Physical activity is associated with lower insulin and C-peptide during glucose challenge in children and adolescents with family background of diabetes.

AIMS: Children and adolescents with a family history of diabetes are at increased risk of overweight, but little is known about the potentially beneficial effects of physical activity on these children. The objective of this study was to investigate the association between moderate to vigorous physical activity (MVPA) and metabolic and inflammatory risks in children and adolescents with a family background of Type 1 diabetes or gestational diabetes. METHODS: Valid MVPA measurements, made with accelerometers, were available from 234 participants (median age, 10.2 years) who had a first-degree relative with either Type 1 or gestational diabetes. Anthropometric and metabolic measurements were made and cytokines measured, and were correlated with MVPA measurements, with stepwise adjustment for confounding factors, in a cross-sectional analysis. RESULTS: MVPA was negatively associated with insulin and C-peptide during challenge with an oral glucose tolerance test. MVPA was also significantly positively associated with the insulin sensitivity index, whereas no consistently significant associations were found between MVPA and BMI, blood pressure or cytokine levels. DISCUSSION: Our findings indicate that physical activity may have beneficial effects on insulin and C-peptide metabolism in children and adolescents with a family background of diabetes, but show no evidence of a protective association with other health-related outcomes.

Risk Stratification in Women with Gestational Diabetes According to and Beyond Current WHO Criteria.

The pregnancy outcomes in women with gestational diabetes mellitus (GDM) and 'overt diabetes in pregnancy' were compared and the need for further subclassification was investigated with respect to postpartum outcome risk. Data from 944 women who had been uniformly diagnosed as having GDM in Munich, Germany, between 1998 and 2010, were re-classified into GDM and 'overt diabetes in pregnancy'. Pregnancy related outcomes in the offspring were derived from Bavarian birth registry data. Classification and regression trees were used to identify further GDM sub-phenotypes. In total, 88 women (9.3%) were re-classified as having 'overt diabetes in pregnancy'. Compared to women with GDM, women with 'overt diabetes in pregnancy' used insulin more frequently, and were at increased risk for large for gestational age infants [odds ratio 2.50 (95% confidence interval 1.02, 6.13)], preterm delivery [odds ratio 3.28 (1.02, 10.50)], and low APGAR-score at 5 min [odds ratio 12.70 (1.58, 102.2)]. In the 856 women with GDM, classification and regression tree analyses provided further risk stratification in that a combination of fasting glucose>5.3 mmol/l and 1-h glucose>11.1 mmol/l at GDM diagnosis predicted insulin requirement [OR 5.57 (3.75, 8.27) compared to the rest], and maternal body mass index (BMI)≥35 kg/m(2) predicted large for gestational age status. The new differentiation between GDM and 'overt diabetes in pregnancy' is a first step towards refining classification relevant to fetal and maternal postpartum risk. A combination of glucose levels and maternal BMI at diagnosis of GDM may provide further improvement.

Systematic review, network meta-analysis and exploratory cost-effectiveness model of randomized trials of minimally invasive techniques versus surgery for varicose veins.

BACKGROUND: A Health Technology Assessment was conducted to evaluate the relative clinical effectiveness and cost-effectiveness of minimally invasive techniques (foam sclerotherapy (FS), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA)) for managing varicose veins, in comparison with traditional surgery. METHODS: A systematic review of randomized clinical trials (RCTs) was undertaken to assess the effectiveness of minimally invasive techniques compared with other treatments, principally surgical stripping, in terms of recurrence of varicose veins, Venous Clinical Severity Score (VCSS), pain and quality of life. Network meta-analysis and exploratory cost-effectiveness modelling were performed. RESULTS: The literature search conducted in July 2011 identified 1453 unique citations: 31 RCTs (51 papers) satisfied the criteria for effectiveness review. Differences between treatments were negligible in terms of clinical outcomes, so the treatment with the lowest cost appears to be most cost-effective. Total FS costs were estimated to be lowest, and FS was marginally more effective than surgery. However, relative effectiveness was sensitive to the model time horizon. Threshold analysis indicated that EVLA and RFA might be considered cost-effective if their costs were similar to those for surgery. These findings are subject to various uncertainties, including the risk of bias present in the evidence base and variation in reported costs. CONCLUSION: This assessment of currently available evidence suggests there is little to choose between surgery and the minimally invasive techniques in terms of efficacy or safety, so the relative cost of the treatments becomes one of the deciding factors. High-quality RCT evidence is needed to verify and further inform these findings.

Resting and exercise haemodynamic characteristics of patients with advanced heart failure and preserved ejection fraction.

AIMS: This study aimed to describe haemodynamic features of patients with advanced heart failure with preserved ejection fraction (HFpEF) as defined by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). METHODS AND RESULTS: We used pooled data from two dedicated HFpEF studies with invasive exercise haemodynamic protocols, the REDUCE LAP-HF (Reduce Elevated Left Atrial Pressure in Patients with Heart Failure) trial and the REDUCE LAP-HF I trial, and categorized patients according to advanced heart failure (AdHF) criteria. The well-characterized HFpEF patients were considered advanced if they had persistent New York Heart Association classification of III-IV and heart failure (HF) hospitalization < 12 months and a 6 min walk test distance < 300 m. Twenty-four (22%) out of 108 patients met the AdHF criteria. On evaluation, clinical characteristics and resting haemodynamics were not different in the two groups. Patients with AdHF had lower work capacity compared with non-advanced patients (35 ± 16 vs. 45 ± 18 W, P = 0.021). Workload-corrected pulmonary capillary wedge pressure normalized to body weight (PCWL) was higher in AdHF patients compared with non-advanced (112 ± 55 vs. 86 ± 49 mmHg/W/kg, P = 0.04). Further, AdHF patients had a smaller increase in cardiac index during exercise (1.1 ± 0.7 vs. 1.6 ± 0.9 L/min/m2 , P = 0.028). CONCLUSIONS: A significantly higher PCWL and lower cardiac index reserve during exercise were observed in AdHF patients compared with non-advanced. These differences were not apparent at rest. Therapies targeting the haemodynamic compromise associated with advanced HFpEF are needed.

Human enterovirus infections in children at increased risk for type 1 diabetes: the Babydiet study.

AIMS/HYPOTHESIS: The aim of this study was to examine human enteroviruses (HEVs) and other intestinal viruses derived from children who participated in the Babydiet intervention study and to analyse the findings according to the appearance of islet autoantibodies, dietary intervention, maternal type 1 diabetes and clinical symptoms. METHODS: In the Babydiet study the influence of first gluten exposure (6 or 12 months) on the development of islet autoimmunity was investigated in 150 children with increased genetic and familial risk for type 1 diabetes. Blood and stool samples were collected at 3 monthly intervals until the age of 3 years and yearly thereafter. Infections and clinical symptoms were recorded daily for the first year. In the present study, 339 stool samples collected from 104 children during the first year of life were analysed for HEVs and a certain proportion of the samples were analysed for other intestinal viruses. RESULTS: HEV was detected in 32 (9.4%) samples from 24 (23.1%) children. Altogether 13 serotypes were identified, with HEV-A species being the most common. Children with gastrointestinal symptoms had norovirus (3/11) and sapovirus (1/11) infections in addition to HEV (1/11). Of the 104 children, 22 developed islet autoantibodies. HEV infections were detected in 18% (4/22) and 24% (20/82) of islet-autoantibody-positive and -negative children, respectively (p = 0.5). The prevalence of HEV was similar in the gluten-exposed groups and in children from mothers with type 1 diabetes or from affected fathers and/or siblings (p = 1.0 and 0.6, respectively). CONCLUSIONS/INTERPRETATION: No correlation was found between the presence of HEV in the first year of life and the development of islet autoantibodies. There was no association between HEV infections and dietary intervention, maternal diabetes or clinical symptoms.

Early infant diet in children at high risk for type 1 diabetes.

Infant diet affects health and development. The aim of our study was to investigate WHO infant feeding compliance in children who have a first degree family history of type 1 diabetes (T1D). One hundred and fifty children who were first degree relatives of patients with T1D were intensively followed from birth in the BABYDIET intervention study. Infant feeding, infections, and medication were recorded daily by participating families. Weight and length of children were obtained from paediatric records. Only 5% of the families followed the WHO recommendations for infant feeding that include full breastfeeding for at least 6 months (18.8% of children) and introduction of complementary foods under continued breastfeeding thereafter (22.2% of children). Maternal age in the first quartile (<29 years; p<0.0001), and maternal smoking (p<0.0001) were associated with an earlier introduction of solid food and reduced breastfeeding. Full breastfeeding > or =6 months was associated with reduced frequency of gastrointestinal infections (12 vs. 38%, p=0.02) and antibiotic treatment (24 vs. 48%, p=0.04). Our findings indicate that WHO infant feeding recommendations were poorly followed by families with a family history of T1D. Action to improve levels of infant feeding behaviour is essential, especially among young mothers with T1D.

Identification of historical specimens and wildlife seizures originating from highly degraded sources of kangaroos and other macropods.

Forensic investigations are an important area in the regulation of food mis-description, wildlife seizures and the international trade in wildlife and its products. An early, but important stage in dealing with many biological materials that are submitted for forensic scrutiny is species identification. We describe a method and new primers to amplify three small DNA fragments of the cytochrome b region of the mitochondrial DNA that are suitable for marsupial species identification from degraded sources, such as wildlife seizures. They were designed as consensus sequences from a comparison of 21 marsupial species. The primers also contained sequences intended specifically not to amplify human DNA, thereby reducing the likelihood of amplifying contaminants. Examples of the utility of these primers are given using a range of conditions that may be applied using such an approach, including (1) field-collected sub-fossil bones, (2) an example of museum mis-identification from a specimen collected in 1930 and (3) a skull collected from Bernier Island, in the harsh mid-west of Western Australia.

Gait deviations in transverse plane after SCFE in dependence on the femoral offset.

Residual deformity of the femoral head after slipped capital femoral epiphysis (SCFE) may be accompanied by a loss of femoral offset and lead to femoro-acetabular impingement (FAI), especially during hip flexion. It is hypothesized that during phases of the gait cycle, when the hip is flexed, the offset-loss is compensated by an increased external rotation. The gait pattern of 36 patients suffering from SCFE, who were treated by pinning-in-situ, were compared to a control group of 40 healthy adults by an instrumented 3D-gait analysis. Total patient group was subdivided into 3 subgroups in dependence on the offset (offset groups (OG)) quantified by the angle α according to Nötzli: OG1: α-angle <55°, OG2: α-angle between 55 and 75°, OG3: α-angle >75°. Comparisons were made at 3 instants: initial foot contact (0% gait cycle (GC)), 40-60% GC and 90-100% GC. Patients showed an increased external hip rotation during all 3 periods of the GC with a tendency of increasing external rotation in association with offset-loss. Only during hip extension (40-60% GC) there was a weak correlation between angle α and hip rotation (r=-0.375, p=0.024). In conclusion, the offset-loss does not lead to a functional relevant impingement during walking which needs compensation strategies like increasing external rotation during periods of hip flexion.

High-dose carboplatin with diethyldithiocarbamate chemoprotection in treatment of women with relapsed ovarian cancer.

Diethyldithiocarbamate (DDTC) has been found to protect the bone marrow, kidneys, and gastrointestinal tract from the toxic effects of cisplatin and carboplatin (CBDCA) in animal models. In an attempt to minimize the toxic effects of high-dose CBDCA (800 mg/m2), a pilot study was undertaken in which women with relapsed or refractory epithelial ovarian cancer were treated with high-dose CBDCA, which was followed 3 hours later with DDTC (4 g/m2). There were four partial responses and no complete response in 21 patients who could be evaluated (overall response rate, 19%). Significant toxic effects, including three treatment-related deaths, were associated with the regimen. This study suggests that while high-dose CBDCA plus DDTC may be active in relapsed or refractory ovarian cancer, it is associated with clinically significant hematologic and autonomic toxic effects.

Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study.

PURPOSE: This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy. PATIENTS AND METHODS: Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol. RESULTS: Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (< 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each. CONCLUSION: Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.

Automatic selection of non-coplanar beam directions for three-dimensional conformal radiotherapy.

An algorithm is described, based on ray-tracing and the beam's-eye-view, that exhaustively searches all permitted beam directions. The evaluation of the search is based on a general cost function that can be adapted to the clinical objectives by means of parameters and weighting factors. The approach takes into account the constraints of the linear accelerator by discarding beam directions that are not permitted. A sensitivity analysis was carried out to determine appropriate parameters for different sized organs, and a prostate case was used to benchmark the approach. The algorithm was also applied to two clinical cases (brain and sinus) to test the benefits of the approach compared with manual angle selection. The time to perform a beam direction search was approximately 2 min for the coplanar and 12 min for the non-coplanar beam space. The angles obtained for the prostate case compared well with reports in the literature. For the brain case, the mean dose to the right and left optic nerves was reduced by 12% and 50%, respectively, whilst the target dose uniformity was improved. For the sinus case, the mean doses to the right and left parotid glands were reduced by 54% and 46%, respectively, to the right and left optic nerves by 37% and 62%, respectively, and to the optic chiasm by 39%, whilst the target dose uniformity was also improved. For the clinical cases the plans based on optimized beam directions were simpler and resulted in better sparing of critical structures compared with plans based on manual angle selection. The approach provides a practical alternative to elaborate and time consuming beam angle optimization schemes and is suitable for routine clinical usage.

Xylazine-induced hyperglycemia in cattle: a possible involvement of alpha 2-adrenergic receptors regulating insulin release.

The mechanism by which xylazine raises plasma glucose but lowers insulin concentrations was examined in Holstein cows. Intravenous injection of xylazine (15-150 micrograms/kg) induced a dose-dependent hyperglycemia and hypoinsulinemia for 3-4 h. An alpha 2-adrenergic blocking agent, yohimbine, and an alpha 1- and alpha 2-adrenergic blocking agent, phentolamine, at 500 micrograms/kg each reduced or abolished xylazine-induced hyperglycemia and hypoinsulinemia. The alpha 1-adrenergic blocking agents, prazosin and phenoxybenzamine, at 500 micrograms/kg each did not exert such antagonism. Prazosin at the dose studied even prolonged xylazine-induced hypoinsulinemia. The alpha-adrenergic blocking agents alone at 500 micrograms/kg each did not change either plasma glucose or insulin concentrations. The present study suggests that xylazine-induced hyperglycemia and hypoinsulinemia are mediated by alpha 2-adrenergic receptors, possibly in beta-cells of pancreatic islets which inhibit the release of insulin. The present study further suggests the use of xylazine as a pharmacological tool in the study of adrenergic influence on in vivo insulin release.

Reconstruction of a historical genealogy by means of STR analysis and Y-haplotyping of ancient DNA.

Archaeological excavations in St Margaretha's church at Reichersdorf, Germany, in 1993 led to the discovery of eight skeletons, so far assumed to be of the Earls of Königsfeld, who used the church as a family sepulchre over a period of seven generations from 1546 to 1749. DNA-based sex testing and analysis of autosomal short tandem repeat systems (STR) was carried out to confirm the assumption of kinship. Since five of the individuals were determined as males, analysis of Y-specific STRs seemed feasible. A comparison of Y-haplotypes revealed that one individual could not be linked to the Königsfeld patrilineage, an observation supported by autosomal STR evidence. Two individuals typed as females posed an identification problem, since supposedly only male members of the family were buried in St Margaretha's. Nevertheless, these individuals could tentatively be identified as members of the House of Königsfeld through genetic fingerprinting.

Cloning of an Arabidopsis histidine transporting protein related to nitrate and peptide transporters.

In plants, many of the proteins involved in transport of nitrogenous compounds have not been identified so far. The use of heterologous complementation in yeast mutants has enabled the isolation of a gene family encoding amino acid permease (AAP). A highly sensitive selection procedure was used to identify other proteins capable of transporting amino acids. In addition to members of the AAP gene family, an integral membrane protein (NTR1) that shows significant similarities to the low affinity nitrate transporter from Arabidpsis and to peptide transporters from yeast and rabbit was identified. NTR1 seems to be involved in the supply of reproductive organs with nitrogen as it is expressed at low levels in leaves and highly in developing pods.

Consistency of three-dimensional planning target volumes across physicians and institutions.

PURPOSE: Three-dimensional treatment planning depends upon exact and consistent delineation of target volumes. This study tested whether different physicians from different institutions vary significantly in their creation of planning target volumes (PTVs). METHODS AND MATERIALS: Eight physicians from three different institutions created partial planning target volumes for nine clinical test cases. Their target volumes were evaluated qualitatively and quantitatively. Quantitative results were tested for significant differences. RESULTS: Qualitative analysis showed the physicians to vary in (a) the margin placed around the clinical target volume, (b) the margin used near critical structures, and (c) handling of concavities in the clinical target volume. Quantitative analysis showed these variations to result in statistically significant differences in the measured volume of the physicians' planning target volumes. CONCLUSIONS: Individual physicians and institutions differ significantly in their creation of planning target volumes, suggesting individual and institutional differences in the working definition for the PTV. Implications of this fact are discussed, along with areas where standardization can be improved.

Three dimensional planning target volumes: a model and a software tool.

PURPOSE: Three dimensional (3D) target volumes are an essential component of conformal therapy because the goal is to shape the treatment volume to the target volume. The planning target volume (PTV) is defined by ICRU 50 as the clinical target volume (CTV) plus a margin to ensure that the CTV receives the prescribed dose. The margin must include all interfractional and intrafractional treatment variations. This paper describes a software tool that automatically generates 3D PTVs from CTVs for lung cancers and immobile head and neck cancers. METHODS AND MATERIALS: Values for the interfractional and intrafractional treatment variations were determined by a literature review and by targeted interviews with physicians. The software tool is written in Common LISP and conforms to the specifications for shareable software of the Radiotherapy Treatment Planning Tools Collaborative Working Group. RESULTS: The tool is a rule-based expert system in which the inputs are the CTV contours, critical structure contours, and qualitative information about the specific patient. The output is PTV contours, which are a cylindrical expansion of the CTV. A model for creating PTVs from CTVs is embedded in the tool. The interfractional variation of setup uncertainty and the intrafractional variations of movement of the CTV (e.g., respiration) and patient motion are included in the model. Measured data for the component variations is consistent with modeling the components as independent samples from 3D Gaussian distributions. The components are combined using multivariate normal statistics to yield the cylindrical expansion factors. Rules are used to represent the values of the components for certain patient conditions (e.g., setup uncertainty for a head and neck patient immobilized in a mask). The tool uses a rule interpreter to combine qualitative information about a specific patient with rules representing the value of the components and to enter the appropriate component values for that patient into the cylindrical expansion formula. CONCLUSION: The portable software tool allows the rapid, consistent, and automatic generation of 3D PTVs from CTVs.

Prism: a new approach to radiotherapy planning software.

PURPOSE: We describe the capabilities and performance of Prism, an innovative new radiotherapy planning system with unusual features and design. The design and implementation strategies are intended to assure high quality and clinical acceptability. The features include Artificial Intelligence tools and special support for multileaf collimator (MLC) systems. The design provides unusual flexibility of operation and ease of expansion. METHODS AND MATERIALS: We have implemented Prism, a three-dimensional (3D) radiotherapy treatment-planning system on standard commercial workstations with the widely available X window system. The design and implementation use ideas taken from recent software engineering research, for example, the use of behavioral entity-relationship modeling and the "Mediator Method" instead of ad-hoc programming. The Prism system includes the usual features of a 3D planning system, including Beam's Eye View and the ability to simulate any treatment geometry possible with any standard radiotherapy accelerator. It includes a rule-based expert system for automated generation of the planning target volume as defined in ICRU Report 50. In addition, it provides special support for planning treatments with a multileaf collimator (MLC). We also implemented a Radiotherapy Treatment Planning Tools Foundation for Prism, so that we are able to use software tools form other institutions without any source code modification. RESULTS: The Prism system has been in clinical operation at the University of Washington since July 1994 and has been installed at several other clinics. The system is run simultaneously by several users, each with their own workstation operating from a common networked database and software. In addition to the dosimetrists, the system is used by radiation oncologists to define tumor and target volumes and by radiation therapists to select treatment setups to load into a computer controlled accelerator. CONCLUSIONS: Experience with the installation and operation has shown the design to be effective as both a clinical and research tool. Integration of software tools has eased the development and significantly enhanced the clinical usability of the system. The design has been shown to be a sound basis for further innovation in radiation treatment planning software and for research in the treatment planning process.

Impact of a multileaf collimator on treatment morbidity in localized carcinoma of the prostate.

PURPOSE: To evaluate the effectiveness of variable multileaf collimation, three-dimensional treatment planning, and computer-controlled conformal radiation therapy of prostate cancer. METHODS AND MATERIALS: Two hundred and forty-five patients with locally advanced prostate cancer have completed treatment over a 9-year time span using a multileaf collimator and conformal treatment techniques on the University of Washington cyclotron. All patients had three-dimensional treatment planning with computed tomography scans in the treatment position, and had treatment fields individually shaped to the target volume with a continuously variable multileaf collimator. Treatment was delivered under computer control with network transfer of the multileaf collimator settings from the treatment planning computer to the cyclotron control system. RESULTS: The multileaf collimator combined with three-dimensional treatment planning results in elegant dose distributions. These neuron dose distributions resulted in a reduced local/regional tumor failure rate with no increase in complications when compared to control treatment with photons in a randomized trial. Neutron treatment delivered at other institutions without conformal beam shaping resulted in the same improvement in local-regional tumor control rates, but was associated with a significantly higher normal tissue complication rate than seen with conformal neutron beam delivery techniques (grade 3 and 4 cumulative late normal tissue toxicity rates of 39% vs. 10%, p = 0.0007). CONCLUSIONS: Conformal treatment of prostate cancer using a multileaf collimated neutron beam results in increased local/regional tumor control rates with low normal tissue toxicities. This experience is directly applicable to the conformal treatment of prostate cancer with photons.

Automated planning target volume generation: an evaluation pitting a computer-based tool against human experts.

PURPOSE: Software tools are seeing increased use in three-dimensional treatment planning. However, the development of these tools frequently omits careful evaluation before placing them in clinical use. This study demonstrates the application of a rigorous evaluation methodology using blinded peer review to an automated software tool that produces ICRU-50 planning target volumes (PTVs). METHODS AND MATERIALS: Seven physicians from three different institutions involved in three-dimensional treatment planning participated in the evaluation. Four physicians drew partial PTVs on nine test cases, consisting of four nasopharynx and five lung primaries. Using the same information provided to the human experts, the computer tool generated PTVs for comparison. The remaining three physicians, designated evaluators, individually reviewed the PTVs for acceptability. To exclude bias, the evaluators were blinded to the source (human or computer) of the PTVs they reviewed. Their scorings of the PTVs were statistically examined to determine if the computer tool performed as well as the human experts. RESULTS: The computer tool was as successful as the human experts in generating PTVs. Failures were primarily attributable to insufficient margins around the clinical target volume and to encroachment upon critical structures. In a qualitative analysis, the human and computer experts displayed similar types and distributions of errors. CONCLUSIONS: Rigorous evaluation of computer-based radiotherapy tools requires comparison to current practice and can reveal areas for improvement before the tool enters clinical practice.

Minimization and management of wastes from biomedical research.

Several committees were established by the National Association of Physicians for the Environment to investigate and report on various topics at the National Leadership Conference on Biomedical Research and the Environment held at the 1--2 November 1999 at the National Institutes of Health in Bethesda, Maryland. This is the report of the Committee on Minimization and Management of Wastes from Biomedical Research. Biomedical research facilities contribute a small fraction of the total amount of wastes generated in the United States, and the rate of generation appears to be decreasing. Significant reductions in generation of hazardous, radioactive, and mixed wastes have recently been reported, even at facilities with rapidly expanding research programs. Changes in the focus of research, improvements in laboratory techniques, and greater emphasis on waste minimization (volume and toxicity reduction) explain the declining trend in generation. The potential for uncontrolled releases of wastes from biomedical research facilities and adverse impacts on the general environment from these wastes appears to be low. Wastes are subject to numerous regulatory requirements and are contained and managed in a manner protective of the environment. Most biohazardous agents, chemicals, and radionuclides that find significant use in research are not likely to be persistent, bioaccumulative, or toxic if they are released. Today, the primary motivations for the ongoing efforts by facilities to improve minimization and management of wastes are regulatory compliance and avoidance of the high disposal costs and liabilities associated with generation of regulated wastes. The committee concluded that there was no evidence suggesting that the anticipated increases in biomedical research will significantly increase generation of hazardous wastes or have adverse impacts on the general environment. This conclusion assumes the positive, countervailing trends of enhanced pollution prevention efforts by facilities and reductions in waste generation resulting from improvements in research methods will continue.