Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies

BACKGROUND Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. METHODS AND FINDINGS Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations. CONCLUSIONS South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.

A quality of life subscale for terminally ill cancer patients

A subscale was developed to assess the quality of life of cancer patients with a life expectancy of six months or less. Phase I of this study identified the major concerns of 74 terminally ill cancer patients (19 with breast cancer, 19 with lung cancer, 18 with colorectal cancer, 9 with renal cell cancer, 9 with prostate cancer), 39 family caregivers, and 20 health care professionals. Patients interviewed were being treated at the University of Texas M. D. Anderson Cancer Center or at the Hospice at the Texas Medical Center in Houston. In Phase II, 120 patients (30 with breast cancer, 30 with lung cancer, 30 with colorectal cancer, 15 with prostate cancer, and 15 with renal cell cancer) rated the importance of these concerns for quality of life. Items retained for the subscale were rated as "extremely important" or "very important" by at least 60% of the sample and were reported as being applicable by at least two-thirds of the sample. The 61 concerns that were identified were formatted as a questionnaire for Phase III. In Phase III, 356 patients (89 with breast cancer, 88 with lung cancer, 88 with colorectal cancer, 44 with prostate cancer, and 47 with renal cell cancer) were interviewed to determine the subscale's reliability and sensitivity to change in clinical status. Both factor analysis and item response theory supported the inclusion of the same 35 items for the subscale. Internal consistency reliability was moderate to high for the subscale's domains: spiritual (0.87), existential (0.76), medical care (0.68), symptoms (0.67), social/family (0.66), and emotional (0.61). Test-retest correlation coefficients also were high for the domains: social/family (0.86), emotional (0.83), medical care (0.83), spiritual (0.75), existential (0.75), and symptoms (0.81).^ In addition, concurrent validity was supported by the high correlation between the subscale's symptom domain and symptom items from the European Organization for Research and Treatment of Cancer (EORTC) scale (r = 0.74). Patients' functional status was assessed with the Eastern Cooperative Oncology Group (ECOG) Performance status rating. When ECOG categories were compared to subscale domains, patients who scored lower in functional status had lower scores in the spiritual, existential, social/family, and emotional domains. Patients who scored lower in physical well-being had higher scores in the symptom domain. Patient scores in the medical care domain were similar for each ECOG category. The results of this study support the subscale's use in assessing quality of life and the outcomes of palliative treatment for cancer patients in their last six months of life. ^

Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress.

We have discovered that three longevity mutants of the nematode Caenorhabditis elegans also exhibit increased intrinsic thermotolerance (Itt) as young adults. Mutation of the age-1 gene causes not only 65% longer life expectancy but also Itt. The Itt phenotype cosegregates with age-1. Long-lived spe-26 and daf-2 mutants also exhibit Itt. We investigated the relationship between increased thermotolerance and increased life-span by developing conditions for environmental induction of thermotolerance. Such pretreatments at sublethal temperatures induce significant increases in thermotolerance and small but statistically highly significant increases in life expectancy, consistent with a causal connection between these two traits. Thus, when an animal's resistance to stress is increased, by either genetic or environmental manipulation, we also observe an increase in life expectancy. These results suggest that ability to respond to stress limits the life expectancy of C. elegans and might do so in other metazoa as well.

Statistical bulletin - Metropolitan Life.

Index medicus

Extending the human life span : social policy and social ethics /

"NSF/RA 770123."

End-of-life decision making in Europe and Australia - A physician survey

Background: The frequencies with which physicians make different medical end-of-life decisions (ELDs) may differ between countries, but comparison between countries has been difficult owing to the use of dissimilar research methods. Methods: A written questionnaire was sent to a random sample of physicians from 9 specialties in 6 European countries and Australia to investigate possible differences in the frequencies of physicians' willingness to perform ELDs and to identify predicting factors. Response rates ranged from 39% to 68% (N= 10 139). Using hypothetical cases, physicians were asked whether they would ( probably) make each of 4 ELDs. Results: In all the countries, 75% to 99% of physicians would withhold chemotherapy or intensify symptom treatment at the request of a patient with terminal cancer. In most cases, more than half of all physicians would also be willing to deeply sedate such a patient until death. However, there was generally less willingness to administer drugs with the explicit intention of hastening death at the request of the patient. The most important predictor of ELDs was a request from a patient with decisional capacity (odds ratio, 2.1-140.0). Shorter patient life expectancy and uncontrollable pain were weaker predictors but were more stable across countries and across the various ELDs (odds ratios, 1.1-2.4 and 0.9-2.4, respectively). Conclusion: Cultural and legal factors seem to influence the frequencies of different ELDs and the strength of their determinants across countries, but they do not change the essence of decision making.

Predictive Models for Tomato Spotted Wilt Virus Spread Dynamics, Considering Frankliniella occidentalis Specific Life Processes as Influenced by the Virus

Several models have been studied on predictive epidemics of arthropod vectored plant viruses in an attempt to bring understanding to the complex but specific relationship between the three cornered pathosystem (virus, vector and host plant), as well as their interactions with the environment. A large body of studies mainly focuses on weather based models as management tool for monitoring pests and diseases, with very few incorporating the contribution of vector's life processes in the disease dynamics, which is an essential aspect when mitigating virus incidences in a crop stand. In this study, we hypothesized that the multiplication and spread of tomato spotted wilt virus (TSWV) in a crop stand is strongly related to its influences on Frankliniella occidentalis preferential behavior and life expectancy. Model dynamics of important aspects in disease development within TSWV-F. occidentalis-host plant interactions were developed, focusing on F. occidentalis' life processes as influenced by TSWV. The results show that the influence of TSWV on F. occidentalis preferential behaviour leads to an estimated increase in relative acquisition rate of the virus, and up to 33% increase in transmission rate to healthy plants. Also, increased life expectancy; which relates to improved fitness, is dependent on the virus induced preferential behaviour, consequently promoting multiplication and spread of the virus in a crop stand. The development of vector-based models could further help in elucidating the role of tri-trophic interactions in agricultural disease systems. Use of the model to examine the components of the disease process could also boost our understanding on how specific epidemiological characteristics interact to cause diseases in crops. With this level of understanding we can efficiently develop more precise control strategies for the virus and the vector.

A 'slow pace of life' in Australian old-endemic passerine birds is not accompanied by low basal metabolic rates

Life history theory suggests that species experiencing high extrinsic mortality rates allocate more resources toward reproduction relative to self-maintenance and reach maturity earlier ('fast pace of life') than those having greater life expectancy and reproducing at a lower rate ('slow pace of life'). Among birds, many studies have shown that tropical species have a slower pace of life than temperate-breeding species. The pace of life has been hypothesized to affect metabolism and, as predicted, tropical birds have lower basal metabolic rates (BMR) than temperate-breeding birds. However, many temperate-breeding Australian passerines belong to lineages that evolved in Australia and share 'slow' life-history traits that are typical of tropical birds. We obtained BMR from 30 of these 'old-endemics' and ten sympatric species of more recently arrived passerine lineages (derived from Afro-Asian origins or introduced by Europeans) with 'faster' life histories. The BMR of 'slow' temperate-breeding old-endemics was indistinguishable from that of new-arrivals and was not lower than the BMR of 'fast' temperate-breeding non-Australian passerines. Old-endemics had substantially smaller clutches and longer maximal life spans in the wild than new arrivals, but neither clutch size nor maximum life span was correlated with BMR. Our results suggest that low BMR in tropical birds is not functionally linked to their 'slow pace of life' and instead may be a consequence of differences in annual thermal conditions experienced by tropical versus temperate species.

The way forward : report on the preparatory phase of prefabricated building design and construction methodology: identifying critical issues and recommending the way forward

This is an initial report of the PolyU SD part of the team to study Pre-fabricated Building Design and Construction Methodology and marks the completion of Phase 1. It follows our first notes prepared for the meeting on 2 February that identified some critical issues including future lifestyles, life expectancy of buildings, sustainability, size, flexibility and planning considerations. It is also an expansion of our presentation in Dongguan on 23 February. It is not a comprehensive survey of existing approaches or possible ways forward, but it has homed in on certain specific issues and does give specific examples to make the suggestions concrete. It is recommended that more comprehensive research be done to establish previous work and experience internationally. It is also recommended that more research be done on lifestyles as a preliminary to developing at least three concepts for evaluation before proceeding to the detailed design of one concept for full prototyping and market testing. The goal at this point is not to define a single direction but to suggest several future trajectories for further consideration. By the same token, this report is not intended as an exhaustive description of the considerable base of knowledge and ideas brought by the PolyU team to this exciting task. Before taking on an issue of this magnitude and importance in the definition of Hong Kong's future, one must carry out a thoughtful analysis of the issues at hand and an informed definition of paradigms, directions, goals and methods whereby our energies can be best used in the next steps. This report is the result of this analysis

Simulation and development of a mock circulation loop with variable compliance

Heart disease is attributed as the highest cause of death in the world. Although this could be alleviated by heart transplantation, there is a chronic shortage of donor hearts and so mechanical solutions are being considered. Currently, many Ventricular Assist Devices (VADs) are being developed worldwide in an effort to increase life expectancy and quality of life for end stage heart failure patients. Current pre-clinical testing methods for VADs involve laboratory testing using Mock Circulation Loops (MCLs), and in vivo testing in animal models. The research and development of highly accurate MCLs is vital to the continuous improvement of VAD performance. The first objective of this study was to develop and validate a mathematical model of a MCL. This model could then be used in the design and construction of a variable compliance chamber to improve the performance of an existing MCL as well as form the basis for a new miniaturised MCL. An extensive review of literature was carried out on MCLs and mathematical modelling of their function. A mathematical model of a MCL was then created in the MATLAB/SIMULINK environment. This model included variable features such as resistance, fluid inertia and volumes (resulting from the pipe lengths and diameters); compliance of Windkessel chambers, atria and ventricles; density of both fluid and compressed air applied to the system; gravitational effects on vertical columns of fluid; and accurately modelled actuators controlling the ventricle contraction. This model was then validated using the physical properties and pressure and flow traces produced from a previously developed MCL. A variable compliance chamber was designed to reproduce parameters determined by the mathematical model. The function of the variability was achieved by controlling the transmural pressure across a diaphragm to alter the compliance of the system. An initial prototype was tested in a previously developed MCL, and a variable level of arterial compliance was successfully produced; however, the complete range of compliance values required for accurate physiological representation was not able to be produced with this initial design. The mathematical model was then used to design a smaller physical mock circulation loop, with the tubing sizes adjusted to produce accurate pressure and flow traces whilst having an appropriate frequency response characteristic. The development of the mathematical model greatly assisted the general design of an in vitro cardiovascular device test rig, while the variable compliance chamber allowed simple and real-time manipulation of MCL compliance to allow accurate transition between a variety of physiological conditions. The newly developed MCL produced an accurate design of a mechanical representation of the human circulatory system for in vitro cardiovascular device testing and education purposes. The continued improvement of VAD test rigs is essential if VAD design is to improve, and hence improve quality of life and life expectancy for heart failure patients.

Biotribological assessment for artificial synovial joints : the role of boundary lubrication

Biotribology, the study of lubrication, wear and friction within the body, has become a topic of high importance in recent times as we continue to encounter debilitating diseases and trauma that destroy function of the joints. A highly successful surgical procedure to replace the joint with an artificial equivalent alleviates dysfunction and pain. However, the wear of the bearing surfaces in prosthetic joints is a significant clinical problem and more patients are surviving longer than the life expectancy of the joint replacement. Revision surgery is associated with increased morbidity and mortality and has a far less successful outcome than primary joint replacement. As such, it is essential to ensure that everything possible is done to limit the rate of revision surgery. Past experience indicates that the survival rate of the implant will be influenced by many parameters, of primary importance, the material properties of the implant, the composition of the synovial fluid and the method of lubrication. In prosthetic joints, effective boundary lubrication is known to take place. The interaction of the boundary lubricant and the bearing material is of utmost importance. The identity of the vital active ingredient within synovial fluid (SF) to which we owe the near frictionless performance of our articulating joints has been the quest of researchers for many years. Once identified, tribo tests can determine what materials and more importantly what surfaces this fraction of SF can function most optimally with. Surface-Active Phospholipids (SAPL) have been implicated as the body’s natural load bearing lubricant. Studies in this thesis are the first to fully characterise the adsorbed SAPL detected on the surface of retrieved prostheses and the first to verify the presence of SAPL on knee prostheses. Rinsings from the bearing surfaces of both hip and knee prostheses removed from revision operations were analysed using High Performance Liquid Chromatography (HPLC) to determine the presence and profile of SAPL. Several common prosthetic materials along with a novel biomaterial were investigated to determine their tribological interaction with various SAPLs. A pin-on-flat tribometer was used to make comparative friction measurements between the various tribo-pairs. A novel material, Pyrolytic Carbon (PyC) was screened as a potential candidate as a load bearing prosthetic material. Friction measurements were also performed on explanted prostheses. SAPL was detected on all retrieved implant bearing surfaces. As a result of the study eight different species of phosphatidylcholines were identified. The relative concentrations of each species were also determined indicating that the unsaturated species are dominant. Initial tribo tests employed a saturated phosphatidylcholine (SPC) and the subsequent tests adopted the addition of the newly identified major constituents of SAPL, unsaturated phosphatidylcholine (USPC), as the test lubricant. All tribo tests showed a dramatic reduction in friction when synthetic SAPL was used as the lubricant under boundary lubrication conditions. Some tribopairs showed more of an affinity to SAPL than others. PyC performed superior to the other prosthetic materials. Friction measurements with explanted prostheses verified the presence and performance of SAPL. SAPL, in particular phosphatidylcholine, plays an essential role in the lubrication of prosthetic joints. Of particular interest was the ability of SAPLs to reduce friction and ultimately wear of the bearing materials. The identification and knowledge of the lubricating constituents of SF is invaluable for not only the future development of artificial joints but also in developing effective cures for several disease processes where lubrication may play a role. The tribological interaction of the various tribo-pairs and SAPL is extremely favourable in the context of reducing friction at the bearing interface. PyC is highly recommended as a future candidate material for use in load bearing prosthetic joints considering its impressive tribological performance.

The contribution of physical activity and sedentary behaviours to the growth and development of children and adolescents : implications for overweight and obesity

The obesity epidemic is a global trend and is of particular concern in children. Recent reports have highlighted the severity of obesity in children by suggesting: “today's generation of children will be the first for over a century for whom life expectancy falls.” This review assesses the evidence that identifies the important role of physical activity in the growth, development and physical health of young people, owing to its numerous physical and psychological health benefits. Key issues, such as “does a sedentary lifestyle automatically lead to obesity” and “are levels of physical activity in today's children less than physical activity levels in children from previous generations?”, are also discussed. Today's environment enforces an inactive lifestyle that is likely to contribute to a positive energy balance and childhood obesity. Whether a child or adolescent, the evidence is conclusive that physical activity is conducive to a healthy lifestyle and prevention of disease. Habitual physical activity established during the early years may provide the greatest likelihood of impact on mortality and longevity. It is evident that environmental factors need to change if physical activity strategies are to have a significant impact on increasing habitual physical activity levels in children and adolescents. There is also a need for more evidence-based physical activity guidelines for children of all ages. Efforts should be concentrated on facilitating an active lifestyle for children in an attempt to put a stop to the increasing prevalence of obese children

Characterising the homeostatic and hedonic markers of the susceptible phenotype

Over the years, approaches to obesity prevention and treatment have gone from focusing on genetic and other biological factors to exploring a diversity of diets and individual behavior modification interventions anchored primarily in the power of the mind, to the recent shift focusing on societal interventions to design ";temptation-proof"; physical, social, and economic environments. In spite of repeated calls to action, including those of the World Health Organization (WHO), the pandemic continues to progress. WHO recently projected that if the current lifestyle trend in young and adult populations around the world persist, by 2012 in countries like the USA, health care costs may amount to as much as 17.7% of the GDP. Most importantly, in large part due to the problems of obesity, those children may be the first generation ever to have a shorter life expectancy than that of their parents. This work presents the most current research and proposals for addressing the pandemic. Past studies have focused primarly on either genetic or behavioral causes for obesity, however today's research indicates that a strongly integrated program is the best prospect for success in overcoming obesity. Furthermore, focus on the role of society in establishing an affordable, accessible and sustainable program for implementing these lifestyle changes is vital, particularly for those in economically challenged situations, who are ultimately at the highest risk for obesity. Using studies from both neuroscience and behavioral science to present a comprehensive overview of the challenges and possible solutions, The brain-to-society approach to obesity prevention focuses on what is needed in order to sustain a healthy, pleasurable and affordable lifestyle.

Renewing concrete sleepers : how long can they last?

The paper explores the way in which the life of concrete sleepers can be dramatically affected by two important factors, namely impact forces and fatigue cycles. Drawing on the very limited experimental and field data currently available about these two factors, the paper describes detailed simulations of sleepers in a heavy haul track in Queensland Australia over a period of 100 years. The simulation uses real wheel/rail impact force records from that track, together with data on static bending tests of similar sleepers and preliminary information on their impact vs static strength. The simulations suggest that despite successful performance over many decades, large unplanned replacement costs could be imminent, especially considering the increasingly demanding operational conditions sleepers have sustained over their life. The paper also discusses the key factors track owners need to consider in attempting to plan for these developments.

Resorbable composite scaffolds for craniofacial bone tissue engineering

Aim: Bone loss associated with trauma, osteo-degenerative diseases and tumors has tremendous socioeconomic impact related to personal and occupation disability and health care costs. In the present climate of increasing life expectancy with an ensuing increase in bone-related injuries, orthopaedic surgery is undergoing a paradigm shift from bone-grafting to bone engineering, where a scaffold is implanted to provide adequate load bearing and enhance tissue regeneration. We aim to develop composite scaffolds for bone tissue engineering applications to replace the current gold standard of autografting. ---------- Methods: Medical grade polycaprolactone-tricalcium phosphate (mPCL/TCP) scaffolds (80/20 wt%) were custom made using fused deposition modelling to produce 1x1.5x2 cm sized implants for critical-sized pig cranial implantations, empty defects were used as a control. Autologous bone marrow stromal cells (BMSCs) were extracted and precultured for 2 weeks, dispersed within fibrin glue and injected during scaffold implantation. After 2 years, microcomputed tomography and histology were used to assess bone regenerative capabilities of cell versus cell-free scaffolds. ---------- Results: Extensive bone regeneration was evident throughout the entire scaffold. Clear osteocytes embedded within mineralised matrix and active osteoblasts present around scaffold struts were observed. Cell groups performed better than cell-free scaffolds. ---------- Conclusions: Bone regeneration within defects which cannot heal unassisted can be achieved using mPCL/TCP scaffolds. This is improved by the inclusion of autogenous BMSCs. Further work will include the inclusion of growth factors including BMP-2, VEGF and PDGF to provide multifunctional scaffolds, where the three-dimensional (3D) template itself acts as a biomimetic, programmable and multi-drug delivery device.