Inequalities in breast cancer reconstructive surgery according to social and locational status in Western Australia.

AIMS: To study the effects of demographic, locational and social status and the possession of private health insurance in Western Australia on the likelihood of women receiving breast reconstructive surgery after surgery for breast cancer. METHODS: The WA Record Linkage Project was used to extract all hospital morbidity, cancer and death records of women with breast cancer in Western Australia from 1982 to 2001. Comparisons between those receiving and not receiving breast reconstructive surgery were made after adjustment for co-variates in Cox regression. RESULTS: Overall, 9.1% of women received breast reconstructive surgery after surgery for breast cancer. Women who were younger, with less co-morbidity and non-indigenous women were more likely to receive breast reconstructive surgery. Women in lower socio-economic groups were much significantly less likely to receive breast reconstructive surgery (RR 0.76; 95% CI 0.54-1.06). Women from rural areas were less likely to receive breast reconstructive surgery than those from metropolitan areas (RR 0.54; 95% CI 0.25-1.15) as were those treated in a rural hospital (RR 0.78; 95% CI 0.66-0.92). Treatment in a private hospital (RR 1.25; 95% CI 1.10-1.42) or with private health insurance (RR 1.25; 95% CI 1.08-1.39) independently increased the likelihood of breast reconstructive surgery. CONCLUSION: The rate of breast reconstructive surgery was lower than expected with several factors found to affect the rate; women from disadvantaged backgrounds were less likely to receive breast reconstructive surgery than those from more privileged groups.

Acoustic hemifields in the spatial release from masking of speech by noise.

The Hearing-in-Noise Test (HINT) is able to measure the benefit to speech intelligibility in noise conferred when the noise masker is displaced 90 degrees in eccentricity from a speech source located at zero degrees azimuth. Both psychoacoustic and neurophysiological data suggest that the perceptual benefit of the 90-degree azimuth separation would be greatest if the speech and noise were presented in different acoustic hemifields, and would be smallest if the two sources were in the same acoustic hemifield. The present study tested this hypothesis directly in ten normal-hearing adult listeners. Using the HINT stimuli, we confirmed the hypothesis. Release from masking scores averaged 8.61 dB for "between-hemifield" conditions, 6.05 dB for HINT conditions, and 1.27 dB for "within-hemifield" conditions, even though all stimulus configurations retained a 90-degree angular separation of speech and noise. These data indicate that absolute separation of speech and noise alone is insufficient to guarantee a significant release from masking, and they suggest that what matters is the location of the stimulus elements relative to the left and right spatial perceptual channels.

Auditory temporal gap detection for noise markers with partially overlapping and non-overlapping spectra.

Temporal gap detection thresholds were obtained from six listeners using an adaptive tracking method and constant spectrum-level noises. In separate blocks of trials, the markers bounding the gap were systematically varied in their spectral overlap or separation (expressed in equivalent rectangular bandwidths, ERBs). In the same listeners, gap thresholds were also obtained for noises of the same bandwidths as those constituting the overlap in the overlap conditions (in the presence of a wideband notched noise masker: 'mask' conditions). For the spectral overlap/separation conditions, gap thresholds were a systematic, linear function of spectral dissimilarity in four of six listeners. In the mask conditions, gap thresholds were inversely related to bandwidth in all listeners. For the three-, four- and five-ERB conditions, gap thresholds in the same listeners for the spectral overlap conditions were higher than those for mask stimuli with the same available within-channel bandwidth and spectrum levels. These data suggest that the spectral dissimilarity between the markers over-rode the availability of within-channel information in the recovery of the temporal gap.

Central auditory onset responses, and temporal asymmetries in auditory perception.

Historically, central auditory responses have been studied for their sensitivity to various parameters of tone and noise burst stimulation, with response rate plotted as a function of the stimulus variable. The responses themselves are often quite brief, and locked in time to stimulus onset. In the stimulus amplitude domain, it has recently become clear that these responses are actually driven by properties of the stimulus' onset transient, and this has had important implications for how we interpret responses to manipulations of tone (or noise) burst plateau level. That finding was important in its own right, but a more general scrutiny of the available neurophysiological and psychophysical evidence reveals that there is a significant asymmetry in the neurophysiological and perceptual processing of stimulus onsets and offsets: sound onsets have a more elaborate neurophysiological representation, and receive a greater perceptual weighting. Hypotheses about origins of the asymmetries, derived independently from psychophysics and from neurophysiology, have in common a response threshold mechanism which adaptively tracks the ongoing level of stimulation.

A chromosomal region promoting outcrossing in a conifer.

Prefertilization mechanisms influencing selfing rates are thought to be absent in conifers. Outcrossing in conifers is promoted via an embryo-lethal system, but the genetic mechanism is poorly understood. This study is the first experimental profile of the genetic mechanism promoting outcrossing in conifers. Molecular dissection of a Pinus taeda L. selfed pedigree detected a chromosomal region identified as PtTX3020-RPtest9. Within this region, a semilethal factor was tightly linked (r = 0.0076) to a polymorphic expressed sequence tag (EST). The linkage group flanking the lethal factor showed strong heterozygote advantage. Using genotypic frequencies for the linkage group, three hypotheses about the semilethal factor could be tested: (1) the presence of a balanced lethal system, i.e., a lethal factor present in each of the two marker intervals; (2) gametic selection operative prior to fertilization; and (3) a stage-specific lethal factor. Selection acted via the embryo-lethal system. No support for a genetic mechanism operating prior to fertilization was found. The semilethal factor exerted no effect after embryo maturity. The genetic mechanism promoting outcrossing in P. taeda L. appears to have a balancing selection system due to either pseudo-overdominance or true overdominance.

Outcomes measurement for asthma following acute presentation to an emergency department.

The Asthma Management Plan (AMP) was developed by the Thoracic Society of Australia and New Zealand in 1989 to provide a more uniform approach to asthma care, aimed at reducing mortality, morbidity and emergency presentations. The AMP is often supplemented with Asthma Clinical Pathways (CPs) within the emergency department and hospital setting. This study was designed to evaluate the impact of these two instruments on asthma outcomes one month after presentation to the emergency department. The AMP and CP were both found to have had positive influences on asthma management. However, the study illustrates that there continue to be problems with asthma management, which would be improved by a more consistent use of these instruments.

Spatial and temporal factors in auditory saltation.

This report describes three experiments on auditory saltation, studied with click stimuli presented at interclick intervals (ICIs) from 30 to 240 ms. In experiment 1, subjects rated the strength of the saltation illusion evoked by trains of six monaural clicks (i.e., three presented to one ear followed by three to the other ear), and six dichotic clicks on which were imposed either a 500-micros interaural time difference or a 9-dB interaural level difference (ILD). The interaural disparity of theclicks was reversed at the midpoint of the train. Subjects reported equivalent strengths of saltation for the dichotic clicks, but weaker saltation for the monaural ones. These data indicated that saltation is supported by dichotic clicks, regardless of the stimulus manipulation used to generate the lateralized images. In experiment 2, subjects rated the strength of the saltation evoked by six click trains lateralized, in separate trials, by ILDs ranging from 9 to 30 dB, and by a train of monaural clicks. In all ILD conditions, the level of the clicks at the "quiet" ear was above click-detection threshold when presented monaurally. Saltation weakened with increasing ILD, and approximated that seen with monaural clicks when the ILD was 30 dB. These data indicated that for the range of ICIs used here, saltation weakened as the stimuli became more strongly lateralized. In experiment 3, the number of dichotic clicks preceding the disparity reversal was, in separate trials, varied from 3 to 10, and subjects were asked to detect the presence of spatial stationarity in the click train. By plotting the subjective ratings as a function of the length of the leading click train, it was shown that the temporal window within which the saltation effect operates varies between listeners, but is usually less than about 350-400 ms.

Cortisol levels predict cognitive impairment induced by electroconvulsive therapy.

BACKGROUND: Elevated glucocorticoids may increase the vulnerability of the brain to the adverse effects of repeated seizures. This study tested the hypothesis that higher ambient cortisol levels would predict increased cognitive impairment in depressed patients subsequent to receiving electroconvulsive therapy (ECT) for major depression. METHODS: Sixteen subjects provided three samples of saliva the day before receiving unilateral nondominant ECT. Measures of mood, global cognitive functioning, attention, executive function, verbal and visuospatial memory, and visuospatial processing speed were obtained 1 day before the first ECT and 1 day after the sixth ECT treatment. The relationship between basal salivary cortisol obtained before the first ECT treatment and the change score of each cognitive measure after the sixth ECT treatment was examined and tested with Pearson correlation coefficients. RESULTS: Electroconvulsive therapy treatments delivered over 2 weeks resulted in a significant improvement in mood and a decline in most measures of cognitive performance. Elevated basal cortisol was associated with a greater decline in performance of executive function, visuospatial processing speed, and verbal memory. CONCLUSIONS: Although this study is limited by the small number of subjects and the high number of comparisons, all significant correlations were consistent with the hypothesis that elevated cortisol predicts a greater degree of ECT-induced cognitive impairment.

Cytotoxic T-cell abundance and virus load in human immunodeficiency virus type 1 and human T-cell leukaemia virus type 1.

The correlation between virus load and specific cytotoxic T-lymphocyte (CTL) frequency during the chronic phase in human immunodeficiency virus type 1 (HIV-1) infection has been found to be negative in cross-sectional studies. We report here that, in infection with the related retrovirus human T-cell leukaemia virus type 1 (HTLV-1), the correlation is positive in asymptomatic carriers and zero in patients with the associated inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We demonstrate that the direction of the correlation may depend on the efficacy of the CTL response using mathematical models. We conclude that the CTL response is effective in asymptomatic carriers of HTLV-1, but ineffective in patients with HAM/TSP. Virus-mediated impairment of specific CTL production in HIV-1 infection can account for the negative correlation observed.

Sensitivity of unanesthetized chinchilla auditory system to noise burst onset, and the effects of carboplatin.

The gross near-field responses of the auditory nerve and inferior colliculus to noise burst stimuli were recorded through intracranially implanted electrodes in six unanesthetized chinchillas. Responses were studied as a function of stimulus plateau amplitude and rise time, both before and after a systemic dose of 75 mg/kg of carboplatin. Both recording sites showed sensitivity to stimulus level and rise time. Increases in stimulus level and decreases in stimulus rise time each produced increases in the response magnitude, and decreases in response latency. When the stimuli were re-specified as rate of pressure change at sound onset (Pa/s), the amplitude and latency of responses at each site were found to be a direct function of rate of sound pressure change. These data provide the first confirmation in unanesthetized animals of previous single unit observations in barbiturate-anesthetized cats. Carboplatin treatment resulted in a 20-80% loss of inner hair cells, a modest threshold elevation, and a 50-75% reduction in peak response amplitudes. The general patterns of sensitivity to stimulus level and rise time were not markedly affected by carboplatin, nor was the fashion in which response parameters (amplitude and latency) were ruled by rate of pressure change at sound onset.

Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid.

Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

Solid-phase synthesis of 1,2,3, 4-tetrahydro-beta-carboline-containing peptidomimetics.

A solid-phase method for the synthesis of 1,2,3, 4-tetrahydro-beta-carboline-containing peptidomimetics has been developed. The key step in the strategy is the Pictet-Spengler condensation of a resin-bound tryptophan-containing fragment with an Fmoc-amino aldehyde.

Production of fatty acid components of meadowfoam oil in somatic soybean embryos.

The seed oil of meadowfoam (Limnanthes alba) and other Limnanthes spp. is enriched in the unusual fatty acid Delta(5)-eicosenoic acid (20:1Delta(5)). This fatty acid has physical and chemical properties that make the seed oil of these plants useful for a number of industrial applications. An expressed sequence tag approach was used to identify cDNAs for enzymes involved in the biosynthesis of 20:1Delta(5)). By random sequencing of a library prepared from developing Limnanthes douglasii seeds, a class of cDNAs was identified that encode a homolog of acyl-coenzyme A (CoA) desaturases found in animals, fungi, and cyanobacteria. Expression of a cDNA for the L. douglasii acyl-CoA desaturase homolog in somatic soybean (Glycine max) embryos behind a strong seed-specific promoter resulted in the accumulation of Delta(5)-hexadecenoic acid to amounts of 2% to 3% (w/w) of the total fatty acids of single embryos. Delta(5)-Octadecenoic acid and 20:1Delta(5) also composed <1% (w/w) each of the total fatty acids of these embryos. In addition, cDNAs were identified from the L. douglasii expressed sequence tags that encode a homolog of fatty acid elongase 1 (FAE1), a beta-ketoacyl-CoA synthase that catalyzes the initial step of very long-chain fatty acid synthesis. Expression of the L. douglassi FAE1 homolog in somatic soybean embryos was accompanied by the accumulation of C(20) and C(22) fatty acids, principally as eicosanoic acid, to amounts of 18% (w/w) of the total fatty acids of single embryos. To partially reconstruct the biosynthetic pathway of 20:1Delta(5) in transgenic plant tissues, cDNAs for the L. douglasii acyl-CoA desaturase and FAE1 were co-expressed in somatic soybean embryos. In the resulting transgenic embryos, 20:1Delta(5) and Delta(5)-docosenoic acid composed up to 12% of the total fatty acids.

Low-copy microsatellite markers for Pinus taeda L.

Eighteen low-copy and genomic microsatellite markers were tested for Mendelian inheritance and then assayed in 41 Pinus taeda L. samples drawn from five regions in the southern United States. The PCR products had multiple alleles, high levels of polymorphism, and little non-specific priming. Fifteen of the 18 markers were informative for a P. taeda three-generation RFLP (restriction fragment length polymorphism) pedigree, and a P. taeda population survey revealed three to 28 alleles per locus. The highest allele numbers and polymorphic information content (PIC) values were associated with complex repeat sequences and (or) with sequences consisting of the longer strings of perfect repeats. The abundance of low- to rare-frequency alleles also accounted for high PIC values in both types of markers. Low-copy microsatellites are useful for the large, complex pine genome, especially in the absence of entire gene sequences in public databases and with the low levels of polymorphism in markers developed from expressed sequence tags (ESTs).

Hip fracture outcomes: quality of life and functional status in older adults living in the community.

BACKGROUND: People who return to living in the community after a hip fracture are considered to have the best outcome. However, their quality of life (QOL) and its relationship with function over the longer term have not been fully assessed. AIMS: This case control study of community dwelling subjects six to 12 months post hip fracture aims to investigate their QOL and functional independence. METHOD: The Short Form-36 (SF-36) was utilised to measure QOL. The Modified Barthel Index (MBI), the Frenchay Activities of Daily Living Index (FAI), the Timed 'Up & Go' (TUG), and the Berg Balance Scale (Berg) were used to measure functionality. RESULTS: Ninety-two subjects and 92 controls were recruited. Despite being age and gender matched, the hip fracture subjects scored significantly (p<0.05) worse than the controls in all measures of function. The fracture group was slower on the TUG (19 vs 10.5 seconds), had more difficulties with balance (46 vs 54 out of 56), and was less active and more dependent than the control group (FAI 24 vs 31 out of 42). The SF-36 has eight domains: physical function, role physical, bodily pain, mental health, role emotional, social function, general health and vitality. The control group had a higher (p<0.05) perception of their QOL in all domains. CONCLUSION: The effects of impaired balance and mobility along with reduced functional and social independence are reflected in the diminished QOL perceived by the fracture group. This indicates that many do not return to their pre-fracture lifestyle.

D-Ala-D-X ligases: evaluation of D-alanyl phosphate intermediate by MIX, PIX and rapid quench studies.

BACKGROUND: The D-alanyl-D-lactate (D-Ala-D-Lac) ligase is required for synthesis of altered peptidoglycan (PG) termini in the VanA phenotype of vancomycin-resistant enterococci (VRE), and the D-alanyl-D-serine (D-Ala-D-Ser) ligase is required for the VanC phenotype of VRE. Here we have compared these with the Escherichia coli D-Ala-D-Ala ligase DdlB for formation of the enzyme-bound D-alanyl phosphate, D-Ala(1)-PO(3)(2-) (D-Ala(1)-P), intermediate. RESULTS: The VanC2 ligase catalyzes a molecular isotope exchange (MIX) partial reaction, incorporating radioactivity from (14)C-D-Ser into D-Ala-(14)C-D-Ser at a rate of 0.7 min(-1), which approaches kinetic competence for the reversible D-Ala(1)-P formation from the back direction. A positional isotope exchange (PIX) study with the VanC2 and VanA ligases displayed a D-Ala(1)-dependent bridge to nonbridge exchange of the oxygen-18 label of [gamma-(18)O(4)]-ATP at rates of up to 0.6 min(-1); this exchange was completely suppressed by the addition of the second substrate D-Ser or D-Lac, respectively, as the D-Ala(1)-P intermediate was swept in the forward direction. As a third criterion for formation of bound D-Ala(1)-P, we conducted rapid quench studies to detect bursts of ADP formation in the first turnover of DdlB and VanA. With E. coli DdlB, there was a burst amplitude of ADP corresponding to 26-30% of the DdlB active sites, followed by the expected steady-state rate of 620-650 min(-1). For D-Ala-D-Lac and D-Ala-D-Ala synthesis by VanA, we measured a burst of 25-30% or 51% of active enzyme, respectively. CONCLUSIONS: These three approaches support the rapid (more than 1000 min(-1)), reversible formation of the enzyme intermediate D-Ala(1)-P by members of the D-Ala-D-X (where X is Ala, Ser or Lac) ligase superfamily.

1,2-Dibenzamidobenzene inhibitors of human factor Xa.

High-throughput screening of a combinatorial library of diamidophenols yielded lead compounds with the ability to inhibit human factor Xa (fXa) at micromolar concentrations (e.g. compound 4, fXa apparent K(ass) = 0.64 x 10(6) L/mol). SAR studies in this novel structural series of fXa inhibitors showed that the phenolic hydroxyl group was not essential for activity. The best activity was found in substituted 1,2-dibenzamidobenzenes in which the phenyl group of one benzoyl group (A-ring) was substituted in the 4-position with relatively small lipophilic or polarizable groups such as methoxy, vinyl, or chloro and the phenyl group of the other benzoyl group (B-ring) was substituted in the 4-position with larger lipophilic groups such as tert-butyl or dimethylamino. The central phenyl ring (C-ring) tolerated a wide variety of substituents, but methoxy, methanesulfonamido, hydroxyl, and carboxyl substitution produced slightly higher levels of activity than other substituents when present in combination with favorable B-ring substitution. Methylation of the amide nitrogen atoms was found to greatly decrease activity. Compound 12 is the highest affinity fXa inhibitor in this group of compounds, having fXa apparent K(ass) = 25.5 x 10(6) L/mol, about 40x more active than the original lead. This lead series does not show potent inhibition of human thrombin. A model for the binding of these ligands to the fXa active site is proposed. The model is consistent with the observed SAR and can serve to guide future SAR studies.

Independence of frequency channels in auditory temporal gap detection.

The ability of listeners to detect a temporal gap in a 1600-Hz-wide noiseband (target) was studied as a function of the absence and presence of concurrent stimulation by a second 1600-Hz-wide noiseband (distractor) with a nonoverlapping spectrum. Gap detection thresholds for single noisebands centered on 1.0, 2.0, 4.0, and 5.0 kHz were in the range from 4 to 6 ms, and were comparable to those described in previous studies. Gap thresholds for the same target noisebands were only modestly improved by the presence of a synchronously gated gap in a second frequency band. Gap thresholds were unaffected by the presence of a continuous distractor that was either proximate or remote from the target frequency band. Gap thresholds for the target noiseband were elevated if the distractor noiseband also contained a gap which "roved" in time in temporal proximity to the target gap. This effect was most marked in inexperienced listeners. Between-channel gap thresholds, obtained using leading and trailing markers that differed in frequency, were high in all listeners, again consistent with previous findings. The data are discussed in terms of the levels of the auditory perceptual processing stream at which the listener can voluntarily access auditory events in distinct frequency channels.