Life-cycle preferences over consumption and health: when is cost-effectiveness analysis equivalent to cost-benefit analysis?

This paper studies life-cycle preferences over consumption and health status. We show that cost-effectiveness analysis is consistent with cost-benefit analysis if the Lifetime utility function is additive over time, multiplicative in the utility of consumption and the utility of health status, and if the utility of consumption is constant over time. We derive the conditions under which the lifetime utility function takes this form, both under expected utility theory and under rank-dependent utility theory, which is currently the most important nonexpected utility theory. If cost-effectiveness analysis is consistent with cost-benefit analysis, it is possible to derive tractable expressions for the willingness to pay for quality-adjusted life-years (QALYs). The willingness to pay for QALYs depends on wealth, remaining life expectancy, health status, and the possibilities for intertemporal substitution of consumption. (C) 1999 Elsevier Science B.V. All rights reserved.

Increased ovulation rate in Merino ewes immunized against small synthetic peptide fragments of the inhibin alpha subunit

Four experiments were carried out in Merino ewes during a period of 4 years to determine the long-term effects of immunization against different synthetic peptides mimicking the amine terminal of the or subunit of porcine inhibin. Peptides were conjugated to human serum albumin and 100-200 mu g emulsified in Freund's complete adjuvant for the primary immunization. Usually two booster injections were given at monthly intervals with 50-100 mu g conjugated peptide using either incomplete Freund's adjuvant or Montanide : Marcel. In some experiments a further immunization was carried in the next year. Blood samples were taken 10 days after each immunization, during the luteal phase, for estimation of gonadotrophin concentrations and determination of inhibin antibody titres. One day after blood sampling cloprostenol was used to induce luteolysis and laparoscopy was performed in the subsequent oestrous cycle. Immunization of ewes with synthetic peptides 1-32, 1-26, 7-26 and 8-30 resulted in large increases in the ovulation rate (OR). An approximately two-fold increase in OR was observed following the first booster immunization with these peptides and a three- to five-fold increase after the second booster immunization. Immunization with these large peptides resulted in a sustained increase in OR for a period of at least 1 year after the second booster immunization. Of the shorter peptides, peptides 10-26 and 13-26 gave a reasonable ovulatory response, although it was more difficult to obtain a response with peptides 1-16, 8-22, 13-25, 8-19 and 10-19; peptides 7-13 and 1-6 gave no response (but were examined for one breeding season only). The smaller peptides led to lower inhibin antibody titres that were not necessarily associated with increased follicle-stimulating hormone (FSH) or OR. More intensive blood sampling in one experiment showed that following primary immunization against peptide 1-32 there was a transient increase in plasma FSH which did not lead to an increased OR. Moreover, a prolonged period of raised FSH after the first booster was significantly correlated with increased OR. In these animals antibody titres were only slightly increased after primary immunization, but after the first booster immunization higher titres were observed that were significantly correlated with trough FSH values and the subsequent OR. These results are interpreted as showing that (1) to obtain an increase in OR peptides 1-32, 1-26 and 7-26 are suitable as immunogens; (2) smaller peptides are less reliable, often require multiple injections, and the response may be delayed; and (3) an extended period of raised plasma FSH is needed to give a large ovulatory response.

The last glacial cycle from the humid tropics of northeastern Australia: comparison of a terrestrial and a marine record

A detailed pollen record from the Ocean Drilling Program Site 820 core, located on the upper part of the continental slope off the coast of northeast Queensland, was constructed to compare with the existing pollen record from Lynch's Crater on the adjacent Atherton Tableland and allow the production of a regional picture of vegetation and environmental change through the last glacial cycle. Some broad similarities in patterns of vegetation change are revealed, despite the differences between sites and their pollen catchments, which can be related largely to global climate and sea-level changes. The original estimated time scale of the Lynch's Crater record is largely confirmed from comparison with the more thoroughly dated ODP record. Conversely, the Lynch's Crater pollen record has assisted in dating problematic parts of the ODP record. In contrast to Lynch's Crater, which reveals a sharp and sustained reduction in drier araucarian forest around 38,000 yrs BP, considered to have been the result of burning by Aboriginal people, the ODP record indicates, most likely, a stepwise reduction, dating from 140,000 yrs BP or beyond. The earliest reduction shows lack of a clear connection between Araucaria decline and increased burning and suggests that people may not have been involved at this stage. However, a further decline in araucarian forest, possibly around 45,000 yrs BP, which has a more substantial environmental impact and is not related to a time of major climate change, is likely, at least partially, the result of human burning. The suggestion, from the ODP core oxygen isotope record, of a regional sea-surface temperature increase of around 4 degrees C between about 400,000 and 250,000 yrs BP, may have had some influence on the overall decline in Araucaria and its replacement by sclerophyll vegetation. (C) 2000 Elsevier Science B.V. All rights reserved.

A comparison of three therapy methods for children with different types of developmental phonological disorder

Treatment case studies of three children whose speech was characterized by non-developmental errors are described. Three therapy methods were trialed with each child: phonological contrast; core vocabulary and PROMPT. The accuracy and intelligibility of the children's connected speech improved throughout: the course of the programme. Intervention that focused on teaching a rule about the contrastive use of phonemes was most successful for a child who consistently made non-developmental errors. Children making inconsistent errors received most benefit from the core vocabulary approach that markedly enhanced consistency of production. However, once consistency was established, one child benefited from phonological contrast therapy. While the results of the study should be interpreted with caution due to the small sample size and the cumulative effects of intervention, the findings suggest that different parts of a child's phonological and phonetic system may respond to various types of treatment approaches that target different aspects of speech production. The implication drawn is that just as no single treatment approach is appropriate for all children with disordered phonology, management of some children may involve selecting and sequencing a range of different approaches.

FHA domain boundaries of the Dun1p and Rad53p cell cycle checkpoint kinases

Dun1p and Rad53p of the budding yeast Saccharomyces cerevisiae are members of a conserved family of cell cycle checkpoint protein kinases that contain forkhead-associated (FHA) domains. Here, we demonstrate that these FHA domains contain 130-140 residues, and are thus considerably larger than previously predicted by sequence comparisons (55-75 residues), In vivo, expression of the proteolytically defined Dun1p FHA domain, but not a fragment containing only the predicted domain boundaries, inhibited the transcriptional induction of repair genes following replication blocks, This indicates that the non-catalytic FI-IA domain plays an important role in the transcriptional function of the Dun1p protein kinase. (C) 2000 Federation of European Biochemical Societies.

Resistance to temperature extremes between and within life cycle stages in Drosophila serrata, D-birchii and their hybrids: intraspecific and interspecific comparisons

Intraspecific Drosophila studies suggest that resistance to heal and cold stresses are largely independent and that correlations across life cycle stages are low whereas comparisons of Drosophila species indicate correlations between heat and cold resistance as well as between resistance levels in different life cycle stages. These inconsistent results may reflect differences in associations among traits at the interspecific and intraspecific levels or interspecific correlations arising because of correlated selection pressures. These alternatives were tested using Drosophila serrata, D. birchii and hybrids derived from these species. Variation among hybrid lines and families was used to test associations at the interspecific level while intraspecific variation was examined using isofemale lines of D. serrata. There was a significant association between adult heat knockdown time at 38 degreesC and adult cold resistance in one set of hybrid lines. An association between female knockdown resistance to heat and larval heat resistance was also evident in one set of hybrids. Resistance to heat anti cold at the larval stage were not correlated at either the intraspecific or interspecific levels. At the intraspecific level, lan al heat resistance and two measures of adult heat resistance were uncorrelated. Moreover, adult and larval cold resistance measures were not correlated at either the intraspecific or interspecific levels. These results suggest that there are no associations between resistance to heat and cold extremes and that extreme temperature resistance is largely independent across life cycle stages at both the intraspecific and interspecific levels. Species associations may therefore arise from correlated selection pressures rather than trait correlations. (C) 2000 The Linnean Society of London.

Synchronous oogenesis during the semilunar spawning cycle of the tropical abalone Haliotis asinina

On the southern Great Barrier Reef, Haliotis asinina (Vetigastropoda: Pleurotomarioidea) synchronously spawn every 2 wk in a predictable fashion. allowing detailed analysis of reproduction, gametogenesis, and gonad development. Histological examination of the ovaries of members of the Heron Reef population during this semilunar cycle reveals that oogenesis is also synchronous and predictable, and requires more than two spawning cycles (i.e. >28 days) to complete. Shortly after a spawning event the ovary comprises two cohorts of primary oocytes, one of which will be released at the next spawning event, and clusters of oogonia. At this time there is a rapid proliferation and expansion of trabeculae, germinal epithelial, and oogonia, and a dramatic increase in the size of the vitellogenic oocytes to be: spawned at the next spawning event. Within 4 days these oocytes have filled the ovary. On the day of the next spawning a lumen forms in the ovary as a result of localized degradation of trabeculae. The large primary oocytes dissociate from the receding trabeculae. initiate maturation, and accumulate in the lumen; these oocytes become embedded in a jelly coat layer. The next cohort of oocytes remain attached to the trabeculae. The jelly coat appears to be completely dissolved within 30 min of spawning. Comparison of the oogenesis and ovary development in II. asinina with other abalone species indicates that these processes are very similar in tropical and temperate abalone. This suggests that insights into the regulation of reproduction and spawning in H. asinina are likely to be applicable to other haliotids.

Quantification of prolactin-releasing peptide (PrRP) mRNA expression in specific brain regions of the rat during the oestrous cycle and in lactation

Real-time Taqman(TM) RT-PCR was used to make quantitative comparisons of the levels of PrRP mRNA expression in micropunch brain samples from rats at different stages of the oestrous cycle and in lactation. The nucleus of the solitary tract and ventrolateral reticular nuclei of the medulla oblongata contained significantly (P < 0.05) greater levels of PrRP mRNA than any hypothalamic region. Within the hypothalamus, the highest level of PrRP expression was localised to the dorsomedial aspect of the ventromedial hypothalamus. All other hypothalamic regions exhibited significantly (P < 0.05) lower levels of expression, including the rostral and caudal dorsomedial hypothalamus. Very low levels of PrRP expression were observed in the arcuate nucleus, paraventricular nucleus, medial preoptic nucleus and ventrolateral aspect of the ventromedial hypothalamus. No significant changes in PrRP expression were noted in any sampled region between proestrus, oestrus or dioestrus. Similarly, PrRP expression in hypothalamic regions did not differ between lactating and non-lactating (dioestrous) animals. During validation of RT-PCR techniques we cloned and sequenced a novel splice variant of PrRP from the hypothalamus. This variant arises from alternative splicing of the donor site within exon 2, resulting in an insert of 64 base pairs and shift in the-codon:reading frame with the introduction of an early stop codon. In the hypothalamus and brainstem, mRNA expression of the variant was restricted to regions that expressed PrRP. These results suggest that PrRP expression in the hypothalamus may be more Widespread than previously reported. However, the relatively low level of PrRP in the hypothalamus and the lack of significant changes in expression during the oestrous cycle and lactation provides further evidence that PrRP is unlikely to be involved in the regulation of prolactin, secretion. (C) 2003 Elsevier Science B.V. All rights reserved.

The crystal structure of free human hypoxanthineguanine phosphoribosyltransferase reveals extensive conformational plasticity throughout the catalytic cycle

Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the synthesis of the purine nucleoside monophosphates, IMP and GMP, by the addition of a 6-oxopurine base, either hypoxanthine or guanine, to the 1-beta-position of 5-phospho-U-D-ribosyl-1-pyrophosphate (PRib-PP). The mechanism is sequential, with PRib-PP binding to the free enzyme prior to the base. After the covalent reaction, pyrophosphate is released followed by the nucleoside monophosphate. A number of snapshots of the structure of this enzyme along the reaction pathway have been captured. These include the structure in the presence of the inactive purine base analogue, 7-hydroxy [4,3-d] pyrazolo pyrimidine (HPP) and PRib-PP. Mg2+, and in complex with IMP or GMP. The third structure is that of the immucillinHP.Mg2+.PPi complex, a transition-state analogue. Here, the first crystal structure of free human HGPRT is reported to 1.9 angstrom resolution, showing that significant conformational changes have to occur for the substrate(s) to bind and for catalysis to proceed. Included in these changes are relative movement of subunits within the tetramer, rotation and extension of an active-site alpha-helix (D137-D153), reorientation of key active-site residues K68, D137 and K165, and the rearrangement of three active-site loops (100-128, 165-173 and 186-196). Toxoplasina gondii HGXPRT is the only other 6-oxopurine phosphoribosyltransferase structure solved in the absence of ligands. Comparison of this structure with human HGPRT reveals significant differences in the two active sites, including the structure of the flexible loop containing K68 (human) or K79 (T gondii). (c) 2005 Elsevier Ltd. All rights reserved.