A Longitudinal Study of Stargardt Disease: Clinical and Electrophysiologic Assessment, Progression, and Genotype Correlations

Purpose: To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype. Design: Cohort study of 59 patients. Methods: Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3 ms for the 30 Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken. Results: The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients. Conclusions: All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions. © 2013 Elsevier Inc. All rights reserved.

A qualitative study of psychological, social and behavioral barriers to appropriate food portion size control

Background: Given the worldwide prevalence of overweight and obesity, there is a clear need for meaningful practical healthy eating advice - not only in relation to food choice, but also on appropriate food portion sizes. As the majority of portion size research to date has been overwhelmingly quantitative in design, there is a clear need to qualitatively explore consumers’ views in order to fully understand how food portion size decisions are made. Using qualitative methodology this present study aimed to explore consumers’ views about factors influencing their portion size selection and consumption and to identify barriers to appropriate portion size control.

Methods: Ten focus groups with four to nine participants in each were formed with a total of 66 persons (aged 19–64 years) living on the island of Ireland. The semi-structured discussions elicited participants’ perceptions of suggested serving size guidance and explored the influence of personal, social and environmental factors on their food portion size consumption. Audiotapes of the discussions were professionally transcribed verbatim, loaded into NVivo 9, and analysed using an inductive thematic analysis procedure.
Results: The rich descriptive data derived from participants highlight that unhealthy portion size behaviors emanate from various psychological, social and behavioral factors. These bypass reflective and deliberative control, and converge to constitute significant barriers to healthy portion size control. Seven significant barriers to healthy portion size control were apparent: (1) lack of clarity and irrelevance of suggested serving size guidance; (2) guiltless eating; (3) lack of self-control over food cues; (4) distracted eating; (5) social pressures; (6) emotional eating rewards;
and (7) quantification habits ingrained from childhood.

Conclusions: Portion size control strategies should empower consumers to overcome these effects so that the consumption of appropriate food portion sizes becomes automatic and habitual.
Keywords: Food portion size, Barriers, Obesity, Consumers, Qualitative study. © 2013 Spence et al.; licensee BioMed Central Ltd

A Review of Meditation in the Irish Construction Industry: Critical Success Factors in Competencies and Processes

The construction industry notoriously excels at dispute creation – both in Ireland and world wide. This paper exams mediation in the Irish construction industry based around critical success factors in the competencies and processes required by mediators operating in the construction industry. Through conducting the relevant analysis, it was possible to extract and outline the resulting critical success factors in process and competencies of mediators in the Irish construction industry. This was achieved through a review of the literature, followed by detailed interviews from industry experts to elicit and highlight the core competencies required. To aid in the study, qualitative analysis using mind mapping software was adopted, thus assisting the identification of the key factors. Following analysis, facilitative mediation was identified as best suited for the industry in question; recommendations and experience were key for mediator selection and five and six factors were identified for mediator skills and mediation critical success factors respectively. The results returned are similar to those determined by authors in other countries and provide a good reference point for the development the industry. By following the findings of this report mediators and parties in dispute can improve processes and be more successful in outcomes. In this study the author shows that mediation is an effective and appropriate method of resolving disputes within the Irish construction industry.

The Opportunistic Pathogen Propionibacterium acnes: Insights into Typing, Human Disease, Clonal Diversification and CAMP Factor Evolution

We previously described a Multilocus Sequence Typing (MLST) scheme based on eight genes that facilitates population genetic and evolutionary analysis of P. acnes. While MLST is a portable method for unambiguous typing of bacteria, it is expensive and labour intensive. Against this background, we now describe a refined version of this scheme based on two housekeeping (aroE; guaA) and two putative virulence (tly; camp2) genes (MLST) that correctly predicted the phylogroup (IA, IA, IB, IC, II, III), clonal complex (CC) and sequence type (ST) (novel or described) status for 91% isolates (n = 372) via cross-referencing of the four gene allelic profiles to the full eight gene versions available in the MLST database (http://pubmlst.org/pacnes/). Even in the small number of cases where specific STs were not completely resolved, the MLST method still correctly determined phylogroup and CC membership. Examination of nucleotide changes within all the MLST loci provides evidence that point mutations generate new alleles approximately 1.5 times as frequently as recombination; although the latter still plays an important role in the bacterium's evolution. The secreted/cell-associated 'virulence' factors tly and camp2 show no clear evidence of episodic or pervasive positive selection and have diversified at a rate similar to housekeeping loci. The co-evolution of these genes with the core genome might also indicate a role in commensal/normal existence constraining their diversity and preventing their loss from the P. acnes population. The possibility that members of the expanded CAMP factor protein family, including camp2, may have been lost from other propionibacteria, but not P. acnes, would further argue for a possible role in niche/host adaption leading to their retention within the genome. These evolutionary insights may prove important for discussions surrounding camp2 as an immunotherapy target for acne, and the effect such treatments may have on commensal lineages. © 2013 McDowell et al.

Adaptive uncertain information fusion to enhance plan selection in BDI agent systems

Correctly modelling and reasoning with uncertain information from heterogeneous sources in large-scale systems is critical when the reliability is unknown and we still want to derive adequate conclusions. To this end, context-dependent merging strategies have been proposed in the literature. In this paper we investigate how one such context-dependent merging strategy (originally defined for possibility theory), called largely partially maximal consistent subsets (LPMCS), can be adapted to Dempster-Shafer (DS) theory. We identify those measures for the degree of uncertainty and internal conflict that are available in DS theory and show how they can be used for guiding LPMCS merging. A simplified real-world power distribution scenario illustrates our framework. We also briefly discuss how our approach can be incorporated into a multi-agent programming language, thus leading to better plan selection and decision making.

Effect of Impeller Design on Homogeneity, Size and Strength of Pharmaceutical Granules produced by High Shear Wet Granulation

Small mixer impeller design is not tailored for granulation because impellers are intended for a wide range of processes. The aim of this research was to evaluate the performances of several impellers to provide guidance on the selection and design for the purposes of granulation. Lactose granules were produced using wet granulation with water as a binder. A Kenwood KM070 mixer was used as a standard apparatus and five impeller designs with different shapes and surface areas were used. The efficacy of granulate formation was measured by adding an optically sensitive tracer to determine variations in active ingredient content across random samples of granules from the same size classes. It was found that impeller design influenced the homogeneity of the granules and therefore can affect final product performance. The variation in active ingredient content across granules of differing size was also investigated. The results show that small granules were more potent than larger granules.

Chapter Three – Host–Parasite Interactions and the Evolution of Immune Defense

Parasites and pathogens are ubiquitous and act as an important selection pressure on animals. Here, drawing primarily on our own research, mostly on insects, we illustrate how host-parasite interactions have played a role in the evolution of a range of phenomena, including animal coloration, social behavior, foraging ecology, sexual selection, and life-history tradeoffs, as well as how variation in host behavior and ecology can drive variation in parasitism risk and host allocation of resources to immunity and other antiparasite defenses. We conclude by identifying key areas for future study.

Robust bimodal person identification using face and speech with limited training data and corruption of both modalities

This paper presents a novel method of audio-visual fusion for person identification where both the speech and facial modalities may be corrupted, and there is a lack of prior knowledge about the corruption. Furthermore, we assume there is a limited amount of training data for each modality (e.g., a short training speech segment and a single training facial image for each person). A new representation and a modified cosine similarity are introduced for combining and comparing bimodal features with limited training data as well as vastly differing data rates and feature sizes. Optimal feature selection and multicondition training are used to reduce the mismatch between training and testing, thereby making the system robust to unknown bimodal corruption. Experiments have been carried out on a bimodal data set created from the SPIDRE and AR databases with variable noise corruption of speech and occlusion in the face images. The new method has demonstrated improved recognition accuracy.

Genomics and the impact of new technologies on the management of colorectal cancer

High-throughput genomic technologies have the potential to have a major impact on preclinical and clinical drug development and the selection and stratification of patients in clinical trials. These technologies, which are at varying stages of commercialization, include array-based comparative genomic hybridization, single-nucleotide polymorphism arrays, and (the most mature example) expression-based arrays. One of the rate-limiting steps in the routine clinical application of expression array-based technology is the need for suitable clinical samples. One of the major challenges moving forward, therefore, relates to the ability to use formalin-fixed, paraffin-embedded--derived tissue in expression profiling-based approaches.

Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

Judicial Impartiality and Independence in Divided Societies: An Empirical Analysis of the Constitutional Court of Bosnia-Herzegovina

The role of Constitutional Courts in deeply divided societies is complicated by the danger that the salient societal cleavages may influence judicial decision-making and, consequently, undermine judicial independence and impartiality. With reference to the decisions of the Constitutional Court of Bosnia-Herzegovina, this article investigates the influence of ethno-nationalism on judicial behaviour and the extent to which variation in judicial tenure amplifies or dampens that influence. Based on a statistical analysis of an original dataset of the Court’s decisions, we find that the judges do in fact divide predictably along ethno-national lines, at least in certain types of cases, and that these divisions cannot be reduced to a residual loyalty to their appointing political parties. Contrary to some theoretical expectations, however, we find that long-term tenure does little to dampen the influence of ethno-nationalism on judicial behaviour. Moreover, our findings suggest that the longer a judge serves on the Court the more ethno-national affiliation seems to influence her decision-making. We conclude by considering how alternative arrangements for the selection and tenure of judges might help to ameliorate this problem.

Surface plasmon resonance biosensing: Approaches for screening and characterising antibodies for food diagnostics

Research in biosensing approaches as alternative techniques for food diagnostics for the detection of chemical contaminants and foodborne pathogens has increased over the last twenty years. The key component of such tests is the biorecognition element whereby polyclonal or monoclonal antibodies still dominate the market. Traditionally the screening of sera or cell culture media for the selection of polyclonal or monoclonal candidate antibodies respectively has been performed by enzyme immunoassays. For niche toxin compounds, enzyme immunoassays can be expensive and/or prohibitive methodologies for antibody production due to limitations in toxin supply for conjugate production. Automated, self-regenerating, chip-based biosensors proven in food diagnostics may be utilised as rapid screening tools for antibody candidate selection. This work describes the use of both single channel and multi-channel surface plasmon resonance (SPR) biosensors for the selection and characterisation of antibodies, and their evaluation in shellfish tissue as standard techniques for the detection of domoic acid, as a model toxin compound. The key advantages in the use of these biosensor techniques for screening hybridomas in monoclonal antibody production were the real time observation of molecular interaction and rapid turnaround time in analysis compared to enzyme immunoassays. The multichannel prototype instrument was superior with 96 analyses completed in 2h compared to 12h for the single channel and over 24h for the ELISA immunoassay. Antibodies of high sensitivity, IC50's ranging from 4.8 to 6.9ng/mL for monoclonal and 2.3-6.0ng/mL for polyclonal, for the detection of domoic acid in a 1min analysis time were selected. Although there is a progression for biosensor technology towards low cost, multiplexed portable diagnostics for the food industry, there remains a place for laboratory-based SPR instrumentation for antibody development for food diagnostics as shown herein.

Multi-Device Selection Scheduling in Non-Identically Distributed Fading Channels

Multiuser selection scheduling concept has been recently proposed in the literature in order to increase the multiuser diversity gain and overcome the significant feedback requirements for the opportunistic scheduling schemes. The main idea is that reducing the feedback overhead saves per-user power that could potentially be added for the data transmission. In this work, the authors propose to integrate the principle of multiuser selection and the proportional fair scheduling scheme. This is aimed especially at power-limited, multi-device systems in non-identically distributed fading channels. For the performance analysis, they derive closed-form expressions for the outage probabilities and the average system rate of the delay-sensitive and the delay-tolerant systems, respectively, and compare them with the full feedback multiuser diversity schemes. The discrete rate region is analytically presented, where the maximum average system rate can be obtained by properly choosing the number of partial devices. They optimise jointly the number of partial devices and the per-device power saving in order to maximise the average system rate under the power requirement. Through the authors’ results, they finally demonstrate that the proposed scheme leveraging the saved feedback power to add for the data transmission can outperform the full feedback multiuser diversity, in non-identical Rayleigh fading of devices’ channels.

Human capital and the quantity–quality trade-off during the demographic transition

This paper provides an empirical test of the child quantity–quality (QQ) trade-off predicted by unified growth theory. Using individual census returns from the 1911 Irish census, we examine whether children who attended school were from smaller families—as predicted by a standard QQ model. To measure causal effects, we use a selection of models robust to endogeneity concerns which we validate for this application using an Empirical Monte Carlo analysis. Our results show that a child remaining in school between the ages of 14 and 16 caused up to a 27 % reduction in fertility. Our results are robust to alternative estimation techniques with different modeling assumptions, sample selection, and alternative definitions of fertility. These findings highlight the importance of the demographic transition as a mechanism which underpinned the expansion in human capital witnessed in Western economies during the twentieth century.