Initial burden of disease estimates for South Africa, 2000

BACKGROUND This paper describes the first national burden of disease study for South Africa. The main focus is the burden due to premature mortality, i.e. years of life lost (YLLs). In addition, estimates of the burden contributed by morbidity, i.e. the years lived with disability (YLDs), are obtained to calculate disability-adjusted life years (DALYs); and the impact of AIDS on premature mortality in the year 2010 is assessed. METHOD Owing to the rapid mortality transition and the lack of timely data, a modelling approach has been adopted. The total mortality for the year 2000 is estimated using a demographic and AIDS model. The non-AIDS cause-of-death profile is estimated using three sources of data: Statistics South Africa, the National Department of Home Affairs, and the National Injury Mortality Surveillance System. A ratio method is used to estimate the YLDs from the YLL estimates. RESULTS The top single cause of mortality burden was HIV/AIDS followed by homicide, tuberculosis, road traffic accidents and diarrhoea. HIV/AIDS accounted for 38% of total YLLs, which is proportionately higher for females (47%) than for males (33%). Pre-transitional diseases, usually associated with poverty and underdevelopment, accounted for 25%, non-communicable diseases 21% and injuries 16% of YLLs. The DALY estimates highlight the fact that mortality alone underestimates the burden of disease, especially with regard to unintentional injuries, respiratory disease, and nervous system, mental and sense organ disorders. The impact of HIV/AIDS is expected to more than double the burden of premature mortality by the year 2010. CONCLUSION This study has drawn together data from a range of sources to develop coherent estimates of premature mortality by cause. South Africa is experiencing a quadruple burden of disease comprising the pre-transitional diseases, the emerging chronic diseases, injuries, and HIV/AIDS. Unless interventions that reduce morbidity and delay morbidity become widely available, the burden due to HIV/AIDS can be expected to grow very rapidly in the next few years. An improved base of information is needed to assess the morbidity impact more accurately.

Provincial mortality in South Africa, 2000 - priority-setting for now and a benchmark for the future

Background. Cause-of-death statistics are an essential component of health information. Despite improvements, underregistration and misclassification of causes make it difficult to interpret the official death statistics. Objective. To estimate consistent cause-specific death rates for the year 2000 and to identify the leading causes of death and premature mortality in the provinces. Methods. Total number of deaths and population size were estimated using the Actuarial Society of South Africa ASSA2000 AIDS and demographic model. Cause-of-death profiles based on Statistics South Africa's 15% sample, adjusted for misclassification of deaths due to ill-defined causes and AIDS deaths due to indicator conditions, were applied to the total deaths by age and sex. Age-standardised rates and years of life lost were calculated using age weighting and discounting. Results. Life expectancy in KwaZulu-Natal and Mpumalanga is about 10 years lower than that in the Western Cape, the province with the lowest mortality rate. HIV/AIDS is the leading cause of premature mortality for all provinces. Mortality due to pre-transitional causes, such as diarrhoea, is more pronounced in the poorer and more rural provinces. In contrast, non-communicable disease mortality is similar across all provinces, although the cause profiles differ. Injury mortality rates are particularly high in provinces with large metropolitan areas and in Mpumalanga. Conclusion. The quadruple burden experienced in all provinces requires a broad range of interventions, including improved access to health care; ensuring that basic needs such as those related to water and sanitation are met; disease and injury prevention; and promotion of a healthy lifestyle. High death rates as a result of HIV/AIDS highlight the urgent need to accelerate the implementation of the treatment and prevention plan. In addition, there is an urgent need to improve the cause-of-death data system to provide reliable cause-of-death statistics at health district level.

A clarion call for action based on refined DALY estimates for South Africa

Initial estimates of the burden of disease in South Africa in 20001 have been revised on the basis of additional data to estimate the disability-adjusted life-years (DALYs) for single causes for the first time in South Africa. The findings highlight the fact that despite uncertainty in the estimates, they provide important information to guide public health responses to improve the health of the nation...

DNA molecules and human therapeutics

Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This review addresses the potential applications of pDNA molecules in vaccine design/development and gene therapy via recombinant DNA technology as well as a staged delivery mechanism for the introduction of plasmid-borne gene to target cells via the nasal route.

Evolution of the docklands food hub : a design-led innovation approach to food sovereignty through local food systems

Access to nutritious, safe and culturally appropriate food is a basic human right (Mechlem, 2004). Food sovereignty defines this right through the empowerment of the people to redefine food and agricultural systems, and through ecologically sustainable production methods. At the heart of the food sovereignty movement are the interests of producers, distributors and consumers, rather than the interests of markets and corporations, which dominate the current globalized food system (Hinrichs, 2003). Food sovereignty challenges designers to enable people to innovate the food system. We are yet to develop economically viable solutions for scaling projects and providing citizens, governments and business with tools to develop and promote projects to innovate food systems and promote food sovereignty (Meroni, 2011; Murray, Caulier-Grice and Mulgan, 2010). This article examines how a design-led approach to innovation can assist in the development of new business models and ventures for local food systems: this is presented through an emerging field of research ‘Design-Led Food Communities’. Design-Led Food Communities enables citizens, governments and business to innovate local food projects through the application of design. This article reports on the case study of the Docklands Food Hub Project in Melbourne, Australia. Preliminary findings demonstrate valued outcomes, but also a deficiency in the design process to generate food solutions collaboratively between government, business and citizens.

From bio-inspired computing to e-Biology

Several algorithms and techniques widely used in Computer Science have been adapted from, or inspired by, known biological phenomena. This is a consequence of the multidisciplinary background of most early computer scientists. The field has now matured, and permits development of tools and collaborative frameworks which play a vital role in advancing current biomedical research. In this paper, we briefly present examples of the former, and elaborate upon two of the latter, applied to immunological modelling and as a new paradigm in gene expression.

Variable phenotype in 16p duplication within a family

Background More individuals are now being identified with very rare genetic syndromes. We present a family with an inherited duplication of 16p11.2 to 16q12.1 in ring formation. Three of the four children, (aged 15 months to 10 years), mother, uncle, and grandmother are affected. Our aim was to provide preliminary evidence of possible phenotypic patterns of learning and behaviour associated with this chromosome anomaly. Method Psychometric assessments were undertaken with all four children. The mother and uncle also agreed to participate in the study. Measures of development (Bayley or Mullen), intellectual ability (WISC-IV or WAIS-III), academic achievement (WIAT-II), adaptive behaviour (Vinelands), and other relevant aspects of functioning (e.g., Children’s Memory Scale) were administered. Results. The first-born child is the only one who is unaffected. Her intellectual ability was assessed as being within the superior range. The second child experienced early difficulties with speech and motor skills. Although his intelligence is average, he has learning difficulties and significant auditory memory problems. The third child’s speech and motor milestones were markedly delayed. He has a complex medical history that includes a vitamin B12 deficiency. On the Mullen Scales at age 4 his scores ranged from average to very low. The development of the youngest child (aged 15 months), who also had a B12 deficiency but was treated early, was assessed as being within typical limits. Conclusions There is considerable developmental variability among the three children with this inherited 16p duplication. We discuss the intriguing similarities and differences, considering common features that may reflect phenotypic patterns and speculating about possible explanations for the variable presentations.

Environmental contributions to autism: Explaining the rise in incidence of autistic spectrum disorders

The incidence of autism spectrum disorders, a heterogenous group of neurodevelopmental disorders is increasing. In response, there has been a concerted effort by researchers to identify environmental risk factors that explain the epidemiological changes seen with autism. Advanced parental age, maternal migrant status, maternal gestational stress, pregnancy and birth complications, maternal obesity and gestational diabetes, maternal vitamin D deficiency, use of antidepressants during gestation and exposure to organochlorine pesticides during pregnancy are all associated with an increased risk of autism. Folic acid use prior to pregnancy may reduce the risk of autism. Exposure to antenatal ultrasonography, maternal gestational cigarette and alcohol use do not appear to influence the risk of autism in offspring. There is little evidence that exposure to environmental toxins such as thimerosal, polybrominated diphenyl ethers and di-(2-ethylhexyl) phthalate in early childhood increases the risk of autism. Apart from birth complications, the current evidence suggests that the majority of environmental factors increasing the risk of autism occur in the antenatal period. Consistent with the rise in incidence in autism, some of these environmental factors are now more common in developed nations. Further research is required to determine how these environmental exposures translate to an increased risk of autism. Understanding how these exposures alter neurodevelopment in autistic children may inform both the aetiopathogenesis and the strategies for prevention of autism.

Molecular characterisation and carotenoid quantification of pro-vitamin A biofortified genetically modified bananas in Uganda

In Uganda, a significant proportion of the population depends on the micronutrient poor East African highland banana as a food staple. Consequently, micronutrient deficiencies such as vitamin A deficiency are an important health concern in the country. To reach most vulnerable rural poor populations, staple crops can be biofortified with essential micronutrients though conventional breeding or genetic engineering. This thesis provided proof of concept that genetically modified East African highland bananas with enhanced provitamin A levels can be generated and fully characterised in Uganda. In addition, provitamin A levels present in popular banana varieties was documented.

Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene

Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.

Quantitative and qualitative impairments in semantic fluency, but not phonetic fluency, as a potential risk factor for Alzheimer's disease

Qualitative aspects of verbal fluency may be more useful in discerning the precise cause of any quantitative deficits in phonetic or category fluency, especially in the case of mild cognitive impairment (MCI), a possible intermediate stage between normal performance and Alzheimer's disease (AD). The aim of this study was to use both quantitative and qualitative (switches and clusters) methods to compare the phonetic and category verbal fluency performance of elderly adults with no cognitive impairment (n = 51), significant memory impairment (n = 16), and AD (n = 16). As expected, the AD group displayed impairments in all quantitative and qualitative measures of the two fluency tasks relative to their age- and education-matched peers. By contrast, the amnestic MCI group produced fewer animal names on the semantic fluency task than controls and showed normal performance on the phonetic fluency task. The MCI group's inferior category fluency performance was associated with a deficit in their category-switching rate rather than word cluster size. Overall, the results indicate that a semantic measure such as category fluency when used in conjunction with a test of episodic memory may increase the sensitivity for detecting preclinical AD. Future research using external cues and other measures of set shifting capacity may assist in clarifying the origin of the amnestic MCI-specific category-switching deficiency. Copyright

In vitro micro propagation of Nicotiana benthamiana via axillary shoots

Axillary shoots of Nicotiana benthamiana were regenerated from nodal explants in two weeks using MS media supplemented with the cytokinin, kinetin (0.5 mg/L), and the auxin, indole-3-butyric acid (IBA) (0.1 mg/L). Ninety two percent of shoots were 2.1-20 mm tall, a size ideal for root induction. After transfer to hormone-free MS they readily produced roots within seven days, with phenotypically normal, fully developed plants being obtained within four weeks. Leaf chlorosis due to iron deficiency was observed in plants over time, however, this was overcome by doubling the concentration of inorganic iron. This rapid micro-propagation system is particularly useful for the in vitro mass production of N. benthamiana plants for various biotechnological applications.

Mutations in the gene encoding IFT dynein complex component WDR34 cause jeune asphyxiating thoracic dystrophy

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Five years of GWAS discovery

The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section. © 2012 The American Society of Human Genetics.