1,468 research outputs found
Cost analysis of a system of ad hoc theatre sessions for the management of delayed trauma cases
Predicting live birth, preterm and low birth weight infant after in-vitro fertilisation: a prospective study of 144018 treatment cycles
Background
The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown.
Methods and Findings
We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia.
Conclusions
Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF
Interleukin-1 polymorphisms associated with increased risk of gastric cancer
Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no
Next-to-eikonal corrections to soft gluon radiation: a diagrammatic approach
We consider the problem of soft gluon resummation for gauge theory amplitudes
and cross sections, at next-to-eikonal order, using a Feynman diagram approach.
At the amplitude level, we prove exponentiation for the set of factorizable
contributions, and construct effective Feynman rules which can be used to
compute next-to-eikonal emissions directly in the logarithm of the amplitude,
finding agreement with earlier results obtained using path-integral methods.
For cross sections, we also consider sub-eikonal corrections to the phase space
for multiple soft-gluon emissions, which contribute to next-to-eikonal
logarithms. To clarify the discussion, we examine a class of log(1 - x) terms
in the Drell-Yan cross-section up to two loops. Our results are the first steps
towards a systematic generalization of threshold resummations to
next-to-leading power in the threshold expansion.Comment: 66 pages, 19 figure
Infection with Toxoplasma gondii in a red kangaroo (Macropus rufus) and a Patagonian mara (Dolichotis patagonum) in captivity
Z' signals in polarised top-antitop final states
We study the sensitivity of top-antitop samples produced at all energy stages
of the Large Hadron Collider (LHC) to the nature of an underlying Z' boson, in
presence of full tree level standard model (SM) background effects and relative
interferences. We concentrate on differential mass spectra as well as both
spatial and spin asymmetries thereby demonstrating that exploiting combinations
of these observables will enable one to distinguish between sequential Z's and
those pertaining to Left-Right symmetric models as well as E6 inspired ones,
assuming realistic final state reconstruction efficiencies and error estimates.Comment: 21 pages, 6 colour figures, 10 table
Comparative analysis of module-based versus direct methods for reverse-engineering transcriptional regulatory networks
We have compared a recently developed module-based algorithm LeMoNe for
reverse-engineering transcriptional regulatory networks to a mutual information
based direct algorithm CLR, using benchmark expression data and databases of
known transcriptional regulatory interactions for Escherichia coli and
Saccharomyces cerevisiae. A global comparison using recall versus precision
curves hides the topologically distinct nature of the inferred networks and is
not informative about the specific subtasks for which each method is most
suited. Analysis of the degree distributions and a regulator specific
comparison show that CLR is 'regulator-centric', making true predictions for a
higher number of regulators, while LeMoNe is 'target-centric', recovering a
higher number of known targets for fewer regulators, with limited overlap in
the predicted interactions between both methods. Detailed biological examples
in E. coli and S. cerevisiae are used to illustrate these differences and to
prove that each method is able to infer parts of the network where the other
fails. Biological validation of the inferred networks cautions against
over-interpreting recall and precision values computed using incomplete
reference networks.Comment: 13 pages, 1 table, 6 figures + 6 pages supplementary information (1
table, 5 figures
NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models
INTRODUCTION:Heat shock protein 90 (HSP90) is a key component of a multichaperone complex involved in the post-translational folding of a large number of client proteins, many of which play essential roles in tumorigenesis. HSP90 has emerged in recent years as a promising new target for anticancer therapies.METHODS:The concentrations of the HSP90 inhibitor NVP-AUY922 required to reduce cell numbers by 50% (GI50 values) were established in a panel of breast cancer cell lines and patient-derived human breast tumors. To investigate the properties of the compound in vivo, the pharmacokinetic profile, antitumor effect, and dose regimen were established in a BT-474 breast cancer xenograft model. The effect on HSP90-p23 complexes, client protein degradation, and heat shock response was investigated in cell culture and breast cancer xenografts by immunohistochemistry, Western blot analysis, and immunoprecipitation.RESULTS:We show that the novel small molecule HSP90 inhibitor NVP-AUY922 potently inhibits the proliferation of human breast cancer cell lines with GI50 values in the range of 3 to 126 nM. NVP-AUY922 induced proliferative inhibition concurrent with HSP70 upregulation and client protein depletion � hallmarks of HSP90 inhibition. Intravenous acute administration of NVP-AUY922 to athymic mice (30 mg/kg) bearing subcutaneous BT-474 breast tumors resulted in drug levels in excess of 1,000 times the cellular GI50 value for about 2 days. Significant growth inhibition and good tolerability were observed when the compound was administered once per week. Therapeutic effects were concordant with changes in pharmacodynamic markers, including HSP90-p23 dissociation, decreases in ERBB2 and P-AKT, and increased HSP70 protein levels.CONCLUSION:NVP-AUY922 is a potent small molecule HSP90 inhibitor showing significant activity against breast cancer cells in cellular and in vivo settings. On the basis of its mechanism of action, preclinical activity profile, tolerability, and pharmaceutical properties, the compound recently has entered clinical phase I breast cancer trials
Risk estimates of recurrent congenital anomalies in the UK: a population-based register study
BACKGROUND: Recurrence risks for familial congenital anomalies in successive pregnancies are known, but this information for major structural anomalies is lacking. We estimated the absolute and relative risks of recurrent congenital anomaly in the second pregnancy for women with a history of a congenital anomaly in the first pregnancy; for all major anomaly groups and subtypes.
METHODS: Population-based register data on 18,605 singleton pregnancies affected by major congenital anomaly occurring in 872,493 singleton stillbirths, live births and terminations of pregnancy for fetal anomaly were obtained from the Northern Congenital Abnormality Survey, North of England, UK, for 1985-2010. Absolute risks (ARs) and relative risks (RRs) for recurrent congenital anomaly (overall, from a similar group, from a dissimilar group) in the second pregnancy were estimated by history of congenital anomaly (overall, by group, by subtype) in the first pregnancy.
RESULTS: The estimated prevalences of congenital anomaly in first and second pregnancies were 276 (95% CI 270-281) and 163 (95% CI 159-168) per 10,000 respectively. For women whose first pregnancy was affected by congenital anomaly, the AR of recurrent congenital anomaly in the second pregnancy was 408 (95% CI 365-456) per 10,000; 2.5 (95% CI 2.3-2.8, p<0.0001) times higher than for those with unaffected first pregnancies. For similar anomalies, the recurrence risk was considerably elevated (RR=23.8, 95% CI 19.6-27.9, P<0.0001) while for dissimilar anomalies the increase was more modest (RR=1.4, 95% CI 1.2-1.6, P=0.001), although the ARs for both were 2%.
CONCLUSIONS: Absolute recurrence risks varied between 1 in 20 and 1 in 30 for most major anomaly groups. At pre-conception and antenatal counselling, women whose first pregnancy was affected by a congenital anomaly and who are planning a further pregnancy may find it reassuring that despite high relative risks, the absolute recurrence risk is relatively low
Prediction of outcomes by early treatment responses in childhood T-cell acute lymphoblastic leukemia: a retrospective study in China
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