A High-Density Genome-Wide Association Screen of Sporadic ALS in US Veterans

Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U.S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We tested ∼1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4×10−4) and rs6985069 near ELP3 (p = 4.8×10−4). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder

Contemplating the approach of RAU's founders towards radically transforming Afrikaans speaker identity in taking economic responsibility

This discussion on the former Rand Afrikaans University (RAU) covers the founding years of the University from 1955 to 1975. What should become clear from the contemplations is that the establishment of RAU in 1968 (today the University of Johannesburg), was not driven by the increase in the population of white Afrikaans speakers on the Witwatersrand or to act as a force against the liberal influences of the University of the Witwatersrand (Wits). The philosophy behind the establishment of RAU was mainly to reposition and empower white Afrikaans speakers with the education required to ensure that they could take their place in particularly the Witwatersrand as economic heartland of South Africa, and South Africa in general. Part of this approach by the founders was to create and develop RAU to become the most modern Afrikaans university of its time, providing quality teaching and learning of a high local and international standards. The prominence of being a university driven by specific ideals contributed to the forming of the Afrikaans speaker’s identity in education and the national economy. As examples, this discussion mainly emphasises some new teaching methods introduced at the time, visibly blending with a refreshed view on the architectural design to accommodate the philosophical ideals envisioned for RAU. The founders’ vision was for RAU to become an educational instrument towards transforming white Afrikaans speaker identity within a modernised context

Buisfontein: \'n pionierserfenis as toerisme-bestemming

Buisfontein – a pioneer heritage as tourist attraction: Buisfontein, situated close to the present-day Klerksdorp, is a farm that is not unfamiliar to the cultural experts of South Africa. Though inhabitants and migrations of nomad groups – centuries ago – can certainly be exposed to more research to expand the socio-anthropological value of the area's future focus on tourism, the remains certainly already reflect a unique past. The historically well-known and contentious Coenraad de Buys/Buis is associated with this environment, followed by some of the first white Trekkers who settled in the area. Within this framework a space has been developed for the P.F. Ernst descendants – known with the farm for decades as owners and inhabitants – to re-purchase portions of Buisfontein from the new owners and to restore some of the dwellings, as originally occupied, for the Ernst descendants, for regional-cultural enthusiasts and other interested parties. Some distinguishing features of the environment (the fountains, ridges and trees), the game that formerly featured in this area, the remains of groups that occupied the region for long periods before the Trekkers settled in the area after 1838, are facets that will also be accentuated in a tourism focus for the future. Probably the most distinctive feature of the restoration effort by the Ernst family is the fact that it is undertaken exclusively with private funds. In the present article the focus will be on aspects of the rich pioneering history that allows Buisfontein to become a beacon in the tourism market in its own right. The features of the environment are also accentuated as far as they were prominent in human usage. The conclusion will shed some light on Buisfontein as a tourist attraction for the future. Keywords: Buisfontein; PF Ernst; HJ van der Merwe; Coenraad de Buys/Buis; Klerksdorp; Hartebeestfontein; tourism; historical buildings; fountains/eyes; architectureSouth Africa Journal of Cultural History Vol. 22 (1) 2008: pp. 56-8

'n Omgewingsgeskiedenis van Suid-Afrika

Lettere En WysbegeerteGeografie En OmgewingstudiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Pilot study of probe-based confocal laser endomicroscopy during colonoscopic surveillance of patients with longstanding ulcerative colitis

Background and aims: Surveillance of patients with ulcerative colitis consists of taking targeted and random biopsies, which is time-consuming and of doubtful efficiency. The use of probe-based confocal laser endomicroscopy (pCLE) may increase efficiency. This prospective pilot study aimed to evaluate the feasibility and diagnostic accuracy of pCLE in ulcerative colitis surveillance. Methods: In 22 patients with ulcerative colitis, 48 visible lesions and 87 random areas were initially evaluated by real-time narrow-band imaging (NBI) and high-definition endoscopy (HDE). Before taking biopsies, fluorescein-enhanced pCLE was performed. All pCLE videoswere scored afterwards by two endoscopists who were blinded to histology and endoscopy. Outcome measures were: (1) the feasibility of pCLE, expressed as pCLE imaging time required, percentage of imaging time with clear pCLE histology, and pCLE video quality as rated by two endoscopists; and (2) the diagnostic accuracy of pCLE. Results: The median pCLE imaging time required was 98 seconds for lesions vs. 66 seconds for random areas (P = 0.002). The median percentages of imaging time with clear pCLE histology were 61% vs. 81% respectively (P <0.001). The pCLE video quality was rated as good/excellent in 69%. Feasibility was significantly poorer for sessile and pedunculated mobile lesions. The sensitivity, specificity, and accuracy of blinded pCLE were 65%, 82%, and 81%, whereas these figures were 100%, 89%, and 92% for real-time endoscopic diagnosis with NBI and HDE. Conclusion: This study demonstrates that pCLE for ulcerative colitis surveillance is feasible with reasonable diagnostic accuracy. Future research should show whether increased experience with pCLE improves its ease of use and whether real-time pCLE diagnosis is associated with greater diagnostic accurac