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

NHS cadet schemes: student experience, commitment, job satisfaction and job stress

In the context of various policy initiatives concerning widening access to and strengthening recruitment and retention in the health services, cadet schemes – predominantly in nursing – have proliferated over the last few years. As part of a larger national evaluation of National Health Service (NHS) cadet schemes, this paper reports on a survey of senior cadet students across 62 cadet schemes in England and examines their experience of being a cadet on such a scheme. Cadets forming the most senior cohort from each of the 62 schemes (n=596) were surveyed using a questionnaire. The questionnaire included self-rated measures of job satisfaction, job stress and commitment. A 5% sample of these cadets participated in follow-up telephone interviews. Cadets reported high satisfaction with their courses. One of the most positive aspects of the schemes was the first-hand experience of working in the NHS they provided, whilst also giving cadets the opportunity to gain recognisable skills and qualifications. Cadets scored highly on the job satisfaction scale and, on the job stress scale, showed low stress overall. A significant positive correlation was found between satisfaction and stress, indicating that the cadets who are most satisfied are also more highly stressed. A negative correlation was found between stress and the dimensions of commitment indicating that those cadets who are stressed are less committed to the NHS. A negative correlation was also found between satisfaction and the dimensions of commitment, suggesting that commitment to the NHS is not contingent on high satisfaction. The implications for the findings of the survey are discussed

Crop Updates - 2003 Weeds

This session covers Thirty four papers from different authors INTRODUCTION INTEGRATED WEED MANAGEMENT IWM system studies/demonstration sites Six years of IWM investigation – what does it tell us? Bill Roy, Agricultural Consulting and Research Services Pty Ltd Long term herbicide resistance site, the final chapter, Peter Newman and Glen Adam, Department of Agriculture Management of skeleton weed (chondrilla juncea) in a cropping rotation in Western Australia, J. R. Peirce and B. J. Rayner, Department of Agriculture WEED BIOLOGY AND COMPETITION Annual ryegrass seedbanks: The good, the bad and the ugly, Kathryn J. Steadman1, Amanda J. Ellery2 and Sally C. Peltzer3 , 1WA Herbicide Resistance Initiative, UWA, 2CSIRO Plant Industry, 3 Department of Agriculture Annual ryegrass seeds after-ripen faster during a hot summer, Kathryn J. Steadman1, Gavin P. Bignell1 and Amanda J. Ellery2, 1WA Herbicide Resistance Initiative, UWA, 2CSIRO Plant Industry Predicting annual ryegrass dormancy from climatic variables, Amanda Ellery, Andrew Moore, Sandy Nedelkos, Ross Chapman, CSIRO Plant Industry Removing dormancy in annual ryegrass seeds for early herbicide resistance testing, Kathryn J. Steadman and Mechelle J. Owen, WA Herbicide Resistance Initiative, UWA Annual ryegrass germination responds to nitrogen, Amanda Ellery1, Simone Dudley1 and Robert Gallagher2, 1CSIRO Plant Industry, 2Washington State University The agro-ecology of Malva parviflora (small flowered mallow), Pippa J. Michael, Kathryn J. Steadman and Julie A. Plummer, Western Australia Herbicide Resistance Initiative, School of Plant Biology, University of Western Australia The looming threat of wild radish, Peter Newman, Department of Agriculture IWM TOOLS Double knock, how close can we go? Peter Newman and Glen Adam, Department of Agriculture Double knock herbicide effect on annual ryegrass, Catherine Borger, Abul Hashem and Nerys Wilkins, Department of Agriculture Tactical techniques for managing Annual Ryegrass, Sally Peltzer1, Alex Douglas1, Fran Hoyle1, Paul Matson1 and Michael Walsh2 Department of Agriculture and 2Western Australian Herbicide Resistance Initiative. Weed control through soil inversion, Sally Peltzer, Alex Douglas and Paul Matson, Department of Agriculture The burning issues of annual ryegrass seed control, Darren Chitty and Michael Walsh, Western Australian Herbicide Resistance Initiative, UWA No sign of chaff-cart resistant ryegrass! David Ferris, WA Herbicide Resistance Initiative UWA PACKAGES AND MODELLING Conserving glyphosate susceptibility – modelling past, present and future us. Paul Neve1, Art Diggle2, Patrick Smith3 and Stephen Powles1 ,1Western Australian Herbicide Resistance Initiative, School of Plant Biology, University of Western Australia, 2Department of Agriculture, 3CSIRO Sustainable Ecosystems WEEDEM: A program for predicting weed emergence in Western Australia, Michael Walsh,1 David Archer2, James Eklund2 and Frank Forcella2, 1Western Australia Herbicide Resistance Initiative, UWA, 2USDA-Agricultural Research Service, 803 Iowa Avenue, Morris, MN 56267, USA Weed and herbicide management for long term profit: A workshop, Alister Draper1 and Rick Llewellyn12, 1WA Herbicide Resistance Initiative, 2School of Agricultural and Resource Economics, University of Western Australia HERBICIDE RESISTANCE Alternative herbicides for control of triazine and diflufenican multiple resistant wild radish, Aik Cheam1, Siew Lee1, David Nicholson1 and Mike Clarke2 1Department of Agriculture, Western Australia, 2Bayer CropScience Resistance of wild mustard biotype to ALS-inhibiting herbicides in WA Wheatbelt, Abul Hashem, Department of Agriculture Glyphosate-resistant ryegrass biotypes in the WA wheatbelt, Abul Hashem, Catherine Borger and Nerys Wilkins, Department of Agriculture Implications of herbicide rates for resistance management, Paul Neve, Western Australian Herbicide Resistance Initiative, University of Western Australia Putting a price on herbicide resistance, Rick Llewellyn, School of Agricultural and Resource Economics/WA Herbicide Resistance Initiative, University of Western Australia Herbicide resistance from over the fence: Mobility and management, Debbie Allena, Rick Llewellynb, aUniversity of Western Australia, 4th year student, 2002. Mingenew-Irwin Group, bSchool of Agricultural and Resource Economics/Western Australia Herbicide Resistance Initiative, University of Western Australia HERBICIDE TOLERANCE Herbicide tolerance of new barley varieties, Harmohinder S. Dhammu and Terry Piper, Department of Agriculture Herbicide tolerance of new lupins, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture Herbicide tolerance of new field pea varieties, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture Herbicide tolerance of new lentil varieties, H.S. Dhammu, T.J. Piper and L.E. Young, Department of Agriculture HERBICIDES – NEW PRODUCTS/PRODUCT USES; USE Kill half leaf ryegrass with Spray.Seed® at night, Peter Newman and Glenn Adam, Department of Agriculture CLEARFIELD™ wheat to control hard-to-kill weeds, Abul Hashem, Catherine Borger and Nerys Wilkins, Department of Agriculture Diuron, a possible alternative to simazine pre-emergent in lupins, Peter Newman and Glenn Adam, Department of Agriculture Dual Gold® soft on barley, soft on weeds in dry conditions, Peter Newman and Glenn Adam, Department of Agriculture Dual Gold® soft on lupins, soft on ryegrass in dry conditions, Peter Newman and Glenn Adam, Department of Agricultur

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Neutralization of non-vaccine human papillomavirus pseudoviruses from the A7 and A9 species groups by bivalent HPV vaccine sera

AbstractThe majority of cervical cancers are associated with infection by one or more Human Papillomavirus (HPV) types from just two distinct Alpha-Papillomavirus species groups, A7 and A9. The extent to which the current HPV16/18 vaccines will protect against other genetically related HPV types is of interest to inform vaccine implementation, cervical disease surveillance and the development of second generation HPV vaccines. The aim of this study was to determine the frequency and titer of neutralizing antibodies against a range of A7 (18, 39, 45, 59, 68) and A9 (16, 31, 33, 35, 52, 58) HPV types using sera from individuals immunized with the bivalent HPV vaccine within the school-based, UK national HPV immunization programme. Serum samples were collected from 69 girls aged 13–14 years, a median 5.9 months (inter-quartile range, IQR, 5.7–6.0) after their third vaccine dose. Cross-neutralizing antibodies against HPV31, HPV33, HPV35 and HPV45 were common and strongly associated with the titer for the related vaccine-type, but were considerably lower (<1%) than their related vaccine type-specific response. The low prevalence of these HPV types in the population and the ages within the study cohort suggest these responses are due to vaccination. It is unclear whether such low levels of neutralizing antibodies would be sufficient to protect at the site of infection in the absence of other immune effectors but the coincidence with HPV types reported from efficacy studies is intriguing. The utility of neutralizing antibodies as surrogate markers of protection remains to be determined

Comorbidity Measures In Ex Vivo T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

Abstract Clinical comorbidity measures enhance the estimates of HCT tolerance and outcomes, thereby aiding therapeutic decisions. Ex vivo T cell depletion (TCD) of the graft reduces the risk of graft-versus-host disease and improves the tolerability of allogeneic transplantation in patients with impaired pretransplant performance. However, prediction tools such as the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), have only been validated in conventional T-replete HCT. To improve outcome prediction in TCD transplants we therefore evaluated published comorbidity measures and other potential biomarkers of outcome in a series of myeloablative TCD transplant recipients. Pre transplant (week -2) factors measured were: HCT-CI, ECOG performance status, serum C-reactive protein (CRP), albumin (ALB), pre-albumin (PAB), ferritin, absolute lymphocyte counts (ALC), and absolute lymphocyte / monocyte ratio (LMR). CRP was also studied serially post transplant. CRP increased after conditioning, peaked (p =0.0001) in the first week of HCT, with recovery to baseline at 5 weeks post-HCT. We evaluated outcomes in a cohort of 79 patients in our institute with hematological malignancies receiving myeloablative total-body irradiation, and an HLA-identical sibling peripheral blood HCT, T cell depleted using Miltenyi CD34+ selection. The median age of recipients was 43 years (range 13-68 years). Of the 79, 34 (43%) had standard risk disease, and 45 (57%) recipients had high-risk disease. At a median follow up of ∼ 5 years, overall survival (OS) was 42.9% and nonrelapse mortality (NRM) was 33.9%. Comorbidity measures were first screened to eliminate highly-correlated covariates. Univariate Cox regression models were used to identify significant factors (p&lt;0.05) associated with OS and NRM (with relapse as a competing risk), which were then further evaluated by multivariable Cox regression models. In the initial analysis we eliminated pre-HCT ECOG (94% were ECOG 0) and ferritin (median 1408 mcg/L, range 11-1444), which were highly correlated (p =0.003) to the HCT-CI score (median 3, range 0-9). Similarly, ALB (median 3.9 g/L, range 2.1-5.1, p = 0.002), PAB (median 25.6 mg/dL, range 6.9-56, p =0.001) and ferritin levels (p =0.005) were excluded as highly correlated to the pre-HCT CRP (preCRP) (median 5.8 mg/L, range 0.92-96.8). CRP levels measured at 2 weeks post transplant (postCRP) (median 10.4 mg/L, range 1.9-180) and ALC (median 0.96 K/uL, range 0.02-104.6) were not correlated to the pretransplant CRP. The independent pretransplant comorbidity variables identified for further testing were HCT-CI, preCRP, post CRP, ALC and LMR. In univariable analysis of OS, significant co-variates were HCT-CI scores ≥ 5 (HR 2.09 p= 0.02), preCRP (HR=1.016, p=0.07, a trend), postCRP (HR=1.014, p&lt;0.001) and LMR ≤ 1.3 (HR=2.04, p= 0.04). In multivariable models of OS, postCRP ≥ 15 (HR 2.39, p =0.009) and LMR ≤ 1.3 (HR 2.25, p =0.04) retained significance. Confining the model to pretransplant data, then significant factors were pre CRP (HR 1.024 p= 0.02), HCT-CI≥5 (HR 2.08 p= 0.03) and LMR ≤1.3 (HR 2.43 p= 0.02). In univariable analysis of NRM, only continuous postCRP and postCRP ≥10 were significantly associated with NRM (HR=2.5, p =0.03) and in multivariable modeling of NRM, only postCRP ≥10 (HR=2.57, p=0.04) or continuous postCRP (HR=1.018, p=0.004) was found to be significant. LMR ≤ 1.3 and ECOG &gt; 0 were found to be significantly associated with the cumulative incidence of relapse (both p=0.01). In conclusion, this is the first study to explore comorbidity scores and biomarkers to predict outcome after ex vivo TCD HCT. Our results suggest that HCT-CI score, preCRP, postCRP and the LMR are important independent clinical predictors of OS and NRM in TCD HCT. Disclosures: No relevant conflicts of interest to declare. </jats:sec