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Background Approximately half of high‐grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination repair (HR) pathway defects, resulting in a distinct clinical phenotype comprising hypersensitivity to platinum, superior clinical outcome, and greater sensitivity to poly(adenosine diphosphate‐ribose) polymerase (PARP) inhibitors. EMSY, which is known to be amplified in breast and ovarian cancers, encodes a protein reported to bind and inactivate BRCA2. Thus, EMSY overexpression may mimic BRCA2 mutation, resulting in HR deficiency. However, to our knowledge, the phenotypic consequences of EMSY overexpression in HGSOC patients has not been explored. Methods Here we investigate the impact of EMSY expression on clinical outcome and sensitivity to platinum‐based chemotherapy using available data from transcriptomically characterized HGSOC cohorts. Results High EMSY expression was associated with better clinical outcome in a cohort of 265 patients with HGSOC from Edinburgh (overall survival multivariable hazard ratio, 0.58 [95% CI, 0.38‐0.88; P = .011] and progression‐free survival multivariable hazard ratio, 0.62 [95% CI, 0.40‐0.96; P = .030]). Superior outcome also was demonstrated in the Medical Research Council ICON7 clinical trial and multiple publicly available data sets. Patients within the Edinburgh cohort who had high EMSY expression were found to demonstrate greater rates of complete response to multiple platinum‐containing chemotherapy regimens (radiological complete response rate of 44.4% vs 12.5% at second exposure; P = .035) and corresponding prolonged time to disease progression (median, 151.5 days vs 60.5 days after third platinum exposure; P = .004). Conclusions Patients with HGSOCs demonstrating high EMSY expression appear to experience prolonged survival and greater platinum sensitivity, reminiscent of BRCA‐mutant cases. These data are consistent with the notion that EMSY overexpression may render HGSOCs HR deficient., Patients with high‐grade serous ovarian carcinomas demonstrating high expression levels of EMSY appear to experience prolonged survival and hypersensitivity to multiple lines of platinum‐based chemotherapy. These data support the notion that overexpression of the gene product of EMSY, which is reported to bind and inactivate BRCA2, may mimic the phenotype conferred by BRCA mutation.

The open field is a classic test used to assess exploratory behavior, anxiety and locomotor activity in rodents. Here, we mapped quantitative trait loci (QTLs) underlying behaviors displayed in an open field, using a panel of 53 BXD recombinant inbred mouse strains with deep replication (10 per strain and sex). The use of these strains permits the integration and comparison of data obtained in different laboratories, and also offers the possibility to study trait covariance by exploiting powerful bioinformatics tools and resources. We quantified behavioral traits during 20-min test sessions including (1) percent time spent and distance traveled near the wall (thigmotaxis), (2) leaning against the wall, (3) rearing, (4) jumping, (5) grooming duration, (6) grooming frequency, (7) locomotion and (8) defecation. All traits exhibit moderate heritability making them amenable to genetic analysis. We identified a significant QTL on chromosome M.m. 4 at approximately 104 Mb that modulates grooming duration in both males and females (likelihood ratio statistic values of approximately 18, explaining 25% and 14% of the variance, respectively) and a suggestive QTL modulating locomotion that maps to the same locus. Bioinformatic analysis indicates Disabled 1 (Dab1, a key protein in the reelin signaling pathway) as a particularly strong candidate gene modulating these behaviors. We also found 2 highly suggestive QTLs for a sex by strain interaction for grooming duration on chromosomes 13 and 17. In addition, we identified a pairwise epistatic interaction between loci on chromosomes 12 at 36-37 Mb and 14 at 34-36 Mb that influences rearing frequency in males.

STUDY QUESTION What is the impact of administration of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) on the endometrium of women with fibroids? SUMMARY ANSWER UPA administration altered expression of sex-steroid receptors and progesterone-regulated genes and was associated with low levels of glandular and stromal cell proliferation. WHAT IS KNOWN ALREADY Administration of all SPRM class members results in PAEC (progesterone receptor modulator associated endometrial changes). Data on the impact of the SPRM UPA administration on endometrial sex-steroid receptor expression, progesterone (P)-regulated genes and cell proliferation are currently lacking. STUDY DESIGN SIZE, DURATION Observational study with histological and molecular analyses to delineate impact of treatment with UPA on endometrium. Endometrial samples (n = 9) were collected at hysterectomy from women aged 39 to 49 with uterine fibroids treated with UPA (oral 5 mg daily) for 9–12 weeks. Control proliferative (n = 9) and secretory (n = 9) endometrium from women aged 38–52 with fibroids were derived from institutional tissue archives. PARTICIPANTS/MATERIALS, SETTING, METHODS Study setting was a University Research Institute. Endometrial biopsies were collected with institutional ethical approval and written informed consent. Concentrations of mRNAs encoded by steroid receptors, P-regulated genes and factors in decidualised endometrium were quantified with qRT-PCR. Immunohistochemistry was employed for localization of progesterone (PR, PRB), androgen (AR), estrogen (ERα) receptors and expression of FOXO1, HAND2, HOXA10, PTEN homologue. Endometrial glandular and stromal cell proliferation was objectively quantified using Ki67. MAIN RESULTS AND THE ROLE OF CHANCE UPA induced morphological changes in endometrial tissue consistent with PAEC. A striking change in expression patterns of PR and AR was detected compared with either proliferative or secretory phase samples. There were significant changes in pattern of expression of mRNAs encoded by IGFBP-1, FOXO1, IL-15, HAND2, IHH and HOXA10 compared with secretory phase samples consistent with low agonist activity in endometrium. Expression of mRNA encoded by FOXM1, a transcription factor implicated in cell cycle progression, was low in UPA-treated samples. Cell proliferation (Ki67 positive nuclei) was lower in samples from women treated with UPA compared with those in the proliferative phase. LARGE SCALE DATA N/A. LIMITATIONS REASONS FOR CAUTION A small number of well-characterized patients were studied in-depth. The impacts on morphology, molecular and cellular changes with SPRM, UPA administration on symptom control remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS P plays a pivotal role in endometrial function. P-action is mediated through interaction with the PR. These data provide support for onward development of the SPRM class of compounds as effective long-term medical therapy for heavy menstrual bleeding. STUDY FUNDING/COMPETING INTEREST(S) H.O.D.C. received has clinical research support for laboratory consumables and staff from Bayer Pharma Ag and provides consultancy advice (no personal remuneration) for Bayer Pharma Ag, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc.; A.R.W.W. has received consultancy payments from Bayer, Gedeon Richter, Preglem SA, HRA Pharma; L.H.R.W., A.A.M., R.M., G.S. and P.T.K.S. have no conflicts of interest. Study funded in part from each of: Medical Research Council (G1002033; G1100356/1; MR/N022556/1); National Health Institute for Health Research (12/206/520) and TENOVUS Scotland.

BACKGROUND Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and ‘atypical’ forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging. OBJECTIVE AND RATIONALE EC is the most common gynaecological malignancy in developed countries. The incidence of EC is rising, with alarming increases described in the 40–44-year-old age group. This review appraises the current EH classification systems used to stratify women at risk of malignant progression to EC. In addition, we summarize the evidence base regarding the use of immunohistochemical biomarkers for EH and discuss an emerging role for genomic analysis. SEARCH METHODS PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2000 to January 2016. The following search terms were used: ‘endometrial hyperplasia’, ‘endometrial intraepithelial neoplasia’, ‘atypical hyperplasia’, ‘complex atypical hyperplasia’, ‘biomarker’, ‘immunohistochemistry’, ‘progression’, ‘genomic’, ‘classification’ and ‘stratification’. OUTCOMES Recent changes to EH classification reflect our current understanding of the genesis of endometrioid ECs. The concept of endometrial intraepithelial neoplasia (EIN) as a mutationally activated, monoclonal pre-malignancy represents a fundamental shift from the previously held notion that unopposed oestrogenic stimulation causes ever-increasing hyperplastic proliferation, with accumulating cytological atypia that imperceptibly leads to the development of endometrioid EC. Our review highlights several key biomarker candidates that have been described as both diagnostic tools for EH and markers of progression to EC. We propose that, moving forwards, a ‘panel’ approach of combinations of the immunohistochemical biomarkers described in this review may be more informative since no single candidate can currently fill the entire role. WIDER IMPLICATIONS EC has historically been considered a predominantly postmenopausal disease. Owing in part to the current unprecedented rates of obesity, we are starting to see signs of a shift towards a rising incidence of EC amongst pre- and peri-menopausal woman. This creates unique challenges both diagnostically and therapeutically. Furthering our understanding of the premalignant stages of EC development will allow us to pursue earlier diagnosis and facilitate appropriate stratification of women at risk of developing EC, permitting timely and appropriate therapeutic interventions.

The “age” of a sample of uranium is an important aspect of a nuclear forensic investigation and of the attribution of the material to a source. The 230Th- 234U chronometer can be used to determine the production date of even very recently-produced material ( 234U half life = 245250 ± 490 years; 230Th half life = 75690 ± 230 years [1]), provided that the 230Th/234U at the time of formation is known, and that there has been no Th-U fractionation in the sample since production. For most samples of uranium, ages determined with this chronometer are “model ages”, because they are based on the assumptions of a) some initial amount of 230Th in the sample, and b) closed-system behavior of the sample since production. The uranium standard reference materials originally prepared and distributed by the former US National Bureau of Standards and now distributed by New Brunswick Laboratory as certified reference materials (NBS SRM = NBL CRM) are good candidates for materials where these assumptions may be tested. The U isotopic standards have known purification and production dates and closed-system behavior in the solid form (U3O8) may be reliably assumed. In addition, these materials are widely available and can serve as informal round-robin inter-laboratory comparison samples. We determined 230Th-234U model ages for seven of these isotopic standards by isotope dilution mass spectrometry using a multi-collector ICP-MS. The standards dated for this study are U005-A, U010, U030-A, U100, U850, U900 and U970. Model ages obtained range from ∼ 30 to ∼ 52 years ago (reference date: 5-May-2009). The model age of U100 is the same as the purification date, within uncertainty. The other six standards analyzed all give model ages older than the purification dates of record. The magnitude of the discrepancy between model age and purification date does not correlate with the model age or the amount of 232Th in the samples. This indicates that excess 230Th in these six standards results from incomplete purification during production.

This report describes an analysis of 244Pu from VNIIEF (FP-33) sent to the Lawrence Livermore National Laboratory as test samples.

Study objective: Error in determination of disease outcome occurs in epidemiology, but such error is not usually corrected for in statistical analysis. A method of correction of risk estimates for misclassification of a binary disease outcome is developed here. Methods: The method is a simple, closed form correction to the logistic regression estimate. A closed form variance estimate is also developed. Setting: The method is illustrated in two studies, a cross sectional survey of cervicitis in Iran in 1996–97, as determined by inflammation on cervical smear specimens, and a case-cohort study of benign proliferative epithelial disease of the breast, in Canada 1980–88. Main results: The method provides corrected odds ratio estimates and corrects the spurious precision conferred by misclassification. Conclusions: The method is easy to apply and potentially useful, although potential failures of the assumptions involved should be borne in mind. It is necessary to give careful consideration to the plausibility or otherwise of the assumptions in the context of the individual study. Correction for misclassification of disease outcome may become more common with the development of readily applicable methods.

The collection of real-time air quality measurements while in motion (i.e., mobile monitoring) is currently conducted worldwide to evaluate in situ emissions, local air quality trends, and air pollutant exposure. This measurement strategy pushes the limits of traditional data analysis with complex second-by-second multipollutant data varying as a function of time and location. Data reduction and filtering techniques are often applied to deduce trends, such as pollutant spatial gradients downwind of a highway. However, rarely do mobile monitoring studies report the sensitivity of their results to the chosen data processing approaches. The study being reported here utilized a large mobile monitoring dataset collected on a roadway network in central North Carolina to explore common data processing strategies including time-alignment, short-term emissions event detection, background estimation, and averaging techniques. One-second time resolution measurements of ultrafine particles ≤ 100 nm in diameter (UFPs), black carbon (BC), particulate matter (PM), carbon monoxide (CO), carbon dioxide (CO2), and nitrogen dioxide (NO2) were collected on twelve unique driving routes that were repeatedly sampled. Analyses demonstrate that the multiple emissions event detection strategies reported produce generally similar results and that utilizing a median (as opposed to a mean) as a summary statistic may be sufficient to avoid bias in near-source spatial trends. Background levels of the pollutants are shown to vary with time, and the estimated contributions of the background to the mean pollutant concentrations were: BC (6%), PM2.5–10 (12%), UFPs (19%), CO (38%), PM10 (45%), NO2 (51%), PM2.5 (56%), and CO2 (86%). Lastly, while temporal smoothing (e.g., 5 s averages) results in weak pair-wise correlation and the blurring of spatial trends, spatial averaging (e.g., 10 m) is demonstrated to increase correlation and refine spatial trends.

This is the standard operating procedure used by the Isotope Ratio Mass Spectrometry Group of the Chemical Sciences Division at LLNL for the preparation of a sample of uranium oxide or uranium metal for {sup 230}Th-{sup 234}U age-dating. The method described here includes the dissolution of a sample of uranium oxide or uranium metal, preparation of a secondary dilution, spiking of separate aliquots for uranium and thorium isotope dilution measurements, and purification of uranium and thorium aliquots for mass spectrometry. This SOP may be applied to uranium samples of unknown purity as in a nuclear forensic investigation, and also to well-characterized samples such as, for example, U{sub 3}O{sub 8} and U-metal certified reference materials. The sample of uranium is transferred to a quartz or PFA vial, concentrated nitric acid is added and the sample is heated on a hotplate at approximately 100 C for several hours until it dissolves. The sample solution is diluted with water to make the solution approximately 4 M HNO{sub 3} and hydrofluoric acid is added to make it 0.05 M HF. A secondary dilution of the primary uranium solution is prepared. Separate aliquots for uranium and thorium isotope dilution measurements are taken and spiked with {sup 233}U and {sup 229}Th, respectively. The spiked aliquot for uranium isotope dilution analysis is purified using EiChrom UTEVA resin. The spiked aliquot for thorium isotope dilution analysis is purified by, first, a 1.8 mL AG1x8 resin bed in 9 M HCl on which U adsorbs and Th passes through; second, adsorbing Th on a 1 mL AG1x8 resin bed in 8 M HNO{sub 3} and then eluting it with 9 M HCl followed by 0.1 M HCl + 0.005 M HF; and third, by passing the Th through a final 1.0 mL AG1x8 resin bed in 9 M HCl. The mass spectrometry is performed using the procedure 'Th and U Mass Spectrometry for {sup 230}Th-{sup 234}U Age Dating'.

We present the first measurement of the left-right cross section asymmetry (${\mathit{A}}_{\mathit{L}\mathit{R}}$) for Z boson production by ${\mathit{e}}^{+}$${\mathit{e}}^{\mathrm{\ensuremath{-}}}$ collisions. The measurement was performed at a center-of-mass energy of 91.55 GeV with the SLD detector at the SLAC Linear Collider which utilized a longitudinally polarized electron beam. The average beam polarization was (22.4\ifmmode\pm\else\textpm\fi{}0.6)%. Using a sample of 10 224 Z decays, we measure ${\mathit{A}}_{\mathit{L}\mathit{R}}$ to be 0.100\ifmmode\pm\else\textpm\fi{}0.044(stat)\ifmmode\pm\else\textpm\fi{}0.004(syst), which determines the effective weak mixing angle to be ${\mathrm{sin}}^{2}$${\mathrm{\ensuremath{\theta}}}_{\mathit{W}}^{\mathit{e}\mathit{f}\mathit{f}}$=0.2378 \ifmmode\pm\else\textpm\fi{}0.0056(stat)\ifmmode\pm\else\textpm\fi{}0.0005(syst).

We used short lived {sup 239}Np as a yield tracer and state of the art magnetic sector ICP-MS to measure ultra low levels of {sup 237}Np in a number of 'hot wells' at the Nevada National Security Site (NNSS), formerly known as the Nevada Test Site (NTS). The results indicate that {sup 237}Np concentrations at the Almendro, Cambric, Dalhart, Cheshire and Chancellor sites, are in the range of 3 x 10{sup -5} to 7 x 10{sup -2} pCi/L and well below the MCL for alpha emitting radionuclides (15 pCi/L) (EPA, 2009). Thus, while Np transport is believed to occur at the NNSS, activities are expected to be well below the regulatory limits for alpha-emitting radionuclides. We also compared {sup 237}Np concentration data to other radionuclides, including tritium, {sup 14}C, {sup 36}Cl, {sup 99}Tc, {sup 129}I, and plutonium, to evaluate the relative {sup 237}Np transport behavior. Based on isotope ratios relative to published unclassified Radiologic Source Terms (Bowen et al., 1999) and taking into consideration radionuclide distribution between melt glass, rubble and groundwater (IAEA, 1998), {sup 237}Np appears to be substantially less mobile than tritium and other non-sorbing radionuclides, as expected. However, this analysis also suggests that {sup 237}Np mobility ismore » surprisingly similar to that of plutonium. The similar transport behavior of Np and Pu can be explained by one of two possibilities: (1) Np(IV) and Pu(IV) oxidation states dominate under mildly reducing NNSS groundwater conditions resulting in similar transport behavior or (2) apparent Np transport is the result of transport of its parent {sup 241}Pu and {sup 241}Am isotopes and subsequent decay to {sup 237}Np. Finally, measured {sup 237}Np concentrations were compared to recent Hydrologic Source Term (HST) models. The 237Np data collected from three wells in Frenchman Flat (RNM-1, RNM-2S, and UE-5n) are in good agreement with recent HST transport model predictions (Carle et al., 2005). The agreement provides confidence in the results of the predictive model. The comparison to Cheshire HST model predictions (Pawloski et al, 2001) is somewhat ambiguous due to the low concentration resolution of the particle transport model.« less

The effect of temperature on the intensity of X-ray reflexion by gold, copper and aluminium has been studied by making microphotometric measurements on lines in X-ray structure spectra obtained with powder specimens in a Debye-Scherrer camera. A special method was employed to make cylindrical powder specimens, 0.8 mm. in diameter, which held together without adhesive and were free from a core of foreign material. The primary beam was standardized by means of a flat-plate X-ray camera, furnished with a plate of powdered gold which provided a spectrum whose lines could be accurately measured. The powder specimen under investigation was maintained in vacuo at temperatures ranging up to about 900° K, and its temperature estimated from lattice parameter measurements. The observed fall in intensity of X-ray reflexion by gold and copper as the temperature is raised up to about 900° K can be accounted for if the characteristic temperature varies with temperature in accordance with the relation θ T = θ 1 [1 ─ αγ( T ─ T 1 )], where θ T and θ 1 are the characteristic temperatures at temperatures T and T 1 , α is the cubical coefficient of thermal expansion and γ is the Grȕneisen constant. This relation is found to hold also for aluminium up to about 600° K. Beyond 600° K the fall of intensity exceeds that to be expected from the above relation, and it is suggested that another factor becomes prominent in the case of aluminium at the higher temperatures. The characteristic temperatures of gold, copper and aluminium now found by X-ray measurement at different temperatures, agree with the values obtained at those temperatures by specific heat and electrical conductivity methods.

A study of prompt neutrino events from 400 GeV protons on a beam-dump is presented. The ratio of electron- to muon-neutrino rates is 0.86±0.14, in agreement withe−μ universality. The anti-neutrino to neutrino flux ratio is $$\bar v_\mu /v_\mu = 0.81 \pm 0.19$$ . The absolute rates and distributions observed are shown to be in quantitative agreement with the known properties of charmedquark production in hadron collisions.

In 2004, a borehole was drilled into the 1983 Chancellor underground nuclear test cavity to investigate the distribution of radionuclides within the cavity. Sidewall core samples were collected from a range of depths within the re-entry hole and two sidetrack holes. Upon completion of drilling, casing was installed and a submersible pump was used to collect groundwater samples. Test debris and groundwater samples were analyzed for a variety of radionuclides including the fission products {sup 99}Tc, {sup 125}Sb, {sup 129}I, {sup 137}Cs, and {sup 155}Eu, the activation products {sup 60}Co, {sup 152}Eu, and {sup 154}Eu, and the actinides U, Pu, and Am. In addition, the physical and bulk chemical properties of the test debris were characterized using Scanning Electron Microscopy (SEM) and Electron Microprobe measurements. Analytical results were used to evaluate the partitioning of radionuclides between the melt glass, rubble, and groundwater phases in the Chancellor test cavity. Three comparative approaches were used to calculate partitioning values, though each method could not be applied to every nuclide. These approaches are based on: (1) the average Area 19 inventory from Bowen et al. (2001); (2) melt glass, rubble, and groundwater mass estimates from Zhao et al. (2008); and (3) fission product mass yield data from England and Rider (1994). The U and Pu analyses of the test debris are classified and partitioning estimates for these elements were calculated directly from the classified Miller et al. (2002) inventory for the Chancellor test. The partitioning results from this study were compared to partitioning data that were previously published by the IAEA (1998). Predictions of radionuclide distributions from the two studies are in agreement for a majority of the nuclides under consideration. Substantial differences were noted in the partitioning values for {sup 99}Tc, {sup 125}Sb, {sup 129}I, and uranium. These differences are attributable to two factors: chemical volatility effects that occur during the initial plasma condensation, and groundwater remobilization that occurs over a much longer time frame. Fission product partitioning is very sensitive to the early cooling history of the test cavity because the decay of short-lived (t{sub 1/2} < 1 hour) fission-chain precursors occurs on the same time scale as melt glass condensation. Fission product chains that include both volatile and refractory elements, like the mass 99, 125, and 129 chains, can show large variations in partitioning behavior depending on the cooling history of the cavity. Uranium exhibits similar behavior, though the chemical processes are poorly understood. The water temperature within the Chancellor cavity remains elevated (75 C) more than two decades after the test. Under hydrothermal conditions, high solubility chemical species such as {sup 125}Sb and {sup 129}I are readily dissolved and transported in solution. SEM analyses of melt glass samples show clear evidence of glass dissolution and secondary hydrothermal mineral deposition. Remobilization of {sup 99}Tc is also expected during hydrothermal activity, but moderately reducing conditions within the Chancellor cavity appear to limit the transport of {sup 99}Tc. It is recommended that the results from this study should be used together with the IAEA data to update the range in partitioning values for contaminant transport models at the Nevada National Security Site (formerly known as the Nevada Test Site).

A high-statistics measurement of the differential cross-sections for neutrino-iron scattering in the wide-band neutrino beam at the CERN SPS is presented. Nucleon structure functions are extracted and theirQ 2 evolution is compared with the predictions of quantum chromodynamics.

Hansson, L., and H. Hentonen. 1985. Gradients in density variation of small rodents: the importance of latitude and snow cover. Oecologia 67:394-402. Haukioja, E., S. Neuvonen, S. Hanhimaki, and P. Niemeli. 1988. The autumnal moth in Fennoscandia. Pages 163-178 in A. A. Berryman, editor. Dynamics of forest insect populations: patterns, causes, implications. Plenum, New York, New York, USA. Holling, C. S. 1965. The functional response of predators to prey density and its role in mimicry and population regulation. Memoirs of the Entomological Society of Canada 45:5-60. Mason, R. R., and B. E. Wickman. 1988. The Douglas-fir tussock moth in the interior Pacific Northwest. Pages 179209 in A. A. Berryman, editor. Dynamics of forest insect populations: patterns, causes, implications. Plenum, New York, New York, USA. Montgomery, M. E., and W. E. Wallner. 1988. The gypsy moth: a westward migrant. Pages 353-375 in A. A. Berryman, editor. Dynamics of forest insect populations: patterns, causes, implications. Plenum, New York, New York, USA. Morris, R. F 1959. Single factor analysis in population dynamics. Ecology 40:580-588. Munster-Swendsen, M. 1985. A simulation study of primary-, cleptoand hyperparasitism in Epinotia tedella (Lepidoptera, Tortricidae). Journal of Animal Ecology 54: 683-695. Royama, T. 1977. Population persistence and density dependence. Ecological Monographs 47:1-35. . 1981. Fundamental concepts and methodology for the analysis of animal population dynamics, with particular reference to univoltine insects. Ecological Monographs 51: 473-493. . 1992. Analytical population dynamics. Chapman & Hall, Oxford, England. Turchin, P. 1990. Rarity of density dependence or population regulation with lags? Nature 344:660-663. . 1991. Nonlinear modeling of time series data: limit cycles and chaos in forest insects, voles, and epidemics. Pages 39-62 in J. A. Logan and F P. Hain, editors. Chaos and insect ecology. Virginia Experiment Station Information Series 91-3. Virginia Experiment Station, Blacksburg, Virginia, USA. . 1993. Chaos and stability in rodent population dynamics: evidence from nonlinear time series analysis. Oikos 68:167-172. Turchin, P., and A. D. Taylor. 1992. Complex dynamics in ecological time series. Ecology 73:289-305. Williams, D. W., and A. M. Liebhold. 1995. Detection of delayed density dependence: effects of autocorrelation in an exogenous factor. Ecology 76:1005-1008.

This procedure gives the methods used at LLNL for the purification of uranium and plutonium from bulk environmental samples provided by the IAEA through the DOE Network of Analytical Laboratories (NWAL).

This procedure is written as general guidance for the measurement of elemental isotopic composition by plasma-source inorganic mass spectrometry. Analytical methods for uranium and plutonium are given as examples.

Synthetic ion beams with instantaneous and temporal characteristics appropriate to thermal ionization mass spectrometry (TIMS) were mathematically generated and analyzed to determine the effects of using a mixed {sup 233}U-{sup 236}U spike (double-spike) in the analysis of uranium isotopes. The instantaneous beam characteristics are the intensities (e.g., counts per second) modeled with a Poisson distribution plus a component of random noise that simulates the detection processes. Several beam intensity and mass fractionation vs. time functions were modeled to simulate a range of sample sizes and the commonly employed methods of data collection. These beam profiles were also generated with different noise levels, and signal-to-noise vs. analytical precision diagrams are presented. Modeling focused on natural uranium, where {sup 238}U/{sup 235}U = 137.88, and on the ability of a given method to determine precisely and accurately small variations in this ratio. Practical limits on precision were determined to be 20-30 ppm, which is consistent with precision seen for other elements by state-of-the-art TIMS. The TIMS total evaporation method was compared directly with the double-spike method. While similar analytical precisions are obtained with either method, the double-spike method of correcting for analytical bias gives more accurate results. The results of a total evaporationmore » analysis will deviate from true by more than the analytical precision if as little as 0.05% of the signal is not integrated, whereas the accuracy and precision of the double-spiked analyses are always linked.« less

CWeblog is a web and palm OS-based system used by medical students to record the problems and diagnoses of patients encountered in third-year clerkships at the Uniformed Services University. Data is available for analysis by clerkship directors as soon as it is entered. A pretest is given on the first day of the internal medicine third-year clerkship (the clerkship), and the National Board of Medical Examiners shelf examination (NBME) is given during the final twelfth week. Internal medicine specialty societies publish a list of 20 core problems in internal medicine to be emphasized during the third-year clerkship.

More than ten large-scale mutagenesis projects are now generating hundreds of novel mouse mutants. Projects employ a wide variety of strategies and screens: targeting as much as the whole genome, part of a chromosome or just single genes. In this commentary, we consider the pros and cons of different tactics. We highlight issues of cost, efficiency and defend the impact of this mutagenesis program in an era of sophisticated conditional knockouts and advanced transgenic lines. Given the significant difficulties of adequately phenotyping and mapping randomly generated mutations that cover the whole genome, we tend to favor regional and gene-targeted screens. Whatever the choice of method, whole genome sequence data combined with detailed transcriptome and proteome surveys promise to significantly improve the efficiency with which series of mutations in a large subset of mammalian genes can be generated and cloned.

We recently mapped two quantitative trait loci that have widespread effects on hippocampal architecture in mouse: Hipp1a and Hipp5a. We also noted remarkable strain differences in the relative sizes of different hippocampal regions. Estimated heritable variation for these differences was 42% in hippocampus proper, 40% in dentate gyrus, 31% in granule cell layer and 18% in pyramidal cell layer. Region size varied at least 50% from largest to smallest measurement. Here we have utilized these differences to identify loci with effects on the dentate gyrus, granule cell layer, hippocampus proper and pyramidal cell layer. Our sample consists of C57BL/6J and DBA/2J and 32 BXD recombinant inbred strains. Volumetric data were corrected for shrinkage and for differences in brain weight. We identified significant loci on chromosomes (Chr) 6, 13 and 15, and a significant interaction locus on proximal Chr 11. A suggestive distal Chr 1 locus overlaps with Hipp1a. HipV13a (Chr 13, 42-78Mb) has an additive effect of 0.56 mm3 (12.1%) on dentate gyrus volume, while GrV6a (Chr 6, 29-65 Mb) has additive effects of 0.14 mm3 (16.0%) on the volume of the granule cell layer. HipV13a also interacts with DGVi11a, a locus on proximal Chr 11 that operates exclusively through its epistatic effect on HipV13a and has no independent main effect HipV15a (Chr 15, 0-51 Mb) has an additive effect of 1.76 mm3 (9.0%) on the volume of the hippocampus proper. We used WebOTL, a recently described web-based tool, to examine genetic correlation of gene expression with hippocampal volume. We identified a number of genes that map within the OTL intervals and have highly correlated expression patterns. Using WebQTL's extensive database of published BXD phenotypes, we also detected a strong and potentially biologically meaningful correlation between hippocampal volume and the acoustic startle response.

Objective:\ud To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.\ud \ud Design:\ud Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.\ud \ud Setting:\ud European clinical gynecology centers.\ud \ud Patient(s):\ud Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.\ud \ud Intervention(s):\ud Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.\ud \ud Main Outcome Measure(s):\ud Amenorrhea, fibroid volume, endometrial histology.\ud \ud Result(s):\ud After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2–6 days). Median fibroid volume change was −45% (interquartile range, −66%; −25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were −63%, −67%, and −72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.\ud \ud Conclusion(s):\ud Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids.

The retinoic acid receptors are expressed from early stages of development in the diverse tissues that make up the vertebrate eye. Their loss has subtle effects on eye development. We adapted sensitive quantitative trait locus (QTL) mapping methods to assess consequences of inactivating alleles of the alpha and beta receptors, Rara and Rarb, on eye and retinal development. Rara is of particular interest because this gene is a candidate for Nnc1, a QTL that controls retinal ganglion cell proliferation.We studied lines of mice in which expression of the a1 isoform of Rara or all isoforms of Rarb had been disrupted by gene targeting. We measured eye weight, lens weight, retinal area, and retinal ganglion cell number in each of six genotypes (Rara and Rarb -/-, +/-, +/+; 10-25 cases/genotype).Loss of either protein is associated with a small but significant loss of eye weight and retinal area. However, only the Rarb knockout has a significant effect on the ganglion cell population and the loss of both wildtype alleles leads to an 8,000 cell deficit. Surprisingly, loss of the Rara a1 isoform that is expressed in this cell population from early stages has no effect on number. Null alleles of both genes have little if any effect on lens growth.Despite its expression in embryonic retina, Rara is unlikely to be the Nnc1 QTL. In contrast, Rarb, a gene that maps to Chr 14 and which is not an Nnc1 candidate gene, has a significant effect on cell number and is therefore a QTL controlling this key population. This raises the intriguing possibility that normal allelic variants of Rarb modulate the ganglion cell population in other vertebrates, including humans.

Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p.05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.

Background Recombinant inbred (RI) strains of mice are an important resource used to map and analyze complex traits. They have proved particularly effective in multidisciplinary genetic studies. Widespread use of RI strains has been hampered by their modest numbers and by the difficulty of combining results derived from different RI sets. Results We have increased the density of typed microsatellite markers two- to five-fold in each of several major RI sets that share C57BL/6 as a parental strain (AXB, BXA, BXD, BXH and CXB). A common set of 490 markers was genotyped in just over 100 RI strains. Genotypes of around 1,100 additional microsatellites in one or more RI sets were generated, collected and checked for errors. Consensus RI maps that integrate genotypes of approximately 1,600 microsatellite loci were assembled. The genomes of individual strains typically incorporate 45-55 recombination breakpoints. The collected RI set - termed the BXN set - contains approximately 5,000 breakpoints. The distribution of recombinations approximates a Poisson distribution and distances between breakpoints average about 0.5 centimorgans (cM). Locations of most breakpoints have been defined with a precision of < 2 cM. Genotypes deviate from Hardy-Weinberg equilibrium in only a small number of intervals. Conclusions Consensus maps derived from RI strains conform almost exactly to theoretical expectation and are close to the length predicted by the Haldane-Waddington equation (x3.6 for a 2-3 cM interval between markers). Non-syntenic associations between different chromosomes introduce predictable distortions in quantitative trait locus (QTL) datasets that can be partly corrected using two-locus correlation matrices.

Various inbred strains of mice show different daily amounts of slow-wave sleep (SWS) and rapid-eye movement sleep (REMS), suggesting the possibility of genetic influences on sleep propensity. Previous work by others studying the spontaneous sleep patterns of seven strains of CXB recombinant inbred (RI) mice suggested several candidate quantitative trait loci (QTLs) associated with variation in REMS. Extending this approach, we evaluated the sleep patterns of 13 CXB RI strains and conducted linkage analyses based on 223 discrete informative loci. The probability density distribution of light phase REMS for the CXB RI strains showed deflections that correspond approximately to the parental phenotypes. This type of pattern is consistent with the presence of a low number of major effect quantitative trait loci. Regions of chromosomes 4, 16, and 17 showed provisional linkage to strain variation in REMS. The distribution of loci further suggested that dark phase and light phase REMS may be regulated by different genetic factors. Probabilities of linkage were not sufficient for declaration of a quantitative trait locus for REMS but were sufficient to warrant further analysis either with additional RI strains or with F2 panels.

Influenza-infected C57BL/6J mice spend increased amounts of time in slow-wave sleep (SWS) during the dark phase of the circadian cycle compared to healthy mice. In contrast, infected BALB/cByJ mice show a normal or reduced time in SWS, particularly during the light phase. To identify genetic loci with linkage to these traits, we measured sleep in 13 CXB recombinant inbred (RI) strains derived from a cross between C57BL/6ByJ and BALB/cByJ mice. The probability density distribution of sleep patterns of influenza-infected CXB RI mice showed modes that correspond roughly with the parental modes during the dark phase of the circadian cycle and are intermediate or C57BL/6-like during the light phase. These patterns are consistent with the presence of a low number of major effect quantitative trait loci (QTLs). Chromosomal regions with provisional association to strain variation in influenza-induced SWS patterns were identified. In particular, a 10- to 12-cM interval on Chr 6 between D6Mit74 and D6Mit188 contains a QTL (LRS = 16.6 at 1 cM proximal to D6Mit316; genomewide p.05) that influences the SWS response to influenza infection during the light phase. We have provisionally named this QTL Srilp1 (sleep response to influenza, light phase 1). Candidate genes for mediation of this phenotype include Ghrhr (growth hormone releasing hormone receptor), Crhr2 (corticotropin releasing hormone receptor 2), and Cd8a (an epitope on cytotoxic T lymphocytes). Several other intervals achieved suggestive probability scores that are sufficient to warrant further analysis either with additional RI strains or with F2 panels. The analysis also suggests that dark phase and light phase responses are regulated by different genetic factors.

Recent studies have identified genes that influence the length of the circadian period maintained by mice housed under constant lighting conditions. However, a less studied circadian activity variable is the amplitude of daily oscillations in locomotor activity. This parameter reflects spontaneous activity exhibited under standard lighting and housing conditions and, therefore, differs conceptually from assessments of exploratory or open-field activity, voluntary wheel-running, or circadian period during exposure to constant light or constant darkness conditions. We recently observed a greater daily amplitude of oscillation in spontaneous locomotor activity in C57BL/6 mice compared to BALB/cBy mice. To identify genetic loci with potential linkage to circadian variation in the amount of locomotor activity, we measured the spontaneous activity of 13 CXB recombinant inbred (RI) strains of mice. The probability density distributions of locomotor activity phenotypes for the 13 CXB RI strains were consistent with the presence of a low number of major quantitative trait loci affecting this trait. Regions of chromosomes 3, 8, 12, 13, and 19 showed provisional linkage to strain variation in locomotor activity. Probabilities of linkage were not sufficient for declaration of an activity-related quantitative trait locus but were sufficient to warrant further analysis either with additional RI strains or with F2 panels.

The U.S. EPA has conducted an evaluation of a commercially available lightweight fine particle personal sampler for use in human exposure and biomarker studies involving 24-h collections of particulate matter, particle-bound organics such as polycyclic aromatic hydrocarbons (PAHs), and semivolatile organics (PAHs). Independent laboratory evaluation of the prototype design, intended to produce a 2.5-micron aerodynamic diameter cut-point at a flow between 1.5 and 1.7 lpm (liters per minute), indicated that at a challenge flow rate of 1.5 lpm, the sampler provided an aerodynamic cut-point (dp50) of only 1.7 microns. The variance between expected size selection resulted from the prototype's jet diameter dimension being inadvertently based upon a flow rate of 2.0 lpm rather than an intended 1.5-1.7 lpm. Other aerodynamic factors not presently accounted for may also have played an influence. Extrapolated cut-points for flow rates at 1 and 3 lpm for the prototype were determined to be 2.1 and 1.2 microns, respectively. Total losses attributed to unwanted particle retention within the sampler ranged from 10% for 0.91 micron size particles to essentially zero approaching diameters greater than 2.0 microns. The ambient concentration of particles (1.7 microns) needed for acceptable gravimetric filter measurements involving 24-h sample collection was determined to be 10 micrograms/m3. Investigation of the sampler to retain and recover PAHs using XAD-2 resin, often of importance in human exposure biomarker studies, indicated that corrected recoveries between 94% and 108% could be obtained for 16 priority pollutant PAH species. Overall evaluation of the personal monitor indicates that it has research utility due to its modular features and size but reconfiguration should be performed that would permit true PM2.5 size selection. The current configuration collects particles less than 2.5 microns at approximately 95% collection efficiency.

Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped.Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J.Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2.Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.

Population models have suggested that host regulation by natural enemies is achieved by the densitydependent response of natural enemies to temporal and spatial changes in host density. However, surveys of insect host-parasitoid systems (Morrison and Strong 1980, Dempster 1983, Stiling 1987) indicate that few field studies provide unambiguous evidence of densitydependent relationships. It has been argued that density dependence may be obscured by various behavioral and stochastic elements involved in the interaction, rendering our methods for its detection inadequate (Morrison and Strong 1980, Stiling and Strong 1982, Hassell 1985, Lessels 1985, Morrison 1986, Stiling 1987, Price 1988). Hassell (1985) has suggested that the regulatory role of natural enemies may be detected by examining the relationship between the per capita searching efficiency and parasitoid density. The per capita searching efficiency is calculated as

Ovarian surface epithelial (OSE) cells participate in the formation of the ovarian cortex and are potential targets of oestrogen action. Oestrogens typically act through nuclear oestrogen receptors (ER) of which there are two known subtypes: ERalpha and ERbeta. In view of the potential importance of oestrogen as a local regulator of OSE cell function, we screened for ERalpha and ERbeta mRNA in primary OSE cell cultures by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, and used freshly isolated granulosa cells (GC) and granulosa-lutein cells (GLC) as positive controls. OSE cells, scraped from the ovarian surface of women undergoing laparotomy for benign gynaecological conditions, were cultured for up to 21 days to obtain enough cells for mRNA extraction. GC were obtained from spontaneously cyclic women undergoing total hysterectomy; while GLC were obtained from follicular aspirates of gonadotrophin-stimulated in-vitro fertilization patients. Total RNA (1 microg) was reverse transcribed into single-stranded cDNA for PCR (30 cycles) using primers selected to give specific ERalpha and ERbeta products. The ERalpha and ERbeta PCR products, authenticated by cloning and sequencing, were both weakly detectable by Southern analysis in cultured OSE cells and readily detectable in GC and GLC. These results show that cultured human OSE express both ERalpha and ERbeta mRNA, consistent with a role for oestrogen in the regulation of OSE cell function in vivo.

Personal exposure monitoring was conducted for road paving workers in three states. A research objective was to characterize and compare occupational exposures to fine respirable particles (2.5 microns) and particle-bound polycyclic aromatic hydrocarbons (PAHs) for road paving workers applying conventional (petroleum derived) asphalt and asphalt containing crumb rubber from shredded tires. Workers not exposed to asphalt fume were also included for comparison (to support the biomarker component of this study). The rubber content of the crumb rubber modified (CRM) asphalt at the three study sites was 12, 15, and 20%. A comparison of some specific job categories from two sites indicates greater potential carcinogenic PAH exposures during CRM asphalt work, however, the site with the greatest overall exposures did not indicate any differences for specific jobs. A statistical analysis of means for fine particle, pyrene and total carcinogenic PAH personal exposure shows, with two exceptions, there were no differences in exposures for these three measurement variables. One site shows significantly elevated pyrene exposure for CRM asphalt workers and another site similarly shows greater carcinogenic PAH exposure for CRM asphalt workers. Conventional and CRM asphalt worker airborne exposures to the PAH carcinogen marker, BaP, were very low with concentrations comparable to ambient air in many cities. However, this study demonstrates that asphalt road paving workers are exposed to elevated airborne concentrations of a group of unknown compounds that likely consist of the carcinogenic PAHs benz(a)anthracene, chrysene and methylated derivatives of both. The research described in this article has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

Searches for supersymmetric particles in channels with one or more photons and missing energy have been performed with data collected by the ALEPH detector at LEP. The data consist of 11.1 pb-1 at sqrt(s)=161 GeV, 1.1 pb-1 at 170 GeV and 9.5 pb-1 at 172 GeV. The e+e--->νν¯γ(γ) cross section is measured. The data are in good agreement with predictions based on the Standard Model, and are used to set upper limits on the cross sections for anomalous photon production. These limits are compared to two different SUSY models and used to set limits on the neutralino mass. A limit of 71 GeV/c2 at 95% C.L. is set on the mass of the lightest neutralino (τχ10

The autosomal semidominant mutation Bst (belly spot and tail) is often associated with small and atrophic optic nerves in adult mice and shares several important attributes with heritable optic nerve atrophy in humans. In this article, the authors present adult and developmental studies on the retinal phenotype in Bst/+ mice.Retinal ganglion cells in adult Bst/+ mice were labeled retrogradely with horseradish peroxidase injected into the right optic tract. Labeled ganglion cells were mapped in whole-mounted retinas ipsilateral and contralateral to the injection site. The number of axons in optic nerves of these and other cases were quantified using an electron microscopic method. Eyes of neonatal, embryonic day 15 (E15), and embryonic day 12 (E12) Bst/+ mutants were examined histologically to understand the etiology of the retinal phenotype.Approximately 60% of adult Bst/+ mice have deficient direct pupillary light responses. This neurologic phenotype is associated with a reduction in the number of retinal ganglion cells from the wild-type average of 67,000 to less than 20,000 in Bst/+ mutants. Ganglion cells with crossed projections are more severely affected than those with uncrossed projections. Histologic analysis of eyes from E12 mice reveals a delayed closure of the optic fissure. Despite this abnormality, other ocular structures appear relatively normal. However, some E15 mutants exhibit marked disorganization of the retinal neuroepithelium, and ganglion cell axons are found between pigmented and neural retina. At birth, optic nerves of affected mice are smaller than those of wild-type mice, ectopic axons are found within the eyes, and the ganglion cell layer contains many dying cells.The expression of the retinal phenotype in Bst/+ mutants is highly variable-ranging from a complete absence of ganglion cells to numbers comparable to that in wild-type mice. The reduction in ganglion cell number in affected adult Bst/+ mice is attributable to the failure of ganglion cell axons to reach the optic nerve head early in development. Delayed fusion of the fissure is consistently associated with the Bst/+ genotype and probably contributes to the failure of ganglion cell axons to grow out of the eye.

Indirect limits on the mass of the lightest neutralino are derived from the results of searches for charginos, neutralinos, and sleptons performed with data taken by the ALEPH Collaboration at centre-of-mass energies near the Z peak and at 130 and 136 GeV. Within the context of the Minimal Supersymmetric Standard Model and when $M_{\tilde\nu}\ge 200$ GeV/c^2, the bound $M_\chi>12.8$ GeV/c^2 at the 95\% confidence level applies for any $\tan\beta$. The impact of lighter sneutrinos is presented in the framework of SUSY grand unified theories; a massless neutralino is allowed only for a narrow range of $\tan\beta$, $\mu$, and the scalar mass parameter $m_0$. Finally, by including Higgs mass constraints and requiring that radiative electroweak symmetry breaking occur, more stringent bounds on $M_\chi$ as a function of $\tan\beta$ are derived., Comment: 26 pages, one latex file and 15 eps figures

Searches for charginos and neutralinos produced in e+e- collisions at centre-of-mass energies of 130 and 136 GeV have been performed under the assumptions that R-parity is not conserved, that the dominant R-parity violating coupling involves only leptonic fields, and that the lifetime of the lightest supersymmetric particle can be neglected. In the 5.7 pb-1 data sample collected by ALEPH, no candidate events were found. As a result, chargino and neutralino masses and couplings are constrained and the domains previously excluded at LEP1 are extended.