A cost-effectiveness analysis of a telephone-linked care intervention for individuals with Type 2 diabetes

AIM: To assess the cost-effectiveness of an automated telephone-linked care intervention, Australian TLC Diabetes, delivered over 6 months to patients with established Type 2 diabetes mellitus and high glycated haemoglobin level, compared to usual care. METHODS: A Markov model was designed to synthesize data from a randomized controlled trial of TLC Diabetes (n=120) and other published evidence. The 5-year model consisted of three health states related to glycaemic control: 'sub-optimal' HbA1c ≥58mmol/mol (7.5%); 'average' ≥48-57mmol/mol (6.5-7.4%) and 'optimal' <48mmol/mol (6.5%) and a fourth state 'all-cause death'. Key outcomes of the model include discounted health system costs and quality-adjusted life years (QALYS) using SF-6D utility weights. Univariate and probabilistic sensitivity analyses were undertaken. RESULTS: Annual medication costs for the intervention group were lower than usual care [Intervention: £1076 (95%CI: £947, £1206) versus usual care £1271 (95%CI: £1115, £1428) p=0.052]. The estimated mean cost for intervention group participants over five years, including the intervention cost, was £17,152 versus £17,835 for the usual care group. The corresponding mean QALYs were 3.381 (SD 0.40) for the intervention group and 3.377 (SD 0.41) for the usual care group. Results were sensitive to the model duration, utility values and medication costs. CONCLUSION: The Australian TLC Diabetes intervention was a low-cost investment for individuals with established diabetes and may result in medication cost-savings to the health system. Although QALYs were similar between groups, other benefits arising from the intervention should also be considered when determining the overall value of this strategy.

Structure and palaeoenvironmental implications of inter-branch coenosteum-rich skeleton in corymbose Acropora species

Coral reefs provide an increasingly important archive of palaeoclimate data that can be used to constrain climate model simulations. Reconstructing past environmental conditions may also provide insights into the potential of reef systems to survive changes in the Earth’s climate. Reef-based palaeoclimate reconstructions are predominately derived from colonies of massive Porites, with the most abundant genus in the Indo-Pacific—Acropora—receiving little attention owing to their branching growth trajectories, high extension rates and secondary skeletal thickening. However, inter-branch skeleton (consisting of both coenosteum and corallites) near the bases of corymbose Acropora colonies holds significant potential as a climate archive. This region of Acropora skeleton is atypical, having simple growth trajectories with parallel corallites, approximately horizontal density banding, low apparent extension rates and a simple microstructure with limited secondary thickening. Hence, inter-branch skeleton in Acropora bears more similarities to the coralla of massive corals, such as Porites, than to traditional Acropora branches. Cyclic patterns of Sr/Ca ratios in this structure suggest that the observed density banding is annual in nature, thus opening up the potential to use abundant corymbose Acropora for palaeoclimate reconstruction.

The biology of an isolated population of American Flamingo Phoenicopterus ruber in the Galapagos Islands

A genetically and morphologically divergent population of c.500 American Flamingos, isolated from the parental Caribbean stock of Phoenicopterus ruber, occurs in the Galapagos archipelago. Based primarily on data from a 3-year study, we provide the first description of the feeding and breeding biology of this population. Galapagos provides a suitable habitat comprising lagoons on a number of islands, among which the flamingos travel in response to food and nest site availability. The occurrence and qualnity of some food species was associated with the chlorosity of lagoon water, as was the distribution of flamingos. They bred opportunistically at five lagoons on four islands, sometimes simultaneously on more than one island. Group display usually involved approx 20 birds and colonies contained as few as three nests. Laying occurred during nine months of the year... We review potential dangers to this unique population and suggest conservation measures.

Retinal anatomy of the New Zealand kiwi: Structural traits consistent with their nocturnal behavior

Kiwi (Apteryx spp.) have a visual system unlike that of other nocturnal birds, and have specializations to their auditory, olfactory and tactile systems. Eye size, binocular visual fields and visual brain centers in kiwi are proportionally the smallest yet recorded among birds. Given the many unique features of the kiwi visual system, we examined the laminar organization of the kiwi retina to determine if they evolved increased light sensitivity with a shift to a nocturnal niche or if they retained features of their diurnal ancestor. The laminar organization of the kiwi retina was consistent with an ability to detect low light levels similar to that of other nocturnal species. In particular, the retina appeared to have a high proportion of rod photoreceptors compared to diurnal species, as evidenced by a thick outer nuclear layer, and also numerous thin photoreceptor segments intercalated among the conical shaped cone photoreceptor inner segments. Therefore, the retinal structure of kiwi was consistent with increased light sensitivity, although other features of the visual system, such as eye size, suggest a reduced reliance on vision. The unique combination of a nocturnal retina and smaller than expected eye size, binocular visual fields and brain regions make the kiwi visual system unlike that of any bird examined to date. Whether these features of their visual system are an evolutionary design that meets their specific visual needs or are a remnant of a kiwi ancestor that relied more heavily on vision is yet to be determined.

Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli

The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche.

Vocal repertoire of the New Zealand kea parrot Nestor notabilis

The unique alpine-living kea parrot Nestor notabilis has been the focus of numerous cognitive studies, but its communication system has so far been largely neglected. We examined 2,884 calls recorded in New Zealand’s Southern Alps. Based on audio and visual spectrographic differences, these calls were categorised into seven distinct call types: the non-oscillating ‘screech’ contact call and ‘mew’; and the oscillating ‘trill’, ‘chatter’, ‘warble’ and ‘whistle’; and a hybrid ‘screech-trill’. Most of these calls contained aspects that were individually unique, in addition to potentially encoding for an individual’s sex and age. Additionally, for each recording, the sender’s previous and next calls were noted, as well as any response given by conspecifics. We found that the previous and next calls made by the sender were most often of the same type, and that the next most likely preceding and/or following call type was the screech call, a contact call which sounds like the ‘kee-ah’ from which the bird’s name derives. As a social bird capable of covering large distances over visually obstructive terrain, long distance contact calls may be of considerable importance for social cohesion. Contact calls allow kea to locate conspecifics and congregate in temporary groups for social activities. The most likely response to any given call was a screech, usually followed by the same type of call as the initial call made by the sender, although responses differed depending on the age of the caller. The exception was the warble, the kea’s play call, to which the most likely response was another warble. Being the most common call type, as well as the default response to another call, it appears that the ‘contagious’ screech contact call plays a central role in kea vocal communication and social cohesion

Evolution of brain size in the palaeognath lineage, with an emphasis on New Zealand ratites

Brain size in vertebrates varies principally with body size. Although many studies have examined the variation of brain size in birds, there is little information on Palaeognaths, which include the ratite lineage of kiwi, emu, ostrich and extinct moa, as well as the tinamous. Therefore, we set out to determine to what extent the evolution of brain size in Palaeognaths parallels that of other birds, i. e., Neognaths, by analyzing the variation in the relative sizes of the brain and cerebral hemispheres of several species of ratites and tinamous. Our results indicate that the Palaeognaths possess relatively smaller brains and cerebral hemispheres than the Neognaths, with the exception of the kiwi radiation (Apteryx spp.). The external morphology and relatively large size of the brain of Apteryx, as well as the relatively large size of its telencephalon, contrast with other Palaeognaths, including two species of historically sympatric moa, suggesting that unique selective pressures towards increasing brain size accompanied the evolution of kiwi. Indeed, the size of the cerebral hemispheres with respect to total brain size of kiwi is rivaled only by a handful of parrots and songbirds, despite a lack of evidence of any advanced behavioral/ cognitive abilities such as those reported for parrots and crows. In addition, the enlargement in brain and telencephalon size of the kiwi occurs despite the fact that this is a precocial bird. These findings form an exception to, and hence challenge, the current rules that govern changes in relative brain size in birds. Copyright (c) 2007 S. Karger AG, Basel.

Establishing prostate cancer patient derived xenografts: Lessons learned from older studies

Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. Results Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43–46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. Conclusions Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model

Inorganic-organic composite particle as a staged delivery platform for plasmid DNA-based biopharmaceuticals

Infectious diseases such as SARS, influenza and bird flu may spread exponentially throughout communities. In fact, most infectious diseases remain major health risks due to the lack of vaccine or the lack of facilities to deliver the vaccines. Conventional vaccinations are based on damaged pathogens, live attenuated viruses and viral vectors. If the damage was not complete, the vaccination itself may cause adverse effects. Therefore, researchers have been prompted to prepare viable replacements for the attenuated vaccines that would be more effective and safer to use. DNA vaccines are generally composed of a double stranded plasmid that includes a gene encoding the target antigen under the transcriptional directory and control of a promoter region which is active in cells. Plasmid DNA (pDNA) vaccines allow the foreign genes to be expressed transiently in cells, mimicking intracellular pathogenic infection and inducing both humoral and cellular immune responses. Currently, because of their highly evolved and specialized components, viral systems are the most effective means for DNA delivery, and they achieve high efficiencies (generally >90%), for both DNA delivery and expression. As yet, viral-mediated deliveries have several limitations, including toxicity, limited DNA carrying capacity, restricted target to specific cell types, production and packing problems, and high cost. Thus, nonviral systems, particularly a synthetic DNA delivery system, are highly desirable in both research and clinical applications.

Process engineering aspects of plasmid-based biopharmaceuticals production : tackling the threatening vaccine shortages to prevent global pandemics

Infectious diseases such as SARS, influenza and bird flu have the potential to cause global pandemics; a key intervention will be vaccination. Hence, it is imperative to have in place the capacity to create vaccines against new diseases in the shortest time possible. In 2004, The Institute of Medicine asserted that the world is tottering on the verge of a colossal influenza outbreak. The institute stated that, inadequate production system for influenza vaccines is a major obstruction in the preparation towards influenza outbreaks. Because of production issues, the vaccine industry is facing financial and technological bottlenecks: In October 2004, the FDA was caught off guard by the shortage of flu vaccine, caused by a contamination in a US-based plant (Chiron Corporation), one of the only two suppliers of US flu vaccine. Due to difficulties in production and long processing times, the bulk of the world's vaccine production comes from very small number of companies compared to the number of companies producing drugs. Conventional vaccines are made of attenuated or modified forms of viruses. Relatively high and continuous doses are administered when a non-viable vaccine is used and the overall protective immunity obtained is ephemeral. The safety concerns of viral vaccines have propelled interest in creating a viable replacement that would be more effective and safer to use.

Accounting for management costs in sensitivity analyses of matrix population models

Traditional sensitivity and elasticity analyses of matrix population models have been used to inform management decisions, but they ignore the economic costs of manipulating vital rates. For example, the growth rate of a population is often most sensitive to changes in adult survival rate, but this does not mean that increasing that rate is the best option for managing the population because it may be much more expensive than other options. To explore how managers should optimize their manipulation of vital rates, we incorporated the cost of changing those rates into matrix population models. We derived analytic expressions for locations in parameter space where managers should shift between management of fecundity and survival, for the balance between fecundity and survival management at those boundaries, and for the allocation of management resources to sustain that optimal balance. For simple matrices, the optimal budget allocation can often be expressed as simple functions of vital rates and the relative costs of changing them. We applied our method to management of the Helmeted Honeyeater (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala (Phascolarctos cinereus) as examples. Our method showed that cost-efficient management of the Helmeted Honeyeater should focus on increasing fecundity via nest protection, whereas optimal koala management should focus on manipulating both fecundity and survival simultaneously. These findings are contrary to the cost-negligent recommendations of elasticity analysis, which would suggest focusing on managing survival in both cases. A further investigation of Helmeted Honeyeater management options, based on an individual-based model incorporating density dependence, spatial structure, and environmental stochasticity, confirmed that fecundity management was the most cost-effective strategy. Our results demonstrate that decisions that ignore economic factors will reduce management efficiency. ©2006 Society for Conservation Biology.

Cost-effective biodiversity restoration with uncertain growth in forest habitat quality

This paper develops a dynamic model for cost-effective selection of sites for restoring biodiversity when habitat quality develops over time and is uncertain. A safety-first decision criterion is used for ensuring a minimum level of habitats, and this is formulated in a chance-constrained programming framework. The theoretical results show; (i) inclusion of quality growth reduces overall cost for achieving a future biodiversity target from relatively early establishment of habitats, but (ii) consideration of uncertainty in growth increases total cost and delays establishment, and (iii) cost-effective trading of habitat requires exchange rate between sites that varies over time. An empirical application to the red listed umbrella species - white-backed woodpecker - shows that the total cost of achieving habitat targets specified in the Swedish recovery plan is doubled if the target is to be achieved with high reliability, and that equilibrating price on a habitat trading market differs considerably between different quality growth combinations. © 2013 Elsevier GmbH.

Costs and benefits of ivory-billed woodpecker re-discovery

Several years ago, the purported re-discovery of the ivory-billed woodpecker (Campephilus principalis) in eastern Arkansas generated lively discussion in renowned scientific journals. The debate concerned both the central question of whether the bird videotaped in April 2004 really was an ivorybilled woodpecker (eg Fitzpatrick et al. 2005; Sibley et al. 2006) and the controversy around the resulting species recovery plan and its costs (McKelvey et al. 2008; Dalton 2010): was $14 million pointlessly spent?

Paying the extinction debt: Woodland birds in the Mount Lofty Ranges, South Australia

Approximately 90% of the original woodlands of the Mount Lofty Ranges of South Australia has been cleared, modified or fragmented, most severely in the last 60 years, and affecting the avifauna dependent on native vegetation. This study identifies which woodland-dependent species are still declining in two different habitats, Pink GumBlue Gum woodland and Stringybark woodland. We analyse the Mount Lofty Ranges Woodland Bird Long-Term Monitoring Dataset for 1999-2007, to look for changes in abundance of 59 species. We use logistic regression of prevalence on lists in a Bayesian framework, and List Length Analysis to control for variation in detectability. Compared with Reporting Rate Analysis, a more traditional approach, List Length Analysis provides tighter confidence intervals by accounting for changing detectability. Several common species were declining significantly. Increasers were generally large-bodied generalists. Many birds have already disappeared from this modified and naturally isolated woodland island, and our results suggest that more specialist insectivores are likely to follow. The Mount Lofty Ranges can be regarded as a 'canary landscape' for temperate woodlands elsewhere in Australia without immediate action their bird communities are likely to follow the trajectory of the Mount Lofty Ranges avifauna. Alternatively, with extensive habitat restoration and management, we could avoid paying the extinction debt. © Royal Australasian Ornithologists Union 2011.

Regional avian species declines estimated from volunteer-collected long-term data using List Length Analysis

Long-term systematic population monitoring data sets are rare but are essential in identifying changes in species abundance. In contrast, community groups and natural history organizations have collected many species lists. These represent a large, untapped source of information on changes in abundance but are generally considered of little value. The major problem with using species lists to detect population changes is that the amount of effort used to obtain the list is often uncontrolled and usually unknown. It has been suggested that using the number of species on the list, the "list length," can be a measure of effort. This paper significantly extends the utility of Franklin's approach using Bayesian logistic regression. We demonstrate the value of List Length Analysis to model changes in species prevalence (i.e., the proportion of lists on which the species occurs) using bird lists collected by a local bird club over 40 years around Brisbane, southeast Queensland, Australia. We estimate the magnitude and certainty of change for 269 bird species and calculate the probabilities that there have been declines and increases of given magnitudes. List Length Analysis confirmed suspected species declines and increases. This method is an important complement to systematically designed intensive monitoring schemes and provides a means of utilizing data that may otherwise be deemed useless. The results of List Length Analysis can be used for targeting species of conservation concern for listing purposes or for more intensive monitoring. While Bayesian methods are not essential for List Length Analysis, they can offer more flexibility in interrogating the data and are able to provide a range of parameters that are easy to interpret and can facilitate conservation listing and prioritization. © 2010 by the Ecological Society of America.