The ethics of surrogate decision making in medicine : autonomy, paternalism, or a different approach?

Knowing who to involve in treatment decisions when a patient is incapacitated has been the subject of discussion in bioethical, health law and clinical research. The major issues tend to revolve around the tension between exercising a degree of medical paternalism and respecting patient autonomy. Patients are encouraged to exert their autonomy even when they may not be capable of doing so, by means of surrogate consent or advanced directives. While liberal concepts of autonomy are exemplified in western bioethics and legal systems, clinically these decisions remain difficult, and input from medical professionals is sought, raising the issue of paternalism. A framework of bioethics, which places the patient in a relational context rather than a strictly autonomous one, may be a more helpful way of deliberating these difficult decisions

Experiential learning styles in the age of a virtual surrogate

There is a long-held sense in general that the increasing use of computers and digital technology changes how a user experiences and learns about the world, not always for the better. This paper reports on a longitudinal study of 245 architecture and construction students over a two year period which examines the impact that virtual reality technologies have on the learning style preferences of students. A series of controlled experiments tests for the impact that increasing exposure to a proprietary virtual reality system has on the mode of learning and learning style preferences of individuals and particular cohorts. The results confirm that when virtual reality applications are used in teaching and learning, the learning behaviours will favour a more concrete experiential mode of learning and a preference for the Accommodator learning style. However, the results also demonstrate, consistently and for the first time, individual students do not privilege any particular mode of learning or learning style preference to any significant extent but rather engage in all modes and represent all learning styles. Novel visualisation techniques are introduced to examine and discuss this contrast.

The effect of exercise and nutrition on the mechanostat

In this review, we discuss the effect of increased and decreased loading and nutrition deficiency on muscle and bone mass and strength (and bone length and architecture) independently and combined. Both exercise and nutrition are integral components of the mechanostat model but both have distinctly different roles. Mechanical strain imparted by muscle action is responsible for the development of the external size and shape of the bone and subsequently the bone strength. In contrast, immobilization during growth results in reduced growth in bone length and a loss of bone strength due to large losses in bone mass (a result of endosteal resorption in cortical bone and trabecular thinning) and changes in geometry (bone shafts do not develop their characteristic shape but rather develop a rounded default shape). The use of surrogate measures for peak muscle forces acting on bone (muscle strength, size, or mass) limits our ability to confirm a cause-and-effect relationship between peak muscle force acting on bone and changes in bone strength. However, the examples presented in this review support the notion that under adequate nutrition, exercise has the potential to increase peak muscle forces acting on bone and thus can lead to a proportional increase in bone strength. In contrast, nutrition alone does not influence muscle or bone in a dose-dependent manner. Muscle and bone are only influenced when there is nutritional deficiency – and in this case the effect is profound. Similar to immobilization, the immediate effect of malnutrition is a reduction in longitudinal growth. More specifically, protein and energy malnutrition results in massive bone loss due to endosteal resorption in cortical bone and trabecular thinning. Unlike loading however, there is indirect evidence that severe malnutrition when associated with menstrual dysfunction can shift the mechanostat set point upward, thus leading to less bone accrual for a given amount of bone strain.

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Objective: To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy.

Design: Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment.

Participants: Patients with any stage of HIV infection who had not received antiretroviral therapy.

Main outcome measures: Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers).
Search strategy: Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001.

Results: 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality.

Conclusions: Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.

A ranking list for information systems journals

There has been an increasing focus internationally on the quality and impact of research outputs in recent years. Several countries, including the United Kingdom and New Zealand have implemented schemes to base the funding of research on research quality. The Australian government is planning to implement a Research Quality Framework (RQF) in the next few years that will impact greatly on funding of research in Australian universities. A key issue for Australian researchers is how the quality and impact of research is defined and measured in their discipline areas. Although peer review is widely used to assess the quality of research outputs, it is expensive and labour intensive. Other surrogate quality measures are often used. This paper focuses on measuring the quality of research outputs in the information systems discipline. We argue that measures such as citation indexes are inappropriate for information systems and that the publication outlet is a more suitable indicator of quality. We present a ranking list of journals for the information systems discipline, and discuss the approach we have taken in developing the list. We discuss how the ranking list may be used in defining and measuring the quality of information systems research outputs, the limitations inherent in the approach and discuss lessons we have learned in developing the list.

Substituted consent : from lunatics to corpses

This analysis traces the origins and evolution of the doctrine of surrogate or substituted judgment, especially its application to medical treatment, including non-therapeutic sterilisation, decisions regarding life and death choices, and more recently, removal of sperm or eggs from incompetent, dying or dead males and females. It argues that the doctrine, which has been acknowledged to be a legal fiction, has an effect of devolving legal and moral responsibility for life and death choices, as well as non-consensual, non-beneficial intrusive procedures, from the competent decision-makers to the incompetent patient. It focuses on the subjective nature of the substituted judgment standard; the problematic nature of evidence propounded to establish the putative choices of the incompetent person; lack of transparency relating to the conflict of interest in the process of substituted judgment decision-making; and the absence of voluntariness, which is an essential element of a valid consent.

The evidence that exercise during growth or adulthood reduces the risk of fragility fractures is weak

There has never been, and will never be, a randomized double-blind placebo-controlled trial demonstrating that exercise in youth, adulthood or old age reduces fragility or osteoporosis-related fractures in old age. The next level of evidence, a randomized, controlled but unblinded study with fractures as an end-point is feasible but has never been done. The basis for the belief that exercise reduces fractures is derived from lower levels of ‘evidence’, namely, retrospective and prospective observation cohort studies and case–control studies. These studies are at best hypothesis generating, never hypothesis testing. They are all subject to many systematic biases and should be interpreted with extreme scepticism. Surrogate measures of anti-fracture efficacy are the next level of evidence, such as the demonstration of a reduction in risk factors for falls, a reduction in falls, a reduction in fractures due to falls, an increase in peak bone size and mass, prevention of bone loss in midlife and restoration of bone mass and structure in old age.

Serum vitamin D and falls in older women in residential care in Australia

Objectives: To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls.

Design: Prospective cohort.

Setting: Residential care facilities for older people in several states of Australia.

Participants: Six hundred sixty-seven women in low-level care and 952 women in high-level care, mean age 83.7 years.

Measurements: Serum 25-hydroxyvitamin D (25D) levels and recognized risk factors for falls including current medication use, a history of previous fractures, weight, tibial length (as a surrogate for height), cognitive function, walking ability, and frequency of going outdoors were determined. The women in low-level care and high-level care were followed for an average of 145 and 168 days, respectively. Falls were recorded prospectively in diaries completed monthly by residential care staff.

Results: Vitamin D deficiency (defined as a serum 25D level below 25 nmol/L) was present in 144 (22%) women in low-level care and 428 (45%) in high-level care. After excluding 358 bed-bound residents and adjusting for weight, cognitive status, psychotropic drug use, previous Colles fracture, and the presence of wandering behavior, log serum 25D level remained independently associated with time to first fall. The adjusted hazards ratio was 0.74 (95% confidence interval=0.59–0.94; P=.01), implying a 20% reduction in the risk of falling with a doubling of the vitamin D level.

Conclusion: Vitamin D deficiency is common in residential care in Australia. A low level of serum vitamin D is an independent predictor of incident falls.

Use of in vitro critical inhibitory concentration, a novel approach to predict in vivo synergistic bactericidal effect of combined amikacin and piperacillin against pseudomonas aeruginosa in a systemic rat infection model

PURPOSE: This study was undertaken to explore the use of in vitro critical inhibitory concentration (CIC) as a surrogate marker relating the pharmacokinetic (PK) parameters to in vivo bactericidal synergistic effect [pharmacodynamic (PD)] of amikacin + piperacillin combination against Pseudomonas aeruginosa in a systemic rat infection model. METHODS: The in vitro antibacterial activities of amikacin and piperacillin, alone and in combinations at various ratios of the concentrations, were tested against a standard [5 x 10(5) colony-forming units (CFU)/ml] and a large (1.5 x 10(8) CFU/ml) inoculum of P. aeruginosa ATCC 9027 using a modified survival-time method. The CIC of each individual antibiotic for the different combinations was determined using a cup-plate method. In vivo studies were performed on Sprague-Dawley rats using a systemic model of infection with P. aeruginosa ATCC 9027. PK profiles and in vivo killing effects of the combination at different dosing ratios were studied. RESULTS: An inoculum effect was observed with the antibiotics studied. Synergy was seen against both the inocula at the following concentration ratios: 70% C(ami) + 30% C(pip) and 75% C(ami) + 25% C(pip), where C(ami) and C(pip) are the concentrations of amikacin and piperacillin to produce a 1000-fold decrease in bacterial population over 5 h, respectively. The CIC values determined corroborated with the order of in vitro bacterial killing observed for the antibiotic combinations. The dosing ratio of 12.6 mg/kg amikacin + 36 mg/kg piperacillin (a 70:30 ratio of the individual doses) exhibited the greatest killing in vivo when compared to the other ratios. The PK-PD relationships were described by simple, linear regression equations using the area under the in vivo killing curve as a PD marker and the AUCIC(ami)/CIC(ami) + AUCIC(pip)/CIC(pip), AUC(ami)/CIC(ami) + AUC(pip)/CIC(pip), C(max,ami)/CIC(ami) + C(max,pip)/CIC(pip), and AUCIC(ami)/MIC(ami) + AUCIC(pip)/MIC(pip) as PK markers for the amikacin + piperacillin combination. CONCLUSION: The combination of amikacin and piperacillin exhibited synergistic killing effect on P. aeruginosa that could be modeled using CIC as a surrogate marker relating the PK parameters to in vivo bactericidal effect.

Deterministic versus stochastic quantitative microbial Risk Assessment models for wastewater irrigation of food crops

Reuse of wastewater to irrigate food crops is being practiced in many parts of the world and is becoming more commonplace as the competition for, and stresses on, freshwater resources intensify. But there are risks associated with wastewater irrigation, including the possibility of transmission of pathogens causing infectious disease, to both workers in the field and to consumers buying and eating produce irrigated with wastewater. To manage these risks appropriately we need objective and quantitative estimates of them. This is typically achieved through one of two modelling approaches: deterministic or stochastic. Each parameter in a deterministic model is represented by a single value, whereas in stochastic models probability functions are used. Stochastic models are theoretically superior because they account for variability and uncertainty, but they are computationally demanding and not readily accessible to water resource and public health managers. We constructed models to estimate risk of enteric virus infection arising from the consumption of wastewater-irrigated horticultural crops (broccoli, cucumber and lettuce), and compared the resultant levels of risk between the deterministic and stochastic approaches. Several scenarios were tested for each crop, accounting for different concentrations of enteric viruses and different lengths of environmental exposure (i.e. the time between the last irrigation event and harvest, when the viruses are liable to decay or inactivation). In most situations modelled the two approaches yielded similar estimates of risk (within 1 order-of-magnitude). The two methods diverged most markedly, up to around 2 orders-of-magnitude, when there was large uncertainty associated with the estimate of virus concentration and the exposure period was short (1 day). Therefore, in some circumstances deterministic modelling may offer water resource managers a pragmatic alternative to stochastic modelling, but its usefulness as a surrogate will depend upon the level of uncertainty in the model parameters.

Food security measurement in cultural pluralism : missing the point or conceptual misunderstanding?

Objective : Food Security has become a global concern, yet its measurement has varied considerably across disciplines and countries. We examined the current discrepancies in the definitions of food security and propose a framework for understanding and measuring food security.

Methods : This conceptual review draws from a range of works published in Medline and the gray literature to advance the understanding of food security concepts. We begin by examining the historical background of food security and then move on to examine its various definitions and interpret food through cultural lenses in terms of food access and utilization. We finish by examining various measurements and indicators of food security and reviewing implications for public health.

Results : We argue that the reliance on coping strategies as surrogate measurements of food insecurity without taking into account the social, cultural, and political contexts in which they occur is misleading, and viewing food insecurity solely from a food access or availability perspective, without taking into account food utilization and asset creation as pillars of food security, paints an incomplete picture. Although this review does not claim to provide solutions to the discrepancies in the conceptual definition of food security, it attempts to highlights areas of concern and provide a way forward.

Conclusion : When coping strategies are used as an indicator of food insecurity, they need to be culturally relevant and focus tested, and together with objective measurements of nutritional outcomes, would allow policy makers to make evidence-based decisions to inform social and nutrition policies.

Habitat use by five sympatric Australian freshwater crayfish species (Parastacidae)

1. The Grampians National Park in Victoria is a 'hot spot' for freshwater crayfish diversity, with seven species from six genera occurring in sympatry. Few studies have examined how multiple species of freshwater crayfish co-exist across landscapes consisting of a mosaic of perennial and seasonal habitats. Despite their endemicity and likely key role in freshwaters, the ecology and biology of these crayfish remains unknown.

2. This study determined the distribution and habitat use of five crayfish species (Euastacus bispinosus, Cherax destructor, Geocharax falcata, Gramastacus insolitus and Engaeus lyelli). Seasonal sampling surveys ascertained whether crayfish distribution was related to habitat type, environmental or physicochemical variables, catchment or season.

3. Distribution was directly related to habitat type and the environmental and physicochemical variables that characterised habitats. Engaeus lyelli, G. falcata and G. insolitus occurred predominantly in floodplain wetlands and flooded vegetation habitats, E. bispinosus occurred only in flowing soft-sediment channels and C. destructor was found in all catchments and habitat types studied. Gramastacus insolitus co-occurred with G. falcata at all sites except two, so no distinct habitat separations were apparent for these two species.

4. A high percentage cover of boulders was the best indicator of crayfish absence, and discriminated between habitat types and crayfish species: it was probably a surrogate for a larger range of environmental and physicochemical variables. Catchment and season did not affect crayfish distribution.

5. These crayfish species varied in their degree of habitat specialisation from strongly generalist (C. destructor) to occupying only a specific habitat type (E. bispinosus). Some species appeared specialised for seasonal wetlands (G. insolitus and G. falcata). Overlap in site occupancy also varied: G. insolitus and G. falcata distributions were strongly associated, whereas C. destructor appeared to occur opportunistically across habitats, both alone and co-occurring with all the other species.

6. Management strategies to conserve multiple species of crayfish co-existing within landscapes will need to incorporate a range of perennial and seasonal habitat types to ensure sufficient space is available for species to maintain different occupancy patterns. Given that water resources are under increasing pressure and are strongly regulated within the Grampians National Park, this may present a conservation challenge to water managers in this location.

Evaluation of heat stress indices using physiological comparisons in an alumina refinery in a sub-tropical climate

The production of alumina involves the use of a process known as the Bayer process. This method involves the digestion of raw bauxite in sodium hydroxide at temperatures around 250°C. The resultant pregnant liquor then goes through a number of filtering and precipitation processes to obtain the aluminium oxide crystals which are then calcined to obtain the final product. The plant is situated in a sub tropical climate in Northern Australia and this combined with the hot nature of the process results in a potential for heat related illnesses to develop. When assessing a work environment for heat stress a heat stress index is often employed as a guideline and to date the Wet Bulb Globe Temperature (WBGT) has been the recommended index. There have been concerns over the past that the WBGT is not suited to the Northern Australian climate and in fact studies in other countries have suggested this is the case. This study was undertaken in the alumina plant situated in Gladstone Queensland to assess if WBGT was in fact the most suitable index for use or if another was more applicable. To this end three indices, Wet Bulb Globe Temperature (WBGT), Heat Stress Index (HSI) and Required Sweat Rate (SWreq) were compared and assessed using physiological monitoring of heart rate and surrogate core temperature. A number of different jobs and locations around the plant were investigated utilising personal and environmental monitoring equipment. These results were then collated and analysed using a computer program written as part of the study for the manipulation of the environmental data . Physiological assessment was carried out using methods approved by international bodies such as National Institute for Occupational Safety & Health (NIOSH) and International Standards Organisation (ISO) and incorporated the use of a ‘Physiological Factor’ developed to enable the comparison of predicted allowable exposure times and strain on the individual. Results indicated that of the three indices tested, Required Sweat Rate was found to be the most suitable for the climate and in the environment of interest. The WBGT system was suitable in areas in the moderate temperature range (ie 28 to 32°C) but had some deficiencies above this temperature or where the relative humidity exceeded approximately 80%. It was however suitable as a first estimate or first line indicator. HSI over-estimated the physiological strain in situations of high temperatures, low air flows and exaggerated the benefit of artificial air flows on the worker in certain environments ie. fans.

Corporate governance structure and firm performance : empirical evidence from Brusa Malaysia, Kuala Lumper

The issue of corporate governance has been emerging as important phenomena that has been searched extensively both in developed countries due to its strategic impact on the monitoring of management activities and firms’ performance. Yet little attempt has been made in developing countries like Malaysia to ascertain what constitute corporate governance and its impact on firm's performance. Therefore, this study aims at examining the structure of the corporate governance and its impact on firm’s performance. This study is based on 100 firms, which are the component of the Composite Index (CI) serve as market barometer. This study employs cross-sectional annual multiple regression model to examine, what constitutes the corporate governance structure and its impact on performance of the firm. The analysis was based on annual regression over 5 years period from 1997 through 2001. Three different blend of surrogate for corporate governance were developed for good corporate governance structure. These are the independent non-executive (outside) directors, audit committee and remuneration committee. To isolate the size effect from the impact of corporate governance structure on firm’s performance, firm’s size was also included are variable in the model. The ratio of net income before tax to total asset is used as a surrogate for firm’s performance. Evidence from the study indicates that there is partial relation between corporate governance structure and corporate performance. The presence of both audit and remuneration committee serves as an important monitoring device to control management activities that lead to increase firm's performance. While on average, the presence of independent nonexecutive directors does not provide any significant explanation for the firm's performance. However, the firm size appears to have significant impact on corporate performance.