Introduction

This is the post print version of the chapter - Copyright @ 2003 The editorsThis book is about surrogacy and, more specifically, surrogate motherhood. It is a collection of essays that aims to provide a contemporary and international picture of a practice, traceable to ancient times, devised to solve the problem of childlessness. The collection, which explores surrogacy from a variety of perspectives including law, policy, medicine and psychology, is timely. For although there is nothing new in the notion that a woman might bear a child for someone else, there is some evidence that the incidence of surrogacy is increasing and technology has developed to make ever more complex arrangements possible

Sex steroid hormones in relation to Barrett’s esophagus: An analysis of the FINBAR Study

Previously we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g., estrone + estradiol OR(continuous per ½ IQR)=2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g., free testosterone OR(continuous per ½ IQR)=2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis

Ascertainment of occupational histories in the working population: The occupational history calendar approach

Background Self-reported occupational histories are an important means for collecting historical data in epidemiological studies. An occupational history calendar (OHC) has been developed for use alongside a national occupational hazard surveillance tool. This study presents the systematic development of the OHC and compares work histories collected via this calendar to those collected via a traditional questionnaire. Methods The paper describes the systematic development of an OHC for use in the general working population. A comparison of data quality and recall was undertaken in 51 participants where both tools were administered. Results TheOHCenhanced job recall compared with the traditional questionnaire. Good agreement in the data captured by both tools was observed, with the exception of hazard exposures. Conclusions A calendar approach is suitable for collecting occupational histories from the general working population. Despite enhancing job recall the OHC approach has some shortcomings outweighing this advantage in large-scale population surveillance

A randomized trial of glutamine and antioxidants in critically ill patients.

BACKGROUND: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting. METHODS: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance. RESULTS: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83). CONCLUSIONS: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.)

Appropriate design and reporting of superiority, equivalence and non-inferiority clinical trials incorporating a benefit risk assessment: the BRAINS study including expert workshop

Background Randomised controlled trials are designed to assess the superiority, equivalence or non-inferiority of a new health technology, but which trial design should be used is not always obvious in practice. In particular, when using equivalence or non-inferiority designs, multiple outcomes of interest may be important for the success of a trial, despite the fact that usually only a single primary outcome is used to design the trial. Benefit–risk methods are used in the regulatory clinical trial setting to assess multiple outcomes and consider the trade-off of the benefits against the risks, but are not regularly implemented in publicly funded trials. Objectives The aim of the project is to aid the design of clinical trials with multiple outcomes of interest by defining when each trial design is appropriate to use and identifying when to use benefit–risk methods to assess outcome trade-offs (qualitatively or quantitatively) in a publicly funded trial setting. Methods A range of methods was used to elicit expert opinion to answer the project objectives, including a web-based survey of relevant researchers, a rapid review of current literature and a 2-day consensus workshop of experts (in 2019). Results We created a list of 19 factors to aid researchers in selecting the most appropriate trial design, containing the following overarching sections: population, intervention, comparator, outcomes, feasibility and perspectives. Six key reasons that indicate a benefit–risk method should be considered within a trial were identified: (1) when the success of the trial depends on more than one outcome; (2) when important outcomes within the trial are in competing directions (i.e. a health technology is better for one outcome, but worse for another); (3) to allow patient preferences to be included and directly influence trial results; (4) to provide transparency on subjective recommendations from a trial; (5) to provide consistency in the approach to presenting results from a trial; and (6) to synthesise multiple outcomes into a single metric. Further information was provided to support the use of benefit–risk methods in appropriate circumstances, including the following: methods identified from the review were collated into different groupings and described to aid the selection of a method; potential implementation of methods throughout the trial process were provided and discussed (with examples); and general considerations were described for those using benefit–risk methods. Finally, a checklist of five pieces of information that should be present when reporting benefit–risk methods was defined, with two additional items specifically for reporting the results. Conclusions These recommendations will assist research teams in selecting which trial design to use and deciding whether or not a benefit–risk method could be included to ensure research questions are answered appropriately. Additional information is provided to support consistent use and clear reporting of benefit–risk methods in the future. The recommendations can also be used by funding committees to confirm that appropriate considerations of the trial design have been made. Limitations This research was limited in scope and should be considered in conjunction with other trial design methodologies to assess appropriateness. In addition, further research is needed to provide concrete information about which benefit–risk methods are best to use in publicly funded trials, along with recommendations that are specific to each method

Synthetic strategies for preparing BEDT-TTF derivatives functionalised with metal ion binding groups

The syntheses of BEDT-TTF (ET) derivatives with potential metal ion binding pyridyl, bipyridyl and terpyridyl groups are achieved either by stepwise construction of the organosulfur core or via reactions of hydroxymethyl-ET for which a cheap and efficient four step route is reported. The tosylate of hydroxymethyl-ET, reported for the first time, undergoes nucleophilic substitutions with pyridyl, bipyridyl- and terpyridyl-thiolates to give new donors. The X-ray crystal structures of two substituted ET derivatives show considerable deviation of the organosulfur donor system from planarity by bending about the short molecular axis of the ET group

Canopy nitrogen, carbon assimilation, and albedo in temperate and boreal forests: Functional relations and potential climate feedbacks

The availability of nitrogen represents a key constraint on carbon cycling in terrestrial ecosystems, and it is largely in this capacity that the role of N in the Earth\u27s climate system has been considered. Despite this, few studies have included continuous variation in plant N status as a driver of broad-scale carbon cycle analyses. This is partly because of uncertainties in how leaf-level physiological relationships scale to whole ecosystems and because methods for regional to continental detection of plant N concentrations have yet to be developed. Here, we show that ecosystem CO2 uptake capacity in temperate and boreal forests scales directly with whole-canopy N concentrations, mirroring a leaf-level trend that has been observed for woody plants worldwide. We further show that both CO2 uptake capacity and canopy N concentration are strongly and positively correlated with shortwave surface albedo. These results suggest that N plays an additional, and overlooked, role in the climate system via its influence on vegetation reflectivity and shortwave surface energy exchange. We also demonstrate that much of the spatial variation in canopy N can be detected by using broad-band satellite sensors, offering a means through which these findings can be applied toward improved application of coupled carbon cycle–climate models