Effects of intestinal spirochaete infection on egg production in meat breeders

This trial examined whether infection with intestinal spirochaetes affected egg production in female Cobb meat breeders. Infection with Serpulina pilosicoli led to delayed onset of laying and reduced egg production when compared with the control group. Egg production by birds infected with S. innocens, however, was not significantly different from that of the control group. These results suggest that infection with S. pilosicoli may be a significant cause of egg production loss in commercial birds

Global patterns in the divergence between phylogenetic diversity and species richness in terrestrial birds

Aim The conservation value of sites is often based on species richness (SR).However, metrics of phylogenetic diversity (PD) reflect a community’s evolu-tionary potential and reveal the potential for additional conservation valueabove that based purely on SR. Although PD is typically correlated with SR,localized differences in this relationship have been found in different taxa.Here, we explore geographical variation in global avian PD. We identify wherePD is higher or lower than expected (from SR) and explore correlates of thosedifferences, to find communities with high irreplaceability, in terms of theuniqueness of evolutionary histories.Location Global terrestrial.Methods Using comprehensive avian phylogenies and global distributionaldata for all extant birds, we calculated SR and Faith’s PD, a widely appliedmeasure of community PD, across the terrestrial world. We modelled the rela-tionship between avian PD for terrestrial birds and its potential environmentalcorrelates. Analyses were conducted at a global scale and also for individualbiogeographical realms. Potential explanatory variables of PD included SR,long-term climate stability, climatic diversity (using altitudinal range as aproxy), habitat diversity and proximity to neighbouring realms.Results We identified areas of high and low relative PD (rPD; PD relative tothat expected given SR). Areas of high rPD were associated with deserts andislands, while areas of low rPD were associated with historical glaciation. Ourresults suggest that rPD is correlated with different environmental variables indifferent parts of the world.Main conclusions There is geographical variation in avian rPD, much ofwhich can be explained by putative drivers. However, the importance of thesedrivers shows pronounced regional variation. Moreover, the variation in avianrPD differs substantially from patterns found for mammals and amphibians.We suggest that PD adds additional insights about the irreplaceability of com-munities to conventional metrics of biodiversity based on SR, and could beusefully included in assessments of site valuation and prioritizatio

Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the metaanalysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less fromchemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enablepatients and their clinicians to make more informed treatment choices

The diversity effect in inductive reasoning depends on sampling assumptions

A key phenomenon in inductive reasoning is the diversity effect, whereby a novel property is more likely to be generalized when it is shared by an evidence sample composed of diverse instances than a sample composed of similar instances. We outline a Bayesian model and an experimental study that show that the diversity effect depends on the assumption that samples of evidence were selected by a helpful agent (strong sampling). Inductive arguments with premises containing either diverse or nondiverse evidence samples were presented under different sampling conditions, where instructions and filler items indicated that the samples were selected intentionally (strong sampling) or randomly (weak sampling). A robust diversity effect was found under strong sampling, but was attenuated under weak sampling. As predicted by our Bayesian model, the largest effect of sampling was on arguments with nondiverse evidence, where strong sampling led to more restricted generalization than weak sampling. These results show that the characteristics of evidence that are deemed relevant to an inductive reasoning problem depend on beliefs about how the evidence was generated.Brett K. Hayes, Danielle J. Navarro, Rachel G. Stephens, Keith Ransom, Natali Dilevsk

Developing pathways to clarify pathogenicity of unclassified variants in osteogenesis imperfecta genetic analysis

Background With increased access to genetic testing, variants of uncertain significance (VUS) where pathogenicity is uncertain are being increasingly identified. More than 85% Osteogenesis Imperfecta (OI) patients have pathogenic variants in COL1A1/A2. However, when a VUS is identified, there are no pathways in place for determining significance. Objective Define a diagnostic pathway to confirm pathogenicity, providing patients with definitive genetic diagnosis, accurate recurrence risks, and prenatal testing options. Methods Functional studies on collagen secretion from cultured patient fibroblasts combined with detailed phenotyping and segregation family studies. Results We demonstrate data from a family with a VUS identified in type I collagen. Family‐1 Six‐year‐old boy with failure‐to‐gain weight, talipes, fractures, on and off treatment with Pamidronate as diagnosis of OI uncertain. Transiliac bone biopsy at 2 years of age demonstrated active new bone formation within periosteum; bone cortices were normal thickness but increased porosity. Trabecular bone showed features of advanced osteoporosis. Genetic testing identified a de novo COL1A1 c.206_208delTGT, p.Leu69del variant. Sibling with similar phenotype but no fractures as yet, tested positive for variant raising concerns regarding her diagnosis, and management. Results from three independent experiments (cell immunofluorescence, collagen secretion assay by Western Blot, and unbiased proteomics) from cultured patient fibroblasts demonstrate COL1A1 c.206_208delTGT, p.Leu69del variant causing a substantial defect to collagen extracellular matrix assembly confirming variant pathogenicity. Conclusion Access to genetic testing in OI is increasing as advances in genetic technologies decreases cost; a clinical diagnostic pathway needs to be implemented for managing variants identified by such testing

Noise Kernel and Stress Energy Bi-Tensor of Quantum Fields in Hot Flat Space and Gaussian Approximation in the Optical Schwarzschild Metric

Continuing our investigation of the regularization of the noise kernel in curved spacetimes [N. G. Phillips and B. L. Hu, Phys. Rev. D {\bf 63}, 104001 (2001)] we adopt the modified point separation scheme for the class of optical spacetimes using the Gaussian approximation for the Green functions a la Bekenstein-Parker-Page. In the first example we derive the regularized noise kernel for a thermal field in flat space. It is useful for black hole nucleation considerations. In the second example of an optical Schwarzschild spacetime we obtain a finite expression for the noise kernel at the horizon and recover the hot flat space result at infinity. Knowledge of the noise kernel is essential for studying issues related to black hole horizon fluctuations and Hawking radiation backreaction. We show that the Gaussian approximated Green function which works surprisingly well for the stress tensor at the Schwarzschild horizon produces significant error in the noise kernel there. We identify the failure as occurring at the fourth covariant derivative order.Comment: 21 pages, RevTeX

Stochastic Production Of Kink-Antikink Pairs In The Presence Of An Oscillating Background

We numerically investigate the production of kink-antikink pairs in a $(1+1)$ dimensional $\phi^4$ field theory subject to white noise and periodic driving. The twin effects of noise and periodic driving acting in conjunction lead to considerable enhancement in the kink density compared to the thermal equilibrium value, for low dissipation coefficients and for a specific range of frequencies of the oscillating background. The dependence of the kink-density on the temperature of the heat bath, the amplitude of the oscillating background and value of the dissipation coefficient is also investigated. An interesting feature of our result is that kink-antikink production occurs even though the system always remains in the broken symmetry phase.Comment: Revtex, 21 pages including 7 figures; more references adde

Effective killing of the human pathogen Candida albicans by a specific inhibitor of non-essential mitotic kinesin Kip1p

Kinesins from the bipolar (Kinesin-5) family are conserved in eukaryotic organisms and play critical roles during the earliest stages of mitosis to mediate spindle pole body separation and formation of a bipolar mitotic spindle. To date, genes encoding bipolar kinesins have been reported to be essential in all organisms studied. We report the characterization of CaKip1p, the sole member of this family in the human pathogenic yeast Candida albicans. C. albicans Kip1p appears to localize to the mitotic spindle and loss of CaKip1p function interferes with normal progression through mitosis. Inducible excision of CaKIP1 revealed phenotypes unique to C. albicans, including viable homozygous Cakip1 mutants and an aberrant spindle morphology in which multiple spindle poles accumulate in close proximity to each other. Expression of the C. albicans Kip1 motor domain in Escherichia coli produced a protein with microtubule-stimulated ATPase activity that was inhibited by an aminobenzothiazole (ABT) compound in an ATP-competitive fashion. This inhibition results in ‘rigor-like’, tight association with microtubules in vitro. Upon treatment of C. albicans cells with the ABT compound, cells were killed, and terminal phenotype analysis revealed an aberrant spindle morphology similar to that induced by loss of the CaKIP1 gene. The ABT compound discovered is the first example of a fungal spindle inhibitor targeted to a mitotic kinesin. Our results also show that the non-essential nature and implementation of the bipolar motor in C. albicans differs from that seen in other organisms, and suggest that inhibitors of a non-essential mitotic kinesin may offer promise as cidal agents for antifungal drug discovery

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.