Pregnancy status predicted using milk mid-infrared spectra from dairy cattle.

Accurate and timely pregnancy diagnosis is an important component of effective herd management in dairy cattle. Predicting pregnancy from Fourier-transform mid-infrared (FT-MIR) spectroscopy data is of particular interest because the data are often already available from routine milk testing. The purpose of this study was to evaluate how well pregnancy status could be predicted in a large data set of 1,161,436 FT-MIR milk spectra records from 863,982 mixed-breed pasture-based New Zealand dairy cattle managed within seasonal calving systems. Three strategies were assessed for defining the nonpregnant cows when partitioning the records according to pregnancy status in the training population. Two of these used records for cows with a subsequent calving only, whereas the third also included records for cows without a subsequent calving. For each partitioning strategy, partial least squares discriminant analysis models were developed, whereby spectra from all the cows in 80% of herds were used to train the models, and predictions on cows in the remaining herds were used for validation. A separate data set was also used as a secondary validation, whereby pregnancy diagnosis had been assigned according to the presence of pregnancy-associated glycoproteins (PAG) in the milk samples. We examined different ways of accounting for stage of lactation in the prediction models, either by including it as an effect in the prediction model, or by pre-adjusting spectra before fitting the model. For a subset of strategies, we also assessed prediction accuracies from deep learning approaches, utilizing either the raw spectra or images of spectra. Across all strategies, prediction accuracies were highest for models using the unadjusted spectra as model predictors. Strategies for cows with a subsequent calving performed well in herd-independent validation with sensitivities above 0.79, specificities above 0.91 and area under the receiver operating characteristic curve (AUC) values over 0.91. However, for these strategies, the specificity to predict nonpregnant cows in the external PAG data set was poor (0.002-0.04). The best performing models were those that included records for cows without a subsequent calving, and used unadjusted spectra and days in milk as predictors, with consistent results observed across the training, herd-independent validation and PAG data sets. For the partial least squares discriminant analysis model, sensitivity was 0.71, specificity was 0.54 and AUC values were 0.68 in the PAG data set; and for an image-based deep learning model, the sensitivity was 0.74, specificity was 0.52 and the AUC value was 0.69. Our results demonstrate that in pasture-based seasonal calving herds, confounding between pregnancy status and spectral changes associated with stage of lactation can inflate prediction accuracies. When the effect of this confounding was reduced, prediction accuracies were not sufficiently high enough to use as a sole indicator of pregnancy status.

Strategies for noise reduction and standardization of milk mid-infrared spectra from dairy cattle.

The use of Fourier-transform mid-infrared (FTIR) spectroscopy is of interest to the dairy industry worldwide for predicting milk composition and other novel traits that are difficult or expensive to measure directly. Although there are many valuable applications for FTIR spectra, noise from differences in spectral responses between instruments is problematic because it reduces prediction accuracy if ignored. The purpose of this study was to develop strategies to reduce the impact of noise and to compare methods for standardizing FTIR spectra in order to reduce between-instrument variability in multiple-instrument networks. Noise levels in bands of the infrared spectrum caused by the water content of milk were characterized, and a method for identifying and removing outliers was developed. Two standardization methods were assessed and compared: piecewise direct standardization (PDS), which related spectra on a primary instrument to spectra on 5 other (secondary) instruments using identical milk-based reference samples (n = 918) analyzed across the 6 instruments; and retroactive percentile standardization (RPS), whereby percentiles of observed spectra from routine milk test samples (n = 2,044,094) were used to map and exploit primary- and secondary-instrument relationships. Different applications of each method were studied to determine the optimal way to implement each method across time. Industry-standard predictions of milk components from 2,044,094 spectra records were regressed against predictions from spectra before and after standardization using PDS or RPS. The PDS approach resulted in an overall decrease in root mean square error between industry-standard predictions and predictions from spectra from 0.190 to 0.071 g/100 mL for fat, from 0.129 to 0.055 g/100 mL for protein, and from 0.143 to 0.088 g/100 mL for lactose. Reductions in prediction error for RPS were similar but less consistent than those for PDS across time, but similar reductions were achieved when PDS coefficients were updated monthly and separate primary instruments were assigned for the North and South Islands of New Zealand. We demonstrated that the PDS approach is the most consistent method to reduce prediction errors across time. We also showed that the RPS approach is sensitive to shifts in milk composition but can be used to reduce prediction errors, provided that secondary-instrument spectra are standardized to a primary instrument with samples of broadly equivalent milk composition. Appropriate implementation of either of these approaches will improve the quality of predictions based on FTIR spectra for various downstream applications.

Mating strategies to maximize genetic merit in dairy cattle herds.

The genetic merit of a herd is a key determinant in productivity for dairy farmers. However, making breeding decisions to maximize the rate of genetic gain can be complex because there is no certainty about which cows will become pregnant with a heifer calf. In this study, breeding worth (BrW) was used as a measure of genetic merit, and several mating strategies were evaluated. These strategies included randomly mating whole herds to the entire bull team, excluding low-ranked cows from producing replacement heifers, and nominating high-ranked cows to the most highly ranked bulls. Simulations were undertaken using 4 bull teams generated from bulls currently marketed in New Zealand and a selection of New Zealand dairy herds. Average replacement heifer BrW was calculated for 1,000 iterations of each combination of mating strategy, herd, and bull team (scenario). Variation in resulting average replacement heifer BrW within scenarios was due to random sampling of which cows became pregnant with a heifer calf. Relative to mating the whole herd to an entire bull team, excluding the lowest ranked cows from producing replacements resulted in the greatest increase in average replacement heifer BrW across all herds and bull teams, with a gain of approximately 0.4 BrW point for each 1% of cows excluded. Nominating top-ranking cows to the highest ranking bulls in the team had little effect (0.06-0.13 BrW increase for each 1% of top cows nominated) in improving BrW of replacement heifers. The number of top bulls nominated had a variable effect depending on the BrW spread of the entire bull team. Although excluding cows with the lowest BrW from producing replacement heifers is most effective for improving BrW, it is important to ensure that the number of heifers born is sufficient to replace cows leaving the herd. It is likely that optimal strategies for improving BrW will vary from farm to farm depending not only on the BrW structure of the herd, the bull team available, and the reproduction success on farm but also on farm management practices. This simulation study provides expected outcomes from a variety of mating strategies to allow informed decision making on farm.

Bovine mammary gland X chromosome inactivation.

X chromosome inactivation (XCI) is a process by which 1 of the 2 copies of the X chromosomes present in female mammals is inactivated. The transcriptional silencing of one X chromosome achieves dosage compensation between XX females and XY males and ensures equal expression of X-linked genes in both sexes. Although all mammals use this form of dosage compensation, the complex mechanisms that regulate XCI vary between species, tissues, and development. These mechanisms include not only varying levels of inactivation, but also the nature of inactivation, which can range from being random in nature to driven by parent of origin. To date, no data describing XCI in calves or adult cattle have been reported and we are reliant on data from mice to infer potential mechanisms and timings for this process. In the context of dairy cattle breeding and genomic prediction, the implications of X chromosome inheritance and XCI in the mammary gland are particularly important where a relatively small number of bulls pass their single X chromosome on to all of their daughters. We describe here the use of RNA-seq, whole genome sequencing and Illumina BovineHD BeadChip (Illumina, San Diego, CA) genotypes to assess XCI in lactating mammary glands of dairy cattle. At a population level, maternally and paternally inherited copies of the X chromosome are expressed equally in the lactating mammary gland consistent with random inactivation of the X chromosome. However, average expression of the paternal chromosome ranged from 10 to 90% depending on the individual animal. These results suggest that either the mammary gland arises from 1 or 2 stem cells, or a nongenetic mechanism that skews XCI exists. Although a considerable amount of future work is required to fully understand XCI in cattle, the data reported here represent an initial step in ensuring that X chromosome variation is captured and used in an appropriate manner for future genomic selection.

Morphology, ecology, and molecular biology of a new species of giant larvacean in the eastern North Pacific: Bathochordaeus mcnutti sp. nov.

Bathochordaeus mcnutti sp. nov. is described from the mesopelagic northeast Pacific Ocean (Monterey Bay, California, USA). Larvaceans in the genus Bathochordaeus are large, often abundant zooplankters found throughout much of the world ocean, but until recently it was unclear whether more than a single species of Bathochordaeus existed. Using remotely operated vehicles, we have made hundreds of in situ observations, compiled two decades of time-series data, and carefully collected enough specimens to determine that three species of Bathochordaeus occur in Monterey Bay: B. charon (Chun), B. stygius (Garstang), and B. mcnutti sp. nov. Bathochordaeus mcnutti is readily distinguished from its two congeners by the distinct blue outline visible around the periphery of its tail, and by other aspects of its morphology, ecology, and genetics. The abundance of larvaceans means they are ecologically important as particle processors. Species within the genus, Bathochordaeus, comprise the largest of described larvaceans.

Effect of prophylactic indomethacin administration and early feeding on spontaneous intestinal perforation in extremely low-birth-weight infants.

OBJECTIVE: To determine the effect of concomitant administration of prophylactic indomethacin and early enteral feeds on the risk of spontaneous intestinal perforation (SIP) in extremely low-birth-weight (ELBW) infants, and to describe the variation in prophylactic indomethacin use in Canada. STUDY DESIGN: A retrospective cohort study of 4268 ELBW infants born at <30 weeks' gestation admitted to Canadian neonatal units between 2010 and 2014 was conducted. Prophylactic indomethacin (I+ or I-, administered within 24 h) and early feeding (E+ or E-, initiated in the first 2 days) exposures were studied concurrently and independently. The primary outcomes were SIP and death before discharge. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Compared with the I-/E+ reference group (n=1829), infants in I+/E+ (n=285; aOR 2.92, 95% CI 1.41 to 6.08) and I+/E- (n=213; aOR 2.84, 95% CI 1.35 to 5.98) groups had higher odds of SIP, whereas those in the I-/E- group had similar odds (n=1941; aOR 1.37, 95% CI 0.88 to 2.14). Odds of SIP were higher in the indomethacin exposed group (I+) compared with the unexposed (I-) group when controlled for early feeding (aOR 2.43, 95% CI 1.41 to 4.19), but not in the early feeding group when controlled for indomethacin. The use of prophylactic indomethacin ranged from 0% usage in 13 sites to 78% use in one site. CONCLUSION: Prophylactic indomethacin was associated with increased odds of SIP independently from early feeding in this cohort; however, early enteral feeding was not associated with SIP. Marked variation in the use of prophylactic indomethacin was identified.

Precautionary allergen labelling: perspectives from key stakeholder groups.

Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counterproductive for consumers with food allergies. This review aims to summarize the perspectives of all the key stakeholders (including clinicians, patients, food industry and regulators), with the aim of defining common health protection and risk minimization goals. The lack of agreed reference doses has resulted in inconsistent application of PAL by the food industry and in levels of contamination that prompt withdrawal action by enforcement officers. So there is a poor relationship between the presence or absence of PAL and actual reaction risk. This has led to a loss of trust in PAL, reducing the ability of consumers with food allergies to make informed choices. The result has been reduced avoidance, reduced quality of life and increased risk-taking by consumers who often ignore PAL. All contributing stakeholders agree that PAL must reflect actual risk. PAL should be transparent and consistent with rules underpinning decision-making process being communicated clearly to all stakeholders. The use of PAL should indicate the possible, unintended presence of an allergen in a consumed portion of a food product at or above any proposed action level. This will require combined work by all stakeholders to ensure everyone understands the approach and its limitations. Consumers with food allergy then need to be educated to undertake individualized risk assessments in relation to any PAL present.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies.

An automated in-line clinical mastitis detection system using measurement of conductivity from foremilk of individual udder quarters.

AIM: To assess a novel method for automatic in-line detection of clinical mastitis. METHODS: For a brief period at the start of milking for each cow, electrical conductivity of foremilk was measured for each quarter in turn, using a single sensor installed in the long milk tube (LMT) about 1.5 m downstream from the milking-machine claw. Sequential separation of flow between udder quarters was achieved by control of pulsation to individual teat cups within a conventional cluster. The ratio of conductivity values between quarters was used as an indicator of mastitis status. The concept was evaluated initially in a pilot trial in a 200-cow herd milked in a 23-stall swing-over herringbone milking parlour. It was then tested rigorously in a field trial in a 640-cow herd milked in a 50-stall rotary milking parlour. Both trials were conducted in the Waikato region of New Zealand. In the latter trial, sensor results were compared with visual inspection of a commercial in-line mastitis filter fitted to each milking unit. These filters were inspected for clots immediately after every cow's milking, for 3 weeks. The dataset of approximately 27,000 individual milkings was tested against several published or potential alternative 'gold standards' for diagnosing clinical mastitis. RESULTS: In the pilot trial, 12-14 clinical events were detected out of 19 true clinical quarters, with a false-alert rate of between three and five false electrical-conductivity alerts per 1,000 individual milkings. In the more rigorous field trial, sensitivity ranged from 68 to 88%, and the false-alert rate (false-alert episodes per 1,000 individual milkings) ranged from 2.3 to 7.0. CONCLUSION: The novel clinical mastitis detection system, based on separation of the flow and measurement of electrical conductivity from foremilk of individual udder quarters, has the potential to provide a new tool for helping farmers to monitor clinical mastitis in herds milked with conventional clusters.

Automatic detection of clinical mastitis is improved by in-line monitoring of somatic cell count.

This study explored the potential value of in-line composite somatic cell count (ISCC) sensing as a sole criterion or in combination with quarter-based electrical conductivity (EC) of milk, for automatic detection of clinical mastitis (CM) during automatic milking. Data generated from a New Zealand research herd of about 200 cows milked by 2 automatic milking systems during the 2006-2007 milking season included EC, ISCC, monthly laboratory-determined SCC, and observed cases of CM that were treated with antibiotics. Milk samples for ISCC and laboratory-determined SCC were taken sequentially at the end of a cow milking. Both samples were derived from a composite cow milking obtained from the bottom of the milk receiver. Different time windows were defined in which true-positive, false-negative, and false-positive alerts were determined. Quarters suspected of having CM were visually checked and, if CM was confirmed, sampled for bacteriological culturing and treated with an antibiotic treatment. These treated quarters were considered as gold-standard positives for comparing CM detection models. Alert thresholds were adjusted to achieve a sensitivity of 80% in 3 detection models: using ISCC alone, EC alone, or a combination of these. The success rate (also known as the positive predictive value) and the false alert rate (number of false-positive alerts per 1,000 cow milkings) were used to evaluate detection performance. Normalized ISCC estimates were highly correlated with normalized laboratory-determined SCC measurements (r = 0.82) for SCC measurements >200 x 10(3) cells/mL. Using EC alone as a detection tool resulted in a range of 6.9 to 11.0% for success rate, and a range of 4.7 to 7.8 for the false alert rate. Values for the ISCC model were better than the model using EC alone with 12.7 to 15.6% for the success rate and 2.9 to 3.7 for the false alert rate. Combining sensor information to detect CM, by using a fuzzy logic algorithm, produced a 2- to 3-fold increase in the success rate (range 21.9 to 32.0%) and a 2- to 3-fold decrease in the false alert rate (range 1.2 to 2.1) compared with the models using ISCC or EC alone. Results suggest that the performance of a CM detection system improved when ISCC information was added to a detection model using EC information.

Long-term outcome after neonatal intraparenchymal echodensities with porencephaly.

OBJECTIVE: To compare long-term neurodevelopmental and functional outcomes of neonatal intensive care unit (NICU) survivors with neonatal intraparenchymal echodensities (IPE) with porencephaly on cranial ultrasonography with matched controls. To compare the developmental trajectories of these infants over the childhood years with those of matched controls. DESIGN: Cohort study. SETTING: Tertiary level NICU and the Neonatal Follow-Up Programme (NFUP) in Vancouver, Canada. PATIENTS: NICU survivors with birth weights <1250 g, born between 1983 and 1985. METHODS: Cranial ultrasound scans of NICU subjects with grade 4 intraventricular haemorrhage (IVH) were reviewed by a neuroradiologist and cases were defined, using stringent criteria, as IVH with IPE with porencephaly. Controls with normal cranial ultrasound findings were selected case-matched for birth weight and sex. Prospective sequential multidisciplinary assessments were performed up to 17 years in the NFUP. Mann-Whitney U test was used to compare outcomes between cases and controls. RESULTS: Of 385 eligible patients, 14 met IPE and porencephaly criteria and 10 survived to discharge. All cases with IPE and porencephaly had one or more impairments, significantly different from preterm controls (p<0.001). At all ages assessed, rates of motor, cognitive and overall impairment were significantly higher in the cases (p< or =0.002 for all tests). Most cases at adolescence were ambulatory, required learning assistance in school and had social challenges. CONCLUSIONS: Children with neonatal IPE and porencephaly have a much worse long-term neurodevelopmental outcome than children with normal cranial ultrasound findings.

Working mothers and early childhood outcomes: lessons from the Canadian National Longitudinal Study on Children and Youth.

BACKGROUND: More mothers are choosing to return to work during the first 2 years of their child's life with an uncertain impact on early developmental outcomes. AIMS: To determine the association between duration of maternity leave and motor and social development of toddlers. STUDY DESIGN: Population-based, retrospective cohort study. SUBJECTS: The Canadian National Longitudinal Survey on Children and Youth (NLSCY) Cycle 3 provides data on the characteristics and life experience of Canadian children. For sampled households, the person most knowledgeable about the child completed a survey on demographics, parent characteristics and family environment. The analysis was limited to 6664 families with children up to 2 years. OUTCOME MEASURES: Logistic regression was used to assess the association between duration of maternity leave and impaired performance (<-1 SD below the mean) on the Motor and Social Development (MSD) scale adjusted for multiple covariates including maternal age, gender, breastfeeding and socioeconomic status. RESULTS: One month of maternity leave increased the odds of impaired performance on the MSD by 3% (OR 1.03, 95% CI 1.02, 1.04). This was also seen with categorized maternity leave duration. Being male (OR 1.53, 95% CI 1.35, 1.74) and having a younger mother (OR 1.48, 95% CI 0.98, 2.23) increased the risk of impaired performance on the MSD while being of higher SES reduced the risk (OR 0.96, 95% CI 0.93, 1.00). CONCLUSIONS: There is an association between duration of maternity leave and impaired performance in motor and social development in children up to 2 years.

Neurodevelopmental sequelae of intraventricular haemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants.

BACKGROUND: Major grades of intraventricular haemorrhage (IVH) are associated with adverse neurodevelopmental sequelae in early childhood but the extent of problems in specific cognitive areas, such as executive function, and the contribution of lesser grades of IVH to neurodevelopmental problems at school age are not well described. AIMS: To determine the neuromotor, cognitive and educational outcome of extremely low birthweight (ELBW, birthweight <1000 g) or very preterm (<28 weeks) infants at 8 years of age related to the severity of IVH diagnosed in the newborn period. DESIGN: Regional cohort study. PATIENTS: Consecutive surviving children of either birthweight <1000 g or gestational age <28 weeks born in the state of Victoria in 1991 or 1992. MAIN OUTCOME MEASURES: Neurological impairments and disabilities, cognitive function and academic progress. RESULTS: Of 298 consecutive ELBW/very preterm survivors 270 (90.6%) with cranial ultrasound data were assessed at 8 years of age. Cerebral palsy, poor motor performance and major neurosensory disability were more prevalent with increasing severity of IVH. Cognitive functioning across domains was worse with increasing severity of IVH. Most of the differences were attributable to the few (n=6) survivors who had grade 4 IVH; there were few substantial differences between survivors with lesser grades of IVH. CONCLUSIONS: Neurodevelopmental dysfunction at school age in ELBW/very preterm survivors varies little with increasing severity of IVH, with the exception of grade 4 IVH.

Methods to adjust for the interference of N2O on delta13C and delta18O measurements of CO2 from soil mineralization.

In this paper we present an overview of the present knowledge relating to methods that avoid interference of N2O on delta13C and delta18O measurements of CO2. The main focus of research to date has been on atmospheric samples. However, N2O is predominantly generated by soil processes. Isotope analyses related to soil trace gas emissions are often performed with continuous flow isotope ratio mass spectrometers, which do not necessarily have the high precision needed for atmospheric research. However, it was shown by using laboratory and field samples that a correction to obtain reliable delta13C and delta18O values is also required for a commercial continuous flow isotope ratio mass spectrometer. The capillary gas chromatography column of the original equipment was changed to a packed Porapak Q column. This adaptation resulted in an improved accuracy and precision of delta13C (standard deviation(Ghent): from 0.2 to 0.08 per thousand; standard deviation(Lincoln): from 0.2 to 0.13 per thousand) of CO2 for N2O/CO2 ratios up to 0.1. For delta18O there was an improvement for the standard deviation measured at Ghent University (0.13 to 0.08 per thousand) but not for the measurements at Lincoln University (0.08 to 0.23 per thousand). The benefits of using the packed Porapak Q column compared with the theoretical correction method meant that samples were not limited to small N(2)O concentrations, they did not require an extra N2O concentration measurement, and measurements were independent of the variable isotopic composition of N2O from soil.

Cell interactions with laser-modified polymer surfaces.

The performance of a polymeric biomaterial depends on the bulk and surface properties. Often, however, the suitability of the surface properties is compromised in favour of the bulk properties. Altering the surface properties of these materials will have a profound effect on how cells and proteins interact with them. Here, we have used an excimer laser to modify the surface wettability of nylon 12. The surface treatment is rapid, cost-effective and can cause reproducible changes in the surface structure of the polymers. Polymers were treated with short wavelength ( < 200 nm) UV light. These wavelengths have sufficient photon energy (6.4eV) to cause bond scission at the material surface. This results in a surface reorganisation with incorporation of oxygen. Surface wettability changes were confirmed using contact angle measurements. Cell interactions with the surfaces were examined using 3T3 fibroblast and HUVEC cells. Cells morphology was examined using a confocal laser scanning microscope (CLSM). Cell activity and cell number on the treated nylon were assessed using biochemical assays for up to seven days. Both fibroblasts and endothelial cells initially proliferated better on treated compared with untreated samples. However, over seven days activity decreased for both cell types on the control samples and endothelial cell activity and cell number also decreased on the treated polymer.

Real-time, high-resolution quantitative measurement of multiple soil gas emissions: selected ion flow tube mass spectrometry.

A new technique is presented for the rapid, high-resolution identification and quantification of multiple trace gases above soils, at concentrations down to 0.01 microL L(-1) (10 ppb). The technique, selected ion flow tube mass spectrometry (SIFT-MS), utilizes chemical ionization reagent ions that react with trace gases but not with the major air components (N2, O2, Ar, CO2). This allows the real-time measurement of multiple trace gases without the need for preconcentration, trapping, or chromatographic separation. The technique is demonstrated by monitoring the emission of ammonia and nitric oxide, and the search for volatile organics, above containerized soil samples treated with synthetic cattle urine. In this model system, NH3 emissions peaked after 24 h at 2000 nmol m(-2) s(-1) and integrated to approximately 7% of the urea N applied, while NO emissions peaked about 25 d after urine addition at approximately 140 nmol m(-2) s(-1) and integrated to approximately 10% of the applied urea N. The monitoring of organics along with NH3 and NO was demonstrated in soils treated with synthetic urine, pyridine, and dimethylamine. No emission of volatile nitrogen organics from the urine treatments was observed at levels >0.01% of the applied nitrogen. The SIFT method allows the simultaneous in situ measurement of multiple gas components with a high spatial resolution of < 10 cm and time resolution <20 s. These capabilities allow, for example, identification of emission hotspots, and measurement of localized and rapid variations above agricultural and contaminated soils, as well as integrated emissions over longer periods.

How an audit of epidural patients in a community hospital setting resulted in the development of a formal acute pain management service.

PURPOSE: To describe the results of an audit of patients who received epidural analgesics postoperatively and the subsequent development of a formal acute pain management service in a community hospital. METHODS: To understand how epidural analgesia was being used to treat postoperative pain at the Peterborough Regional Health Centre, Peterborough, Ontario, a retrospective chart review was performed. Audits were performed on 178 patients who had received epidural analgesia postoperatively from October 1994 to May 1995. Data pertaining to demographics, epidural analgesia, pain scores and side effects were collected. RESULTS: Sixty-one per cent of patients received bupivacaine/ fentanyl infusions, and 39% received epidural morphine boluses. More than 60% of patients reported no pain postoperatively. Patients who received bupivacaine/fentanyl were more likely than those who received epidural morphine to also receive co-analgesia and transitional analgesia. Patients who received epidural morphine were more likely than those who received bupivacaine fentanyl to experience respiratory depression, hypotension and pruritus. Patients were followed by the anesthesiologist who provided the anesthetic. Anesthesiologists practised independently, and formal policies and procedures did not exist. CONCLUSIONS: As a result of the audit, an acute pain management service was developed. This included a team that did daily rounds and consisted of a nurse clinician and an anesthesiologist who was assigned to the service on a weekly basis. A committee was created, and formalized policies and procedures were established. Standardized order sheets, data sheets and a computerized database were developed. Reports for administrative and quality improvement purposes were generated monthly. Education programs were developed. Co-analgesia and transitional analgesia are now part of routine care, and epidural catheter placement close to the site of incision is encouraged. A postoperative nausea and vomiting algorithm, and a treatment regimen for pruritus have also been implemented.

Ethical issues in transgenics.

The arguments of critics and concerns of the public on generating transgenic cloned animals are analyzed for the absence or presence of logical structure. Critics' arguments are symbolically compared with "genetic trespassing," "genetic speeding," or "going the wrong way," and responses are provided to these arguments. Scientists will be empowered to participate in the public discussion and to engage the critics on these issues as they consider thoughtful, plausible responses to their concerns. Temporary moratoriums are recognized as a plausible approach to dealing with possible concerns of new scientific advancements.

Novel reverse-turn mimics inhibit farnesyl transferase.

Reverse-turn inducing bicyclic lactams were incorporated into the substrate sequence recognized by farnesyl transferase to create inhibitors of RAS farnesylation. While the free peptides did not show any effect on the farnesylation, their Fmoc-protected counterparts impede the transformation of RAS with IC50's in the low micromolar range.

Molecular forceps from combinatorial libraries prevent the farnesylation of Ras by binding to its carboxyl terminus.

INTRODUCTION: Ras is one of the major oncogenes. In order to function properly it has to undergo post-translational processing at its carboxyl terminus. It has been shown that inhibitors of farnesyl transferase, the first enzyme in the processing chain, can suppress the transforming activity of oncogenic Ras. RESULTS: We have identified molecular forceps, branched peptidic molecules, from combinatorial libraries that bind to the carboxyl terminus of Ras and interfere with its farnesylation without inhibiting the farnesyl transferase. The active molecules were selected by a screening against the carboxy-terminal octapeptide of Ras. CONCLUSIONS: The implications of our findings are twofold. First, we demonstrate that it is possible to prevent enzymatic transformations by blocking the enzyme's access to its substrate using a synthetic small molecule to mask the substrate. Second, we show that it is feasible to derive molecules from combinatorial libraries that bind a specific epitope on a protein by selecting these molecules with the isolated peptide epitope.