Should baseline PSA testing be performed in men aged 40 to detect those aged 50 or less who are at risk of aggressive prostate cancer?

The original publication is available at http://www.samj.org.zaWe aimed to evaluate the presenting features and treatment outcome of prostate cancer in men aged <50 years, in a region where prostate specific antigen (PSA) screening is not readily available and most men present with symptoms. Methods. We analysed the data of 1 571 men with prostatic adenocarcinoma treated between January 1997 and December 2008 at our institution, a tertiary level public sector hospital serving a largely indigent population. Statistical analysis was performed using Student’s, the Mann-Whitney and Fisher’s exact tests where appropriate (p<0.05 accepted as statistically significant). Results. Of 1 571 men, 47 (3%) were aged <50 years. The group aged 50 years, had a significantly greater proportion with poorly differentiated adenocarcinoma (53%), locally advanced (stage T3 - 4) tumours (56%), haematogenous metastases (75%), significantly higher serum PSA at diagnosis (mean 621, median 74 ng/ml) and shorter survival. Conclusions. Men aged <50 years presenting with symptoms owing to prostate cancer had significantly higher-risk disease, higher mean PSA, and poorer prognosis than men aged >50 years. To diagnose prostate cancer at a potentially curable stage in men aged <50 years, it is necessary to initiate baseline PSA testing at age 40 and 45 years, and to select high-risk men for PSA surveillance in order to diagnose potentially curable cancer in those with a life expectancy >20 - 25 years.Publishers' Versio

Developing a Patient-Specific Maxillary Implant Using Additive Manufacturing and Design

Published Conference ProceedingsMaxillectomy is the surgical removal or resection of the maxilla or upper jaw bone. A total or partial maxillectomy can be performed depending on how far the tumour has spread. This paper will discuss a patient diagnosed with an aggressive tumour in half of the top jaw who had to undergo an operation to remove the hemi-maxilla and orbital floor. Due to the extent and complexity of the defect, it was decided to manufacture an anatomical model of the hard tissues for planning a possible laser-sintered titanium implant using Additive Manufacturing (AM). The CRPM had only two weeks to design and manufacture the titanium implant, due to the severity of the tumour. The anatomical model was sent to the surgeon to cut the nylon model where the bone resection was planned. Furthermore, the prosthodontist made a wax model of the planned titanium frame that was reverse- engineered and used as reference geometry in the design software.Materialise® design suite was used to design the patient-specific maxilla and cutting jig. The EOS M280 Direct Metal Laser Sintering (DMLS) system was instrumental in achieving the direct manufacturing of the bio-compatible titanium implant. The EOS P385 system was used to manufacture the pre-operation planning model as well as the cutting jig.The process chain followed to complete this case study will be discussed showing how this intervention improved the quality of life of a SA patient. Furthermore, the proposed paper and presentation will discuss the post-operation review of the patient showing the impact AM had in accelerating patient-specific implant manufacturing. The authors seek to claim a progressed level of maturity in the proposed manufacturing value chain. The claim is based on the successful completion of the analysis and synthesis of the problem , the validated proof-of-concept of the manufacturing process and the in-vivo implementation of the final product

Should baseline PSA testing be performed in men aged 40 to detect those aged 50 or less who are at risk of aggressive prostate cancer?

Objective. We aimed to evaluate the presenting features and treatment outcome of prostate cancer in men age

Drivers of inter-annual variability in Net Ecosystem Exchange in a semi-arid savanna ecosystem, South Africa

Inter-annual variability in primary production and ecosystem respiration was explored using eddy-covariance data at a semi-arid savanna site in the Kruger Park, South Africa. New methods of extrapolating night-time respiration to the entire day and filling gaps in eddy-covariance data in semi-arid systems were developed. Net ecosystem exchange (NEE) in these systems occurs as pulses associated with rainfall events, a pattern not well-represented in current standard gap-filling procedures developed primarily for temperate flux sites. They furthermore do not take into account the decrease in respiration at high soil temperatures. An artificial neural network (ANN) model incorporating these features predicted measured fluxes accurately (MAE 0.42 gC/m&lt;sup&gt;2&lt;/sup&gt;/day), and was able to represent the seasonal patterns of photosynthesis and respiration at the site. The amount of green leaf area (indexed using satellite-derived estimates of fractional interception of photosynthetically active radiation &lt;i&gt;f&lt;/i&gt;&lt;sub&gt;APAR&lt;/sub&gt;), and the timing and magnitude of rainfall events, were the two most important predictors used in the ANN model. These drivers were also identified by multiple linear regressions (MLR), with strong interactive effects. The annual integral of the filled NEE data was found to range from &amp;minus;138 to +155 g C/m&lt;sup&gt;2&lt;/sup&gt;/y over the 5 year eddy covariance measurement period. When applied to a 25 year time series of meteorological data, the ANN model predicts an annual mean NEE of 75(&amp;plusmn;105) g C/m&lt;sup&gt;2&lt;/sup&gt;/y. The main correlates of this inter-annual variability were found to be variation in the amount of absorbed photosynthetically active radiation (APAR), length of the growing season, and number of days in the year when moisture was available in the soil

A simulation study to compare reference and other priors in the case of a standard univariate Student t-distribution

In this paper, reference and probability-matching priors are derived for the univariate Student t-distribution. These priors generally lead to procedures with properties frequentists can relate to while still retaining Bayes validity. The priors are tested by performing simulation studies. The focus is on the relative mean squared error from the posterior median and on the frequentist coverage of the 95% credibility intervals for a sample of size n = 30. Average interval lengths of the credibility intervals as well as the modes of the interval lengths based on 2 000 simulations are also considered. The performance of the priors is also tested on real data, namely daily logarithmic returns of IBM stocks

Progressive familial heart block type I : clinical and pathological observations

CITATION: 1991: .Van der Merwe, P.-L. et al. 1991. Progressive familial heart block type I : clinical and pathological observations. South African Medical Journal, 80:34-38.The original publication is available at http://www.samj.org.zaProgressive familial heart block type I (PFHB-I) is an autosomal inherited disease. It was previously postulated that the disease is limited to the cardiac conduction tissue. The presentation of a patient with dilated cardiomyopathy focused on the possibility that this might be part of PFHB-I. This observation led to routine echocardiographic examination of patients with complete heart block, who belonged to PFHB-I families, and another 5 cases with signs of dilated cardiomyopathy were identified. This is the first time, to our knowledge, that the histological picture of PFHB-I has been described. From these case reports it is clear that in the presence of a dilated cardiomyopathy the prognosis in PFHB-I tends to be poor.Publisher’s versio

Long-term follow-up of R403W MYH7 and R92W TNNT2 HCM families : mutations determine left ventricular dimensions but not wall thickness during disease progression

The original publication is available at http://www.cvja.co.za/CVJA holds the copyrightThe clinical profile and prognosis of patients with hypertrophic cardiomyopathy, a primary cardiac muscle disease caused mostly by mutations in sarcomeric protein-encoding genes, have been linked to particular disease-causing mutations in the past. However, such associations are often based on cross-sectional observations, as longitudinal studies of the progression of the disease in genotypically defined patients are sparse. Most importantly, the relative contribution of age, gender and genetic cause to disease profile and progression has not yet been reported, and the question remains whether one or more of these factors could mask the effect of the other(s). Methods: We previously described cross-sectional family studies of two hypertrophic cardiomyopathy (HCM)-causing mutations, R92WTNNT2 and R403WMYH7, both associated with minimal hypertrophy, but with widely different life expectancies. We re-investigated 22 and 26 R92WTNNT2 and R403WMYH7 mutation carriers in these and additional South African R92WTNNT2 families after a mean 11.08 ± 2.79 years, and compared the influence of the two mutations, in the context of age and gender, on disease progression. Results: We demonstrated a positive correlation between age and interventricular septal thickness for both mutations, with more than a third of all mutation carriers developing clinically recognised hypertrophy only after the age of 35 years. This period of hypertrophically silent HCM also coincided with the years in which most sudden cardiac deaths occurred, particularly in male R92WTNNT2 carriers. Statistical analyses indicated that the particular mutation was the strongest determinant of left ventricular remodelling; particularly, LVESD increased and EF reduction was noted in the majority of R403WMYH7 carriers, which may require clinical follow-up over the longer term. Conclusions: Statistical modelling of follow-up data suggests that an interplay between unidentified, possibly genderassociated factors, and the causal mutation are the determinants of eventual cardiac function and survival, but not of the extent of hypertrophy, and emphasises the need for long-term follow-up even in individuals with apparently mild disease.Publishers' Versio

Scaling of Heteroepitaxial Island Sizes

Monte Carlo simulations of an atomistic solid-on-solid model are used to study the effect of lattice misfit on the distribution of two-dimensional islands sizes as a function of coverage $\Theta$ in the submonolayer aggregation regime of epitaxial growth. Misfit promotes the detachment of atoms from the perimeter of large pseudomorphic islands and thus favors their dissolution into smaller islands that relieve strain more efficiently. The number density of islands composed of $s$ atoms exhibits scaling in the form \mbox{$N_s(\Theta) \sim \Theta / \langle s \rangle^2 \, g(s/\langle s \rangle$)} where $\langle s \rangle$ is the average island size. Unlike the case of homoepitaxy, a rate equation theory based on this observation leads to qualitatively different behavior than observed in the simulations.Comment: 10 pages, LaTeX 2.09, IC-DDV-94-00

Genetic variation in angiotensin II type 2 receptor gene influences extent of left ventricular hypertrophy in hypertrophic cardiomyopathy independent of blood pressure

Introduction. Hypertrophic cardiomyopathy (HCM), an inherited primary cardiac disorder mostly caused by defective sarcomeric proteins, serves as a model to investigate left ventricular hypertrophy (LVH). HCM manifests extreme variability in the degree and distribution of LVH, even in patients with the same causal mutation. Genes coding for renin—angiotensin—aldosterone system components have been studied as hypertrophy modifiers in HCM, with emphasis on the angiotensin (Ang) II type 1 receptor (AT1R). However, Ang II binding to Ang II type 2 receptors (AT2R) also has hypertrophy-modulating effects. Methods. We investigated the effect of the functional +1675 G/A polymorphism (rs1403543) and additional single nucleotide polymorphisms in the 3' untranslated region of the AT2R gene ( AGTR2) on a heritable composite hypertrophy score in an HCM family cohort in which HCM founder mutations segregate. Results. We find significant association between rs1403543 and hypertrophy, with each A allele decreasing the average wall thickness by ~0.5 mm, independent of the effects of the primary HCM causal mutation, blood pressure and other hypertrophy covariates ( p = 0.020). Conclusion. This study therefore confirms a hypertrophy-modulating effect for AT2R also in HCM and implies that +1675 G/A could potentially be used in a panel of markers that profile a genetic predisposition to LVH in HCM