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Rationale: The optimal strategy for the diagnosis of latent tuberculosis infection is controversial. Adoption of a two-step strategy (tuberculin skin test [TST] followed by an IFN-gamma release assay [IGRA], compared with an IGRA alone), may be limited by TST-mediated boosting of subsequent IGRA responses. Assessment of within-subject IGRA variability will aid in establishing thresholds for conversions and reversions, and interpretation of serial testing results.Objectives: To determine short-term IGRA variability and the impact of TST on subsequent IGRA results.Methods: Within-subject variability and TST-mediated boosting of IGRA responses were evaluated in 26 South African participants with varying exposure risk. IGRAs (T-SPOT.TB, QuantiFERON-TB Gold In-Tube [QuantiFERON-TB-GIT], PPD, and heparin-binding hemagglutinin) were repeated four times over 21 days pre-TST, and on Days 3, 7, 28, and 84 post-TST administration.Measurements and Main Results: All participants showed within-subject IGRA variability. Changes of +/-3 spots (T-SPOT.TB) or +/-80% from the mean IFN-gamma response (QuantiFERON-TB-GIT) over 3 weeks explained 95% of the variability. Spontaneous conversions/reversions occurred in 7 of 26 subjects (27%) (6 for T-SPOT.TB and 1 for QuantiFERON-TB-GIT [P = 0.049]) during the within-patient variability studies (pre-TST). After the TST eight subjects (33%) boosted above the defined baseline variability. By Day 7 post-TST, but not Day 3, 2 (12.5%) initially IGRA-negative test subjects converted. By contrast, boosting of PPD and heparin-binding hemagglutinin occurred by Day 3 post-TST.Conclusions: When using a two-step screening strategy it appears safe to perform a QuantiFERON-TB-GIT or T-SPOT.TB IGRA within 3 days of performing the TST. A 3-spot or 80% IFN-gamma response variation, on either side of baseline values, explains 95% of the short-term variability and may be useful for interpreting conversions and reversions, and values close to the cut-point. [ABSTRACT FROM AUTHOR]

(1) Populations of buried viable seeds of Acacia cyclops and A. saligna, invasive aliens of fynbos, were estimated to assess the effects on them of different shrub-clearing treatments, (2) Seed populations of both species declined significantly after 1 year with burning, but in general, not thereafter, (3) Seed banks of A. cyclops, but not of A. saligna, were reduced by shrub felling alone after 1 year, apparently because a high proportion of seeds do not have seed-coat induced dormancy, and thus germinate immediately, [ABSTRACT FROM AUTHOR]

Polymers consisting of more than one type of monomer, known as copolymers, are vital to both living and synthetic systems. Copolymerization has been studied theoretically in a number of contexts, often by considering a Markov process in which monomers are added or removed from the growing tip of a long copolymer. To date, the analysis of the most general models of this class has necessitated simulation. We present a general method for analyzing such processes without resorting to simulation. Our method can be applied to models with an arbitrary network of sub-steps prior to addition or removal of a monomer, including non-equilibrium kinetic proofreading cycles. Moreover, the approach allows for a dependency of addition and removal reactions on the neighboring site in the copolymer and thermodynamically self-consistent models in which all steps are assumed to be microscopically reversible. Using our approach, thermodynamic quantities such as chemical work; kinetic quantities such as time taken to grow; and statistical quantities such as the distribution of monomer types in the growing copolymer can be directly derived either analytically or numerically from the model definition.

The production of sequence-specific copolymers using copolymer templates is fundamental to the synthesis of complex biological molecules and is a promising framework for the synthesis of synthetic chemical complexes. Unlike the superficially similar process of self-assembly, however, the development of synthetic systems that implement templated copying of copolymers under constant environmental conditions has been challenging. The main difficulty has been overcoming product inhibition or the tendency of products to adhere strongly to their templates-an effect that gets exponentially stronger with the template length. We develop coarse-grained models of copolymerization on a finite-length template and analyze them through stochastic simulation. We use these models first to demonstrate that product inhibition prevents reliable template copying and then ask how this problem can be overcome to achieve cyclic production of polymer copies of the right length and sequence in an autonomous and chemically driven context. We find that a simple addition to the model is sufficient to generate far longer polymer products that initially form on, and then separate from, the template. In this approach, some of the free energy of polymerization is diverted into disrupting copy-template bonds behind the leading edge of the growing copy copolymer. By additionally weakening the final copy-template bond at the end of the template, the model predicts that reliable copying with a high yield of full-length, sequence-matched products is possible over large ranges of parameter space, opening the way to the engineering of synthetic copying systems that operate autonomously.

Substantial geographical differences exist for Hodgkin and other lymphoproliferative disorders with these having previously been documented in a report from the lymphoma reclassification project. In the light of rampant human immunodeficiency syndrome, largely centred in sub-Sahara, this experience is updated in a further 512 consecutive individuals treated over an 8-year period in a privately based academic centre. Median age was 55.2 years 61% were males, 10% had Hodgkin lymphoma and, overall, constitutional symptoms were present in 20%. Prior to referral 19% had received chemotherapy and a further 20% some form of irradiation. Median survival in hairy cell leukaemia (n=14), chronic lymphocytic leukaemia-small lymphocytic lymphoma (n=103), Hodgkin (n=41) and follicular lymphoma (n=59) was not reached at the time of analysis and exceeded 36 months. This was followed by 32 months for those with mantle cell (n=7), splenic (n=2) and extranodal marginal cell (n=11), 24 months for T-cell lymphomas (n=24), 20 months for diffuse large B-cell variants (n=88) but only 12 months for the aggressive tumours exemplified by Burkitt (n=7) and lymphoblastic subtypes (n=6). The remaining 36 patients had to be excluded because numbers were too small for statistical analysis or unreliable staging. Adverse factors were constitutional symptoms, prior treatment with chemotherapy, intermediate or high-risk scores as defined by the international prognostic index, histologic grading and certain anatomical sites of primary tumour. In contrast gender, staging by Rye or Rai classification, retroviral infection and prior treatment with radiotherapy were without effect. Overall survival at 3 years in each category was compared to the curve for the entire cohort and was 100% in hairy cell leukaemia receiving two chlorodeoxyadenosine and greater than 88% in Hodgkin lymphoma treated according to the German study group protocols (p=0.0004). Corresponding figures for chronic lymphocytic leukaemia-small lymphocytic lymphoma were 82% (p=0.0006), follicular lymphoma 71% (p=0.060), peripheral T-cell lymphoma 43% (p=0.0156), diffuse large B-cell lymphoma 39% (p<0.0001), aggressive tumours 25% (p=0.0002) and for the indolent categories including mantle cell, splenic and extra nodal marginal cell lymphomas 22% (p=0.2023). Outcome argues in favour of patient management by a multidisciplinary team implicit in which are standardised protocols for diagnosis, staging and treatment. Under these circumstances the well recognized centre effect applies when results approximate those from first world reference centres. Conversely any deviation from such a disciplined approach is unlikely to achieve comparable benefit and therefore to be strongly discouraged., ((c) 2010. Published by Elsevier Ltd.)

Background and Objectives: Immunohematopoietic stem cell transplantation has curative potential in selected hematologic disorders. Stem cell transplantation was introduced into South Africa in 1970 as a structured experimental and clinical program. In this report, we summarize the demography and outcome by disease category, gender, and type of procedure in patients older than 18 years of age who were seen from April 1995 to December 2002., Patients and Methods: This retrospective analysis included 247 individuals over 18 years of age for whom complete data were available. These patients received grafts mostly from peripheral blood with the appropriate stem cell population recovered by apheresis., Results: Patient ages ranged from 20 to 65 years with a median age of 42 years. There were 101 females and 146 males. There were no withdrawals and 63% survived to the end of the study. At 96 months of follow-up, a stable plateau was reached for each disease category. Median survival was 3.3 years (n=6, 14.6%) for acute lymphoblastic anemia, 3.1 years (n=44, 18%) for acute myeloid leukemia, 2.8 years (n=47, 19%) for chronic granulocytic leukemia, 2.8 years (n=71, 29%) for lymphoma, 1.5 years (n=23, 9%) for myeloma, 1.43 years (n=10, 4%) for aplasia, and 1.4 years (n=38, 15%) for a miscellaneous group comprising less than 10 examples each. Multivariate analysis showed that only diagnosis and age had a significant impact on survival, but these two variables might be interrelated. There was no significant difference in outcome by source of graft., Conclusion: The results confirm that procedures carried out in a properly constituted and dedicated unit, which meets established criteria and strictly observes treatment protocols, generate results comparable to those in a First World referral center. Low rates of transplant-related mortality, rejection and graft-versus-host disease are confirmed, but the benefits cannot be extrapolated outside of academically oriented and supervised facilities.

Unlabelled: INTRODUCTION AND STUDY DESIGN: We conducted a retrospective analysis of consecutive referrals of patients under 18 years of age undergoing immunohematopoietic stem cell transplantation to assess the influence of age, diagnosis, graft type and gender on survival. We also contrasted program activity and outcome to that reported from a state hospital in the same geographical area over a comparable period., Methods: Conditioning employed either a sequential combination of fractionated 12Gy whole body and 6Gy total nodal irradiation separated by 120mg/kg of cyclophosphamide in patients over 15 years of age. Alternatively, the latter agent was combined initially with oral busulphan and later the intravenous equivalent. Neuroblastoma cases were prepared using a different regimen. In allografts the harvested product underwent ex vivo T-cell depletion with the humanized version of anti-CD 52 monoclonal antibody designated Campath 1H. No additional immunosuppression was given except where matched unrelated volunteer donors were employed., Results: Sixty-eight procedures were carried out in 61 patients over a 6-year period. Of 11 with acute myeloid leukemia, 8 are alive and well whereas 8 of the 14 with the lymphoblastic variant have died. Of the remaining 12 with hematologic malignancy, all but 2 are alive. Ten of the 17 with aplasia are alive as are all with thalassemia or sickle cell disease. None of the four variables tested affected survival., Conclusion: Our analysis indicates that the standardized preparative regimen, coupled with a now well-established immunosuppressive regimen, is as effective in patients under 18 years of age as in adults. Our analysis also indicates that in a resource-scarce or developing country, it is mandatory to limit high-risk and relatively expensive procedures to active teams that enjoy international accreditation, whether these be in the state or private sector.

To document outcome in Hodgkin and other lymphomas from a privately based academic centre the clinical records from 253 consecutive referrals were analysed. Diagnosis was according to World Health Organization criteria, prognosis assigned by the international index and therapy risk-stratified with results subject to appropriate statistical methodology. None of these patients underwent transplantation. For the cohort the median age was 55 years (range 11-94) and 63% were male. Constitutional symptoms were present in 22%; a quarter had previous chemotherapy and a third some form of irradiation prior to referral. Fifty-seven percent were stage I or II and 21% had nodal disease above and below the diaphragm whilst in the remainder cells were present in the circulation and this included the subset of chronic lymphocytic leukaemia -- small lymphocytic lymphoma. Positron emission scanning was not available for these studies. Median survival for the cohort is 3.2 years and reduced to 1.3 years by the presence of unexplained fever, sweating or inappropriate weight loss. Further adverse factors included any prior treatment, intermediate or high-grade histopathology, risk factors defined by the International Prognostic Index as well as late Rai stages. Analysed by disease category Hodgkin lymphoma (n=17) when managed according to the German Study Group protocols and hairy cell leukaemia (n=10) treated with two chlorodeoxyadenosine -- both had a stable plateau in excess of 90%. The corresponding figures for follicular variants (n=31) was 72% in the low risk and 58% in the remainder when treated with cyclophosphamide, vincristine and prednisone. Curves for the aggressive or diffuse large B-cell lymphoma (n=44) fell initially to 48%, but relapse continued in stages III and IV to the current level of 18% when receiving cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone on the 21-day schedule. Chronic lymphocytic leukaemia -- small lymphocytic lymphoma (n=58) were initially given pulsed chlorambucil and sustained response was over 90% with low bulk, but declined to reach 30% as prognostic score rose. The miscellaneous categories (n<5 each) managed variably, but using the same criteria, were pooled and are presently at 62% and 30% for high and low grades. It is concluded that precise diagnosis, accurate staging and therapy on standardised risk-stratified programmes, delivered uniformly by a single multidisciplinary group, creates the all-important centre effect; matching figures are unlikely to apply outside these disciplined circumstances. The expectation from patients and referring physicians alike is that, since lymphomas are potentially curable, such an approach to comprehensive management will be regarded as standard even in an under resourced or Third World country. It follows that late referral and prior therapy will adversely affect performance status and compromise life span: These alternative approaches are inappropriate and strongly discouraged.

Three properties of interest in bioavailability studies using compartmental models are the area under the concentration curve, the maximum concentration, and the time to maximum concentration. Methods are described for finding designs that minimize the variance of the estimates of these quantities in such a model. These methods use prior information. Both prior estimates and prior distributions are used. The designs for an open one-compartment model are compared with the corresponding D theta-optimum design for all parameters and also with designs that minimize the sum of the scaled variances of the individual properties.

A survey was undertaken to determine the prevalence of use of androgenic anabolic steroids (AAS) by matric pupils in the western Cape. A cluster sample, stratified by language and a subjective assessment of sporting status, of 13 schools in the area was selected, and 1,361 pupils completed a questionnaire containing questions about sports participation and the use of AAS. The prevalence of use of AAS in the sample was 5.9/1,000 and prevalences in subgroups were 11.7/1,000 for males, 12.5/1,000 for male sports participants and 25.4/1,000 for Afrikaans-speaking male sports participants. A significant amount of under-reporting (AAS users denying their status as such) occurred. General knowledge about AAS was poor, particularly among females and non-sports participants. AAS users experienced more pressure to perform well at sport than did non-users; the drugs were obtained mostly from peers and no user indicated that they were legally obtained. Because there is much evidence regarding the detrimental effects of AAS on health, it is clear that a strategy must be adopted to decrease the prevalence of their use in the schoolgoing population.

Statistical analysis of specific IgE immune responses to a panel of nine allergens from 2,094 patients demonstrated significant clustering between Aspergillus fumigatus, Alternaria alternata, and Cladosporium herbarum, not explained by crossreactive elements. This may represent a linked, high responder status to these fungal antigens in the allergic population.

The outcome of the behavioural screening of 10- and 13-year-old pupils in selected schools in the Cape Peninsula is reported and the implications discussed. According to parents' reports 21% of 10-year-old and 17.6% of 13-year-old children met the criteria for behaviour disorder. The rates according to teachers' reports were 9.5% and 10.5% respectively. Behaviour disorder occurred with significantly greater frequency among boys, pupils older than the expected age for their standard, pupils with an intelligence quotient below 100, and pupils who had a learning disability.

The accuracy and precision of cholesterol assay in the western Cape region is reported. The survey was carried out over 15 weeks utilising three human EDTA plasma pools with normal, borderline high and high cholesterol levels respectively. All 11 laboratories in the region providing a service to academic, provincial or military hospitals or to the private medical sector were included in the study. Ten of the 11 laboratories utilised automated enzymatic methods of cholesterol assay whereas 1 used a manual procedure based on the Liebermann-Burchard reaction. Methods were standardised by means of a variety of commercial calibrator material in all except 1 laboratory which used reference sera from the Centers for Disease Control, Atlanta. The performance of the 4 best laboratories met the standard of precision recommended for cholesterol assay, viz. total coefficient of variation of less than or equal to 2.5%. However, only 2 of the 11 laboratories achieved the optimum objective of an overall bias of less than 2.0% together with precision of less than or equal to 2.5%. Rational use of cholesterol assay for diagnosis and management will therefore require standardisation of cholesterol assay on a common reference material and greater attention to analytical factors influencing the reproducibility of results. Intrinsic biological variation also contributes uncertainty to the interpretation of a single value. Thus important clinical decisions must be based on two or more assays carried out using appropriate methodology.