High-throughput phenotyping (HTP) identifies seedling root traits linked to variation in seed yield and nutrient capture in field-grown oilseed rape (Brassica napus L.).

Background and Aims Root traits can be selected for crop improvement. Techniques such as soil excavations can be used to screen root traits in the field, but are limited to genotypes that are well-adapted to field conditions. The aim of this study was to compare a low-cost, high-throughput root phenotyping (HTP) technique in a controlled environment with field performance, using oilseed rape (OSR; Brassica napus) varieties. Methods Primary root length (PRL), lateral root length and lateral root density (LRD) were measured on 14-d-old seedlings of elite OSR varieties (n = 32) using a 'pouch and wick' HTP system (∼40 replicates). Six field experiments were conducted using the same varieties at two UK sites each year for 3 years. Plants were excavated at the 6- to 8-leaf stage for general vigour assessments of roots and shoots in all six experiments, and final seed yield was determined. Leaves were sampled for mineral composition from one of the field experiments. Key Results Seedling PRL in the HTP system correlated with seed yield in four out of six (r = 0·50, 0·50, 0·33, 0·49; P < 0·05) and with emergence in three out of five (r = 0·59, 0·22, 0·49; P < 0·05) field experiments. Seedling LRD correlated positively with leaf concentrations of some minerals, e.g. calcium (r = 0·46; P < 0·01) and zinc (r = 0·58; P < 0·001), but did not correlate with emergence, general early vigour or yield in the field. Conclusions Associations between PRL and field performance are generally related to early vigour. These root traits might therefore be of limited additional selection value, given that vigour can be measured easily on shoots/canopies. In contrast, LRD cannot be assessed easily in the field and, if LRD can improve nutrient uptake, then it may be possible to use HTP systems to screen this trait in both elite and more genetically diverse, non-field-adapted OSR.

The development and evaluation of options for improving future U.K. blood component labelling--outcome of the 2013 U.K. hospital survey.

BACKGROUND/OBJECTIVES: U.K. blood component labels have evolved to accommodate a plethora of information. Concern has, however, been expressed that current U.K. labelling is too 'cluttered', detracting from the clarity of critical information. This prompted a holistic review of labelling and available information technology (IT) with the aim of improving the situation. METHODS/MATERIALS: A survey was circulated requiring U.K. hospital participants to rank each item of information on the label according to its 'criticality' and assess three novel 'future' and one 'transition' prototype labels. Prototypes were based on applicable regulatory standards, best practice guidance, international benchmark data and U.K. expert input. The prototypes support steps towards 'full face' label printing and utilise 2D and quick response (QR) barcodes. RESULTS: Two-hundred eleven completed surveys were received identifying 110 contributing hospitals with 41% from clinical staff, 37% from transfusion laboratory staff and 22% from transfusion practitioners. There was excellent agreement between the three groups on the critical information, i.e., blood group, expiry date, blood component name, unique donation identification number (DIN) and blood component volume but far less on the other information, especially the various warning messages. Of the 'future' labels, option 3 (closest to the current 'quadrant model') was most popular. Option 1, with its additional inverted section replicating critical information was least popular and prompted significant safety concerns. CONCLUSION: The prototype labels correctly identified the critical items of information and extensive comments confirmed that this was more prominently and clearly displayed. Laboratory staff commented that the transition label was essential to enable IT systems to be adapted.

Ensuring that blood transfusion sets administer an effective dose of functional blood components.

BACKGROUND: Proposed changes to ISO 1135-4 will require that blood transfusion administration sets are demonstrated by the manufacturers to be suitable for the range of cellular and plasma blood components for which they are designated. AIMS: To design a test protocol to asses the depletion of the blood components by transfusion sets and damage and activation of blood components during their passage through the set. METHODS: Transfusion giving sets (CareFusion Ref no. 60895 180311 and Fresenius Ref no. 2900032) were assessed by comparing samples of the blood component taken prior to and after passage through the transfusion set in strict accordance with the manufacturer's instructions. As well as depletion of red cells, platelets and FVIIIc, the following markers of damage/activation were assessed: red cells-supernatant haemolysis and potassium; FFP-prothrombin fragments 1 and 2 and fibrinopeptide A and platelets-pH, CD62P, CD63 and sP-selectin. RESULTS: The CareFusion and the Fresenius transfusion sets gave less than 5% depletion of blood components and caused negligible and clinically insignificant effects on red cells, platelet concentrates and FFP. CONCLUSION: A practical test protocol has been established to assess the depletion, damage to and activation of the key constituents of commonly requested blood components. This protocol would provide a valuable addition to ISO 1135-4 in assuring the suitability of transfusion sets.

The donor line break cannula: effect on the donation process, blood component quality and transfusion microbiology testing of an important new blood bag safety feature.

BACKGROUND: The use of blood packs with an integral sampling system can result in anti-coagulant from the main bag reaching the sample pouch via the donor line, causing delayed coagulation of blood samples. In NHS Blood and Transplant, this has prevented the use of serum, the preferred matrix for transfusion microbiology (TM) testing, which has led to an increased false positive rate with ethylenediaminetetraacetic acid (EDTA) plasma. There is also a remote possibility of false negative results owing to sample dilution. Manufacturers have responded by offering packs with a donor line break cannula (DLBC) to prevent these adverse effects. OBJECTIVES: The aims of this study were to assess the impact of DLBC packs on donation, blood component quality and of the potential return to serum for TM testing. METHODS: DLBC packs from three manufacturers were assessed against control packs of the same dimensions and configuration. Donation duration, flow rate, platelet factor 4, prothrombin fragment 1+2, haemolysis and collection and processing incidents were compared. RESULTS: Results indicated no clinically significant adverse effect from the DLBC on the activation state of platelets, the coagulation cascade or increased haemolysis. Donation duration and blood collection and processing incident rates for DLBC packs were not significantly different to controls. CONCLUSIONS: The use of DLBC packs would reduce the complexity of manipulations during blood collection and therefore the likelihood of microbially contaminated donations (incorrect skin core diversion) and false negative TM tests. DLBC packs would enable the use of serum for TM testing with a significant reduction in false positive tests compared to EDTA plasma.

Semistochastic projector Monte Carlo method.

We introduce a semistochastic implementation of the power method to compute, for very large matrices, the dominant eigenvalue and expectation values involving the corresponding eigenvector. The method is semistochastic in that the matrix multiplication is partially implemented numerically exactly and partially stochastically with respect to expectation values only. Compared to a fully stochastic method, the semistochastic approach significantly reduces the computational time required to obtain the eigenvalue to a specified statistical uncertainty. This is demonstrated by the application of the semistochastic quantum Monte Carlo method to systems with a sign problem: the fermion Hubbard model and the carbon dimer.

An evaluation of statistical process control techniques applied to blood component quality monitoring with particular reference to CUSUM.

BACKGROUND: Statistical process control (SPC) is used to monitor the performance of blood component collection and production processes in the UK and elsewhere. The sensitivity of the applied technique(s) needs to be matched to the clinical importance of the parameter being monitored such that significant deviations in the process mean and/or variability of critical parameters (e.g. the leucocyte content of leucodepleted components) are detected and investigated immediately. AIMS: This study assessed the sensitivity and specificity of a range of techniques for variable and attribute (proportion non-conforming) data. MATERIALS AND METHODS: Comparison was based on a range of simulated and 'live' blood component quality monitoring data including X/R, cumulative sum (CUSUM) procedures, the scan statistic and np charts. RESULTS: X/R and CUSUM could detect shifts of two standard deviations in the process mean within 5 days. Current leucocyte count data (substantially skewed even after log transformation) was found to be better suited to attribute analysis. CUSUM alone was able to detect shifts on the same day when based on 20 or more samples and achieved acceptable specificity. CONCLUSIONS: CUSUM procedures for proportion non-conforming can usefully augment existing X/R techniques for leucodepletion monitoring, provide valid control limits and the required sensitivity. The scan statistic and 'np' charts offered no obvious advantages.

Minimally invasive surgery for neuroblastic tumours: A SIOPEN multicentre study: Proposal for guidelines.

INTRODUCTION: Surgery plays a key role in the management of Neuroblastic tumours (NB), where the standard approach is open surgery, while minimally invasive surgery (MIS) may be considered an option in selected cases. The indication(s) and morbidity of MIS remain undetermined due to small number of reported studies. The aim of this study was to critically address the contemporary indications, morbidity and overall survival (OS) and propose guidelines exploring the utility of MIS for NB. MATERIALS & METHODS: A SIOPEN study where data of patients with NB who underwent MIS between 2005 and 2018, including demographics, tumour features, imaging, complications, follow up and survival, were extracted and then analysed. RESULTS: A total of 222 patients from 16 centres were identified. The majority were adrenal gland origin (54%) compared to abdominal non-adrenal and pelvic (16%) and thoracic (30%). Complete and near complete macroscopic resection (>95%) was achieved in 95%, with 10% of cases having conversion to open surgery. Complications were reported in 10% within 30 days of surgery. The presence of IDRF (30%) and/or tumour volume >75 ml were risk factors for conversion and complications in multivariate analysis. Overall mortality was 8.5%. CONCLUSIONS: MIS for NB showed that it is a secure approach allowing more than 95% resection. The presence of IDRFs was not an absolute contraindication for MIS. Conversion to open surgery and overall complication rates were low, however they become significant if tumour volume >75 mL. Based on these data, we propose new MIS guidelines for neuroblastic tumours.

Eurobloodpack: a common European design for blood bag systems with integral leucodepletion filters.

Three EBA specified blood bag configurations ('Eurobloodpack') are described which are capable of meeting >80% of its member's requirements. These include a 'top-and-top' and two 'bottom-and-top' packs enabling aseptic, pre-donation collection of up to 40 ml of samples, 427.5-522.5 ml of whole blood and the preparation of an extensive range of blood components. Features currently beyond the scope of ISO standardisation have been controlled including: anticoagulant and additive volumes; collection needle and sampling system; transfer tubing; cross-match line; base label; leucodepletion filter performance; compatibility of access ports and transfusion sets. Eurobloodpack has significant advantages for blood services and blood bag manufacturers.

Current uses of transfusion administration sets: a cause for concern?

There is potential for inappropriate use of transfusion administration sets when used in combination with modern infusion pumps with consequences for patient safety. The aims of our study were to (i) establish if the design and testing of transfusion sets specified in International Standard ISO 1135-4 are adequate for their current applications, (ii) identify if infusion pumps currently supplied in the UK for blood component administration are suitable for this purpose and (iii) determine the additional control measures needed to be applied by manufacturers and users to ensure patient safety. Keyword literature search was carried out to review and correlate important transfusion parameters with resultant adverse effects. Units for occlusion pressure, flow rate and haemolysis were standardised for ease of comparison. A sample of transfusion set instructions for use was reviewed. Principal suppliers of infusion pumps to the UK market were surveyed to identify those sold for blood transfusion, their recommended operating parameters and compatible transfusion sets. Previous work showed clinically unacceptable haemolysis at pressures above 40 kPa. Modern infusion pumps operate under negative pressures of up to 210 kPa. ISO 1135-4 design and test requirements do not match this performance and in particular omit testing under negative pressure. Transfusion sets surveyed did not indicate flow or pressure restrictions or specify the blood components with which they had been validated. ISO 1135-4 requires updating and has been initiated. Meanwhile, recommendations are made for transfusion set manufacturers concerning pressure limitations and restrictions on blood component type and for users concerning purchase, configuration and validation of infusion pumps and disposables.

Tracing nitrate sources with a combined isotope approach (δ15NNO3, δ18ONO3 and δ11B) in a large mixed-use watershed in southern Alberta, Canada.

Rapid population growth and land-use intensification over the last century have resulted in a substantial increase in nutrient loads degrading marine and freshwater ecosystems worldwide. In mixed-use watersheds, elevated nitrogen loads from wastewater treatment plant (WWTP) effluent or agricultural runoff often drive the eutrophication of waterways. Accordingly, the objective of this research was to identify sources of riverine nitrate (NO3), a deleterious dissolved species of nitrogen, with a combined isotopic tracing technique in the Bow River and the Oldman River in Alberta, Canada. Riverine NO3 and boron (B) concentrations, mean daily flux and δ15NNO3, δ18ONO3, and δ11B values were determined at 17 mainstem sites during high and low discharge periods in 2014 and 2015. The data for mainstem sites were then compared to results for effluent from seven WWTPs, eight synthetic fertilizers, cow manure, and three predominantly agricultural tributary sites to estimate point and non-point NO3 sources. The NO3 flux, δ15NNO3 and δ18ONO3 values indicated the city of Calgary's Bonnybrook WWTP effluent accounts for the majority of the NO3 flux in the Bow River downstream of Calgary. δ15NNO3 and δ11B values in the Bow River highlighted an increase in agricultural NO3 loading downstream of irrigation return-flows. A three-fold decrease in the NO3:B flux ratio indicated NO3-removal processes are active in the lower reaches of the Bow River. For the Oldman River, δ11B values revealed elevated nutrient loading from the Lethbridge WWTP effluent (10% of downstream B flux). Furthermore, the agricultural tributaries contributed 25% of the local B flux to the Oldman River. Overall, δ11B was proven to be an effective co-tracer for discriminating between urban and agricultural sources of NO3 in these large mixed-use watersheds. This combined isotope tracing approach has significant potential to identify point and non-point NO3 sources driving eutrophication around the world.

Practical guidelines for applying statistical process control to blood component production.

Legislation, guidelines and recommendations for blood components related to statistical process control (SPC) and the selection of a quality monitoring (QM) sampling regimen are subject to misinterpretation and lack practical guidance on implementation. The aim of this article is: to review and interpret applicable European legislation and guidelines and to develop an SPC strategy that meets these requirements; and to provide practical guidance on the selection and application of appropriate techniques and the interpretation of resultant blood component QM data. A methodology is presented which utilizes: an algorithm to select an appropriate quality-monitoring strategy for the blood component parameter under consideration; a range of straightforward, validated SPC techniques for variable data and an assessment of process capability (Cpk) and blood component parameter 'criticality' to determine the sampling regimen. The methodology was applied to routine National Health Service Blood and Transplant (NHSBT) blood component data for 2005-2006. Cpk values ranged from 0.22 to >3 and their predicted non-conformance rates were close to those observed (23 to <0.001%). Required sample size ranged from 0.01 to 10%. Chosen techniques identified significant deviation from 'as validated' performance within an appropriate time-scale. Thus the methodology was straightforward to apply and prompted the choice of a clinically and operationally appropriate sampling regimen and analysis for each blood component parameter. This evidence-based, targeted use of SPC for blood component monitoring provides an essential focus on processes with a low capability in achieving their specifications.

Water and sediment as sources of phosphate in aquatic ecosystems: The Detroit River and its role in the Laurentian Great Lakes.

Eutrophication of freshwater ecosystems and harmful algal blooms (HABs) are an ongoing concern affecting water quality in the Great Lakes watershed of North America. Despite binational management efforts, Lake Erie has been at the center of dissolved reactive phosphate driven eutrophication research due to its repeated cycles of algae blooms. We investigated the Detroit River, the largest source of water entering Lake Erie, with the objectives to (1) characterize Detroit River phosphate levels within water and sediment, and (2) use multiple chemical and isotopic tracers to identify nutrient sources in the Detroit River. Riverine water and sediment samples were collected at 23 locations across 8 transects of the Detroit River. The bulk δ15N values from sediments were enriched compared the δ15N values of nitrate from water samples, consistent with biogeochemical cycling in the sediment. Principle component analysis of multiple chemical tracers from water samples found spatial variation consistent with multiple sources including synthetic and manure-derived fertilizers and wastewater effluent. The concentrations of phosphate dissolved in water were within regulatory guidelines; however, sediments had elevated concentrations of both water- and acid-extractable phosphate. Sediment-sequestered legacy phosphorus historically deposited in the Detroit River may be transported into Lake Erie and, if mobilized into the water column, be an unrecognized internal-load that contributes to algal bloom events. Globally, freshwater ecosystems are impacted by numerous non-point source phosphorus inputs contributing to eutrophication and the use of multiple tracer approaches will increase our ability to effectively manage aquatic ecosystems.

Geochemical and sulfate isotopic evolution of flowback and produced waters reveals water-rock interactions following hydraulic fracturing of a tight hydrocarbon reservoir.

Although multistage hydraulic fracturing is routinely performed for the extraction of hydrocarbon resources from low permeability reservoirs, the downhole geochemical processes linked to the interaction of fracturing fluids with formation brine and reservoir mineralogy remain poorly understood. We present a geochemical dataset of flowback and produced water samples from a hydraulically fractured reservoir in the Montney Formation, Canada, analyzed for major and trace elements and stable isotopes. The dataset consists in 25 samples of flowback and produced waters from a single well, as well as produced water samples from 16 other different producing wells collected in the same field. Additionally, persulfate breaker samples as well as anhydrite and pyrite from cores were also analyzed. The objectives of this study were to understand the geochemical interactions between formation and fracturing fluids and their consequences in the context of tight gas exploitation. The analysis of this dataset allowed for a comprehensive understanding of the coupled downhole geochemical processes, linked in particular to the action of the oxidative breaker. Flowback fluid chemistries were determined to be the result of mixing of formation brine with the hydraulic fracturing fluids as well as coupled geochemical reactions with the reservoir rock such as dissolution of anhydrite and dolomite; pyrite and organic matter oxidation; and calcite, barite, celestite, iron oxides and possibly calcium sulfate scaling. In particular, excess sulfate in the collected samples was found to be mainly derived from anhydrite dissolution, and not from persulfate breaker or pyrite oxidation. The release of heavy metals from the oxidation activity of the breaker was detectable but concentrations of heavy metals in produced fluids remained below the World Health Organization guidelines for drinking water and are therefore of no concern. This is due in part to the co-precipitation of heavy metals with iron oxides and possibly sulfate minerals.

An evaluation of proposed changes to International Standards for blood bags and transfusion sets to improve their compatibility.

Difficulties arising from the poor compatibility of some blood bag and transfusion set combinations remain a significant, ongoing patient safety issue. Proposed changes to international standards based on previously published findings provide a potential resolution when adopted by manufacturers. The aims and objectives of this study were to demonstrate that changes to ISO 3826-1 and 1135-4, especially surface treatment of the transfusion set spike (siliconisation) to reduce insertion force and accidental spiking will not result in: 'Pre-piercing' of the port membrane; difficulty in inserting the spike; leakage from the spike/port connection or unintentional removal of the spike during transfusion. The performance of connections (ports from five and siliconized spikes from two manufacturers) was assessed by a range of physical tests including: pressure tests for leakage at 50 kPa (1.5 bar); static stress (pull) tests at 15 and 20 N. Spike insertion force tests were repeated to challenge original findings. Of the 280 connections tested, there was one dubious pressure tests fail (<10 microL), no pull test failures at 15 N and one at 20 N. Spike insertion forces were acceptable and consistently low with ports from all manufacturers. Findings confirm the benefits of siliconized spikes in improving compatibility between transfusion sets and blood bags. This study does not indicate that the evaluated spikes would be subject to unintentional removal or leakage when used in accordance with manufacturer's instructions. Pressure and pull tests on spike/port connections are a valuable addition to ISO 3826-1 and 1135-4 for manufacturing design validation and quality control purposes.

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma.

In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (Delta13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n=794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if Delta13, p53 deletion or t(4;14) was present, but only Delta13 remained significant on multivariate analysis. Patients with Delta13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with Delta13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable Delta13 disappeared; their outcome matched that of patients with no detectable Delta13 (P=0.115). Addition of ploidy status to iFISH-Delta13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH Delta13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with Delta13. We conclude that Delta13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of Delta13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

Occurrence and origin of methane in groundwater in Alberta (Canada): Gas geochemical and isotopic approaches.

To assess potential future impacts on shallow aquifers by leakage of natural gas from unconventional energy resource development it is essential to establish a reliable baseline. Occurrence of methane in shallow groundwater in Alberta between 2006 and 2014 was assessed and was ubiquitous in 186 sampled monitoring wells. Free and dissolved gas sampling and measurement approaches yielded comparable results with low methane concentrations in shallow groundwater, but in 28 samples from 21 wells methane exceeded 10mg/L in dissolved gas and 300,000 ppmv in free gas. Methane concentrations in free and dissolved gas samples were found to increase with well depth and were especially elevated in groundwater obtained from aquifers containing coal seams and shale units. Carbon isotope ratios of methane averaged -69.7 ± 11.1‰ (n=63) in free gas and -65.6 ± 8.9‰ (n=26) in dissolved gas. δ(13)C values were not found to vary with well depth or lithology indicating that methane in Alberta groundwater was derived from a similar source. The low δ(13)C values in concert with average δ(2)HCH4 values of -289 ± 44‰ (n=45) suggest that most methane was of biogenic origin predominantly generated via CO2 reduction. This interpretation is confirmed by dryness parameters typically >500 due to only small amounts of ethane and a lack of propane in most samples. Comparison with mud gas profile carbon isotope data revealed that methane in the investigated shallow groundwater in Alberta is isotopically similar to hydrocarbon gases found in 100-250 meter depths in the WCSB and is currently not sourced from thermogenic hydrocarbon occurrences in deeper portions of the basin. The chemical and isotopic data for methane gas samples obtained from Alberta groundwater provide an excellent baseline against which potential future impact of deeper stray gases on shallow aquifers can be assessed.

Surface and bulk transitions in three-dimensional O(n) models.

Using Monte Carlo methods and finite-size scaling, we investigate surface criticality in the O(n) models on the simple-cubic lattice with n=1 , 2, and 3, i.e., the Ising, XY , and Heisenberg models. For the critical couplings we find Kc (n=2) =0.454 1659 (10) and Kc (n=3) =0.693 003 (2). We simulate the three models with open surfaces and determine the surface magnetic exponents at the ordinary transition to be y (o)(h1) =0.7374 (15) , 0.781 (2), and 0.813 (2) for n=1 , 2, and 3, respectively. Then we vary the surface coupling K1 and locate the so-called special transition at kappa(c) (n=1) =0.502 14 (8) and kappa(c) (n=2) =0.6222 (3), where kappa= K1 /K-1 . The corresponding surface thermal and magnetic exponents are y (s)(t1) =0.715 (1) and y (s)(h1) =1.636 (1) for the Ising model, and y(s)(t1) =0.608 (4) and y(s)(h1) =1.675 (1) for the XY model. Finite-size corrections with an exponent close to -1/2 occur for both models. Also for the Heisenberg model we find substantial evidence for the existence of a special surface transition.

A rapid non-radioactive procedure for plaque hybridization using biotinylated probes prepared by random primed labeling.

A simple, non-radioactive method has been developed for the rapid screening of phage libraries. In the present study, nanogram amounts of a small restriction fragment (135 bp) were biotinylated via random primed labeling and used to probe cDNA libraries using a modified plaque hybridization protocol. The high backgrounds that are seen typically with avidin/biotin-based methods for plaque hybridization were eliminated by incubation of filters with one of several different proteases prior to hybridization. A comparison of several detection systems indicated that streptavidin conjugated to calf intestinal alkaline phosphatase (AP) was the most sensitive, yielding signals comparable to those obtained with 32P-labeled probes. The times required for phage growth and pre-hybridization were reduced substantially, permitting a convenient one-day screening protocol. Nitrocellulose filters gave the best signal to noise ratio, although "streaking" of plaque DNA was observed occasionally; this problem can be overcome by using nylon-based membranes, which allows exact visualization of the positive plaques. The method was highly reliable; 29 out of 33 putative clones retested positive and the authenticity of these was confirmed by DNA sequence analysis. The random primed biotinylation procedure has been utilized successfully with several different cDNA fragments and has proven useful for other hybridization-based methods (Northern and Southern blots), without the problems associated with the use of radiolabeled probes.

Effects of toxic substances on female reproduction.

Successful reproduction requires a complex series of interdependent physiological, cellular and molecular events. In the female many of these interdependent events are vulnerable to interruption by xenobiotic compounds. The physiological steps in the female reproductive cycle are reviewed. Selected xenobiotics which interrupt this cycle are presented and their mechanisms and site of adverse effects are discussed. Finally, a more detailed discussion of chemically induced ovarian failure in the human and an experimental animal model system is presented.

Care management of work injuries: results of a 1-year pilot outcome assurance program.

A 1-year pilot study was conducted, linking the efforts of a workers' compensation managed care organization with those of an occupational health clinic and emergency department of manage work-related injuries and associated work disability. Sustained (> 90 day), injury-specific return-to-work outcomes, modified by job title, were compared with loosely managed and well-managed benchmarks. The mean return-to-work outcome, measured as lost workdays (LWDs), was 5.11 +/- 21.0 LWDs for 418 workers. These results exceeded benchmarks for both loosely managed care, 14.0 +/- 17.2 LWDs, P < 0.001 (8.9 fewer LWDs/case), and optimally case-managed care, 6.99 +/- 7.64 LWDs, P = 0.044 (1.9 fewer LWDs/case). An estimate of the value of these saved LWDs to the employers-at $200 per workday was $740,400 for the loosely managed benchmarks and $157,000 for the well-managed benchmarks. The Outcome Assurance Program virtually eliminated typical delays in the diagnosis and medical management of these injured workers.