozygous missense mutation in RHO (c.173C > T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO.

Conclusions: The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.

The continued salience of religious voting in the United States, Germany, and Great Britain

Conventional wisdom on party systems in advanced industrial democracies holds that modern electorates are dealigned and that social cleavages no longer structure party politics. Recent work on class cleavages has challenged this stylized fact. The analysis performed here extends this criticism to the religious-secular cleavage. Using path analysis and comparing the current electorates of the United States, Germany, and Great Britain with the early 1960s, this paper demonstrates that the religious-secular cleavage remains or has become a significant predictor of conservative vote choice. While the effects of the religious-secular cleavage on vote choice have become largely indirect, the total of the direct and indirect effects is substantial and equivalent to the effects of class and status.

A European Culture War in the Twentieth Century? Antic-Catholicism and Anti-Bolshevism between Moscow, Berlin, and the Vatican 1922 to 1933

The term “culture war” has become a generic expression for secular-catholic conflicts across nineteenth-century Europe. Yet, if measured by acts of violence, anticlericalism peaked in the years between 1927 and 1939, when thousands of Catholic priests and believers were imprisoned or executed and hundreds of churches razed in Mexico, Spain and Russia. This essay argues that not only in these three countries, but indeed across Europe a culture war raged in the interwar period. It takes, as a case study, the interaction of communist and Catholic actors located in the Vatican, the Soviet Union, and Germany in the period between the beginning of the Pontificate of Pius XI in 1922 and Hitler’s appointment as chancellor of Germany in 1933. Using correspondence and reports from the Vatican archives, this essay shows how Papal officials and communist leaders each sought to mobilize the German populace to achieve their own diplomatic ends. German Catholics and communists gladly responded to the call to arms that sounded from Rome and Moscow in 1930, but they did so also to further their own domestic goals. The case study shows how national contexts inflected the transnational dynamics of radical anti-Catholicism in interwar Europe. In the end, agitation against “godlessness” did not lead to the return of a “Christian State” desired by many conservative Christians. Instead, the culture war further destabilized the republic and added a religious dimension to a landscape well suited to National Socialist efforts to reach a Christian population otherwise mistrustful of its völkisch and anticlerical elements.

A contentious subject

Abortion is a contentious subject for any nation and this is no less true of Northern Ireland (NI). Despite being part of the United Kingdom, NI has never enacted the Abortion Act 1967 and the reasons given are our historically conservative attitudes and beliefs. In April 2013 the latest in a series of draft guidelines entitled ‘The Limited Circumstances for a Lawful Termination of Pregnancy in Northern Ireland’ was issued by the Department of Health NI to clarify aspects of earlier versions that were revoked following challenges by pro-life groups on their accuracy and application. That draft guidelines exist at all is down to pressure placed on the Department of Health NI by the fpaNI through the NI Courts.

Is there a common water-activity limit for the three domains of life?

Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a_w) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650–0.605 a_w. Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a_w). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 a_w for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (~0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a_w for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life.

Current-induced forces: a simple derivation

We revisit the problem of forces on atoms under current in nanoscale conductors. We derive and discuss the five principal kinds of force under steady-state conditions from a simple standpoint that—with the help of background literature—should be accessible to physics undergraduates. The discussion aims at combining methodology with an emphasis on the underlying physics through examples. We discuss and compare two forces present only under current—the non-conservative electron wind force and a Lorentz-like velocity-dependent force. It is shown that in metallic nanowires both display significant features at the wire surface, making it a candidate for the nucleation of current-driven structural transformations and failure. Finally we discuss the problem of force noise and the limitations of Ehrenfest dynamics

A Bayesian method for detecting stellar flares

We present a Bayesian-odds-ratio-based algorithm for detecting stellar flares in light-curve data. We assume flares are described by a model in which there is a rapid rise with a half-Gaussian profile, followed by an exponential decay. Our signal model also contains a polynomial background model required to fit underlying light-curve variations in the data, which could otherwise partially mimic a flare. We characterize the false alarm probability and efficiency of this method under the assumption that any unmodelled noise in the data is Gaussian, and compare it with a simpler thresholding method based on that used in Walkowicz et al. We find our method has a significant increase in detection efficiency for low signal-to-noise ratio (S/N) flares. For a conservative false alarm probability our method can detect 95 per cent of flares with S/N less than 20, as compared to S/N of 25 for the simpler method. We also test how well the assumption of Gaussian noise holds by applying the method to a selection of 'quiet' Kepler stars. As an example we have applied our method to a selection of stars in Kepler Quarter 1 data. The method finds 687 flaring stars with a total of 1873 flares after vetos have been applied. For these flares we have made preliminary characterizations of their durations and and S/N.

The Collapse Behaviour of Cold-formed Steel Portal Frames at Elevated Temperatures

This paper describes the results of non-linear elasto-plastic implicit dynamic finite element analyses that are used to predict the collapse behaviour of cold-formed steel portal frames at elevated temperatures. The collapse behaviour of a simple rigid-jointed beam idealisation and a more accurate semi-rigid jointed shell element idealisation are compared for two different fire scenarios. For the case of the shell element idealisation, the semi-rigidity of the cold-formed steel joints is explicitly taken into account through modelling of the bolt-hole elongation stiffness. In addition, the shell element idealisation is able to capture buckling of the cold-formed steel sections in the vicinity of the joints. The shell element idealisation is validated at ambient temperature against the results of full-scale tests reported in the literature. The behaviour at elevated temperatures is then considered for both the semi-rigid jointed shell and rigid-jointed beam idealisations. The inclusion of accurate joint rigidity and geometric non-linearity (second order analysis) are shown to affect the collapse behaviour at elevated temperatures. For each fire scenario considered, the importance of base fixity in preventing an undesirable outwards collapse mechanism is demonstrated. The results demonstrate that joint rigidity and varying fire scenarios should be considered in order to allow for conservative design.

Minimal intervention dentistry and older patients part 2: minimally invasive operative interventions

As described in the first paper of this two part series, the expansion of our older population and the concomitant reduction in levels of edentulism will result in an increase in the number of patients presenting in general practice with complex restorative challenges. The application of the concepts of minimal intervention dentistry and minimally invasive operative techniques may offer a powerful armamentarium to the general dentist to provide ethical and conservative treatment to older patients.

Clinical Relevance: When it is unavoidable, operative intervention should be as minimally invasive as practicable in older patients to preserve the longevity of their natural dentition.

Accelerated partial breast irradiation (APBI): Are breath-hold and volumetric radiation therapy techniques useful?

Background: In a selective group of patients accelerated partial breast irradiation (APBI) might be applied after conservative breast surgery to reduce the amount of irradiated healthy tissue. The role of volumetric modulated arc therapy (VMAT) and voluntary moderately deep inspiration breath-hold (vmDIBH) techniques in further reducing irradiated healthy – especially heart – tissue is investigated.

Material and methods: For 37 partial breast planning target volumes (PTVs), three-dimensional conformal radiotherapy (3D-CRT) (3 – 5 coplanar or non-coplanar 6 and/or 10 MV beams) and VMAT (two partial 6 MV arcs) plans were made on CTs acquired in free-breathing (FB) and/or in vmDIBH. Dose-volume parameters for the PTV, heart, lungs, and breasts were compared. 

Results: Better dose conformity was achieved with VMAT compared to 3D-CRT (conformity index 1.24 0.09 vs. 1.49 0.20). Non-PTV ipsilateral breast receiving 50% of the prescribed dose was on average reduced by 28% in VMAT plans compared to 3D-CRT plans. Mean heart dose (MHD) reduced from 2.0 (0.1 – 5.1) Gy in 3D-CRT(FB) to 0.6 (0.1 – 1.6) Gy in VMAT(vmDIBH). VMAT is benefi cial for MHD reduction if MHD with 3D-CRT exceeds 0.5Gy. Cardiac dose reduction as a result of VMAT increases with increasing initial MHD, and adding vmDIBH reduces the cardiac dose further. Mean dose to the ipsilateral lung decreased from 3.7 (0.7 – 8.7) to 1.8 (0.5 – 4.0) Gy with VMAT(vmDIBH) compared to 3D-CRT(FB). VMAT resulted in a slight increase in the contralateral breast dose (DMean ) always remaining 1.9 Gy). 

Conclusions: For APBI patients, VMAT improves PTV dose conformity and delivers lower doses to the ipsilateral breast and lung compared to 3D-CRT. This goes at the cost of a slight but acceptable increase of the contralateral breast dose. VMAT reduces cardiac dose if MHD exceeds 0.5 Gy for 3D-CRT. Adding vmDIBH results in a further reduction of heart and ipsilateral lung dose. 

A tree augmented classifier based on Extreme Imprecise Dirichlet Model

We present TANC, a TAN classifier (tree-augmented naive) based on imprecise probabilities. TANC models prior near-ignorance via the Extreme Imprecise Dirichlet Model (EDM). A first contribution of this paper is the experimental comparison between EDM and the global Imprecise Dirichlet Model using the naive credal classifier (NCC), with the aim of showing that EDM is a sensible approximation of the global IDM. TANC is able to deal with missing data in a conservative manner by considering all possible completions (without assuming them to be missing-at-random), but avoiding an exponential increase of the computational time. By experiments on real data sets, we show that TANC is more reliable than the Bayesian TAN and that it provides better performance compared to previous TANs based on imprecise probabilities. Yet, TANC is sometimes outperformed by NCC because the learned TAN structures are too complex; this calls for novel algorithms for learning the TAN structures, better suited for an imprecise probability classifier.

Decadent Conservatism: Politics and Aesthetics in The Senate

The relationship between late-Victorian Decadence and Aestheticism and politics has long been vexed. This article explores the hitherto under-explored confluence of conservatism and avant-garde literature in the period by introducing The Senate, a Tory-Decadent journal that ran from 1894-7. While Decadent authors occupied various political positions, this article argues that The Senate offers a crucial link between conservatism and Decadence The article presents the journal in its political and publishing context, outlining its editorial position on such issues as the Liberal Unionist-Conservative coalition governments, Britain's relationship with Europe and the threat of ‘State Socialism’, as well as its valorisation of Bollingbroke and eighteenth-century Toryism, and its relationship to, and difference from, key Decadent journals the Yellow Book and The Savoy. It then goes on to articulate its relationship to Decadence by focussing on the presence of Paul Verlaine in its pages and its vitriolic response to the press coverage of Oscar Wilde's trials. The article concludes by exploring the surprising wake of The Senate, briefly tracing the editors' influence in the development of Modernism and links with the journal BLAST.

The Deconstructed Church: Understanding Emerging Christianity

The Emerging Church Movement (ECM) is a reform movement within Western Christianity that reacts against its roots in conservative evangelicalism by “de-constructing” contemporary expressions of Christianity. Emerging Christians see themselves as overturning out-dated interpretations of the bible, transforming hierarchical religious institutions, and re-orientating Christianity to step outside the walls of church buildings toward working among and serving others in the “real world.”

Drawing on ethnographic observations from emerging congregations, pub churches, neo-monastic communities, conferences, online networks, in-depth interviews, and congregational surveys in the US, UK, and Ireland, this book provides a comprehensive social scientific analysis of the development and significance of the ECM. Emerging Christians are shaping a distinct religious orientation that encourages individualism, deep relationships with others, new ideas around the nature of truth, doubt, and God, and innovations in preaching, worship, Eucharist, and leadership.

Activism and Restraint within the UK Supreme Court

This article provides evidence for the extent to which the UK Supreme Court as a body - and Supreme Court Justices as individuals - have displayed an activist or restrained attitude to their decision-making role. Taking October 2009 as the starting point (when the UKSC came into existence) the article surveys the degree to which the Court and individual Justices have (1) departed from precedents, (2) interpreted legislation in unanticipated ways, (3) rejected the government's position on matters of social, economic or foreign policy, and (4) developed the common law. The article concludes that, while the Supreme Court as a whole remains as conservative as the Appellate Committee of the House of Lords which preceded it (with the possible exception of its approach to immigration law), there are notable differences between the attitudes of individual Justices, one or two of whom appear to be straining at the leash.