TOLERANCE INTERVALS FOR GENE FLOW RATES FROM TRANSGENIC TO NON-TRANSGENIC WHEAT AND CORN USING A LOGISTIC REGRESSION MODEL WITH RANDOM LOCATION EFFECTS

Crop scientists and government regulators are interested in mediating pollen flow from transgenic crops to other crops and weed species. To this end, a multi-year, multilocation series of experiments was conducted in eastern Colorado by the Department of Soil and Crop Sciences at Colorado State University. These experiments were done to estimate the distance required between plots of transgenic corn and wheat and plots of the respective non-transgenic crop to obtain at most a regulated limit of cross-pollination. The experiments involved planting a rectangle of transgenic crop in the middle of a non-transgenic field and measuring the proportion of cross-pollinated crop at various distances along transects radiating in multiple directions. Gene flow to the non-transgenic crop was evaluated in wheat using herbicide tolerance and in corn using kernel color. An initial Generalized Linear Mixed Model with binomial response and logit link was estimated with independent variables: a square root transformation of distance, an additional covariate, and a random location effect. For corn, the additional covariate was transect orientation; for wheat, it was the relative heading time of the recipient variety. An enhanced model that included additional sources of variation was also examined. The analysis for both of these assumed models addresses two problems: 1) an Upper Tolerance Limit on the binomial probability of cross-pollination, which includes 100c% of the locations with 100d% confidence, at set values of the independent variables; and 2) an Upper Tolerance Limit on the distance at which 100c% of the locations will have binomial probability of cross-pollination less than a specified value, with 100d% confidence, at set values of the other independent variables. The problems are addressed using Frequentist and Bayesian methods

Health Impact Assessment in New South Wales & Health in All Policies in South Australia: differences, similarities and connections

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Policy decisions made within all sectors have the potential to influence population health and equity. Recognition of this provides impetus for the health sector to engage with other sectors to facilitate the development of policies that recognise, and aim to improve, population outcomes. This paper compares the approaches implemented to facilitate such engagement in two Australian jurisdictions. These are Health Impact Assessment (HIA) in New South Wales (NSW) and Health in All Policies (HiAP) in South Australia (SA). Methods: The comparisons presented in this paper emerged through collaborative activities between stakeholders in both jurisdictions, including critical reflection on HIA and HiAP practice, joint participation in a workshop, and the preparation of a discussion paper written to inform a conference plenary session. The plenary provided an opportunity for the incorporation of additional insights from policy practitioners and academics. Results: Comparison of the approaches indicates that their overall intent is similar. Differences exist, however, in the underpinning principles, technical processes and tactical strategies applied. These differences appear to stem mainly from the organisational positioning of the work in each state and the extent to which each approach is linked to government systems. Conclusions: The alignment of the HiAP approach with the systems of the SA Government increases the likelihood of influence within the policy cycle. However, the political priorities and sensitivities of the SA Government limit the scope of HiAP work. The implementation of the HIA approach from outside government in NSW means greater freedom to collaborate with a range of partners and to assess policy issues in any area, regardless of government priorities. However, the comparative distance of HIA from NSW Government systems may reduce the potential for impact on government policy. The diversity in the technical and tactical strategies that are applied within each approach provides insight into how the approaches have been tailored to suit the particular contexts in which they have been implemented. Keywords: Health in all policies, Health impact assessment, Healthy public polic

Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II):a randomised trial

SummaryBackgroundThe balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10–100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients.MethodsIn this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967.Findings307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI −4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367).InterpretationThe STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage.FundingUK Medical Research Council

T-replete cord transplants give superior outcomes in high risk and relapsed/refractory paediatric myeloid malignancy

Stem cell transplant (SCT) outcomes in high-risk (HR) and relapsed/refractory (R/R) paediatric acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) have been poor historically. Cord blood allows T-cell replete transplant (TRCB), enabling enhanced graft-versus-leukaemia. We collected data from 367 consecutive patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for paediatric AML/MDS in the UK and Ireland between January 2014 and December 2021. Data was collected about patient's demographics, disease and its treatment including previous transplant, measurable residual disease (MRD) status at transplant, HLA-match, relapse, death, graft versus host disease (GvHD) and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6% and 5.1% respectively in the comparator group (all p <0.001). Within the TRCB cohort, Event Free Survival (EFS) was 64.1%, 50% in MRD positive patients and 79% in MRD negative (p= 0.009). To allow for the imbalance in baseline characteristics, a multivariable analysis was performed: the TRCB cohort had significantly improved EFS (0.57[0.35-0.91], p=0.019), time to relapse (0.46[0.26-0.81), p=0.008), and reduced chronic GVHD (HR 0.28 [95% CI 0.11-0.70]; p=0.007), with some evidence of improved Overall Survival (OS) (0.65[0.39-1.07], p = 0.088). The effect appeared similar regardless of MRD status, (interaction p-value= 0.29). CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy

Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II) Protocol

<p>Abstract</p> <p>Background</p> <p>Within the spectrum of spontaneous intracerebral haemorrhage there are some patients with large or space occupying haemorrhage who require surgery for neurological deterioration and others with small haematomas who should be managed conservatively. There is equipoise about the management of patients between these two extremes. In particular there is some evidence that patients with lobar haematomas and no intraventricular haemorrhage might benefit from haematoma evacuation. The STICH II study will establish whether a policy of earlier surgical evacuation of the haematoma in selected patients will improve outcome compared to a policy of initial conservative treatment.</p> <p>Methods/Design</p> <p>an international multicentre randomised parallel group trial. Only patients for whom the treating neurosurgeon is in equipoise about the benefits of early craniotomy compared to initial conservative treatment are eligible. All patients must have a CT scan confirming spontaneous lobar intracerebral haemorrhage (≤1 cm from the cortex surface of the brain and 10-100 ml in volume). Any clotting or coagulation problems must be corrected and randomisation must take place within 48 hours of ictus. With 600 patients, the study will be able to demonstrate a 12% benefit from surgery (2p < 0.05) with 80% power.</p> <p>Stratified randomisation is undertaken using a central 24 hour randomisation service accessed by telephone or web. Patients randomised to early surgery should have the operation within 12 hours. Information about the status (Glasgow Coma Score and focal signs) of all patients through the first five days of their trial progress is also collected in addition to another CT scan at about five days (+/- 2 days). Outcome is measured at six months via a postal questionnaire to the patient. Primary outcome is death or severe disability defined using a prognosis based 8 point Glasgow Outcome Scale. Secondary outcomes include: Mortality, Rankin, Barthel, EuroQol, and Survival.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN22153967">ISRCTN22153967</a></p