Closely related gull species show contrasting foraging strategies in an urban environment.

The expansion of urban landscapes has both negative and positive effects on wildlife. Understanding how different species respond to urbanization is key to assessing how urban landscapes influence regional wildlife behavior and ecosystem structure. Gulls are often described as strong urban adapters, but few studies have explored species-specific differences in habitat use. Here, we use GPS tracking in conjunction with stable isotope analysis (SIA) to quantify the habitat use and trophic ecology of great black-backed gulls (Larus marinus) and herring gulls (L. argentatus) in an urbanized area. Non-Metric Multidimensional Scaling (NMDS) of foraging locations revealed significant differences in the habitat use between species. Great black-backed gulls foraged primarily in marine habitats and herring gulls foraged primarily in specific urban habitats (e.g., landfills, dumpsters) and showed higher site fidelity in terms of the proportion of foraging sites revisited. Further, great black-backed gulls had significantly higher δ15N and δ13C than herring gulls, reflecting the use of marine, rather than urban, food sources. This study highlights the variability in urban habitat utilization among closely related species, assesses stable isotope signatures of urban diets in wild birds, and discusses ecological implications of the relative contribution of urban and marine foraging.

Insights into the life history and ecology of a large shortfin mako shark Isurus oxyrinchus captured in southern California.

In June 2013, a record-breaking female Isurus oxyrinchus (total length 373 cm, mass 600 kg) was captured by rod and reel off Huntington Beach, California, where it was subsequently donated to research and provided a rare opportunity to collect the first data for a female I. oxyrinchus of this size. Counts of vertebral band pairs estimate the shark to have been c. 22 years old, depending upon assumptions of band-pair deposition rates, and the distended uteri and spent ovaries indicated that this shark had recently given birth. The stomach contained a c. 4 year-old female California sea lion Zalophus californianus that confirmed the high trophic position of this large I. oxyrinchus, which was corroborated with the high levels of measured contaminants and tissue isotope analyses.

Similarity-based modeling applied to signal detection in pharmacovigilance.

One of the main objectives in pharmacovigilance is the detection of adverse drug events (ADEs) through mining of healthcare databases, such as electronic health records or administrative claims data. Although different approaches have been shown to be of great value, research is still focusing on the enhancement of signal detection to gain efficiency in further assessment and follow-up. We applied similarity-based modeling techniques, using 2D and 3D molecular structure, ADE, target, and ATC (anatomical therapeutic chemical) similarity measures, to the candidate associations selected previously in a medication-wide association study for four ADE outcomes. Our results showed an improvement in the precision when we ranked the subset of ADE candidates using similarity scorings. This method is simple, useful to strengthen or prioritize signals generated from healthcare databases, and facilitates ADE detection through the identification of the most similar drugs for which ADE information is available.

Medication-wide association studies.

Undiscovered side effects of drugs can have a profound effect on the health of the nation, and electronic health-care databases offer opportunities to speed up the discovery of these side effects. We applied a "medication-wide association study" approach that combined multivariate analysis with exploratory visualization to study four health outcomes of interest in an administrative claims database of 46 million patients and a clinical database of 11 million patients. The technique had good predictive value, but there was no threshold high enough to eliminate false-positive findings. The visualization not only highlighted the class effects that strengthened the review of specific products but also underscored the challenges in confounding. These findings suggest that observational databases are useful for identifying potential associations that warrant further consideration but are unlikely to provide definitive evidence of causal effects.

Novel data-mining methodologies for adverse drug event discovery and analysis.

An important goal of the health system is to identify new adverse drug events (ADEs) in the postapproval period. Datamining methods that can transform data into meaningful knowledge to inform patient safety have proven essential for this purpose. New opportunities have emerged to harness data sources that have not been used within the traditional framework. This article provides an overview of recent methodological innovations and data sources used to support ADE discovery and analysis.

Machine learning and data mining: strategies for hypothesis generation.

Strategies for generating knowledge in medicine have included observation of associations in clinical or research settings and more recently, development of pathophysiological models based on molecular biology. Although critically important, they limit hypothesis generation to an incremental pace. Machine learning and data mining are alternative approaches to identifying new vistas to pursue, as is already evident in the literature. In concert with these analytic strategies, novel approaches to data collection can enhance the hypothesis pipeline as well. In data farming, data are obtained in an 'organic' way, in the sense that it is entered by patients themselves and available for harvesting. In contrast, in evidence farming (EF), it is the provider who enters medical data about individual patients. EF differs from regular electronic medical record systems because frontline providers can use it to learn from their own past experience. In addition to the possibility of generating large databases with farming approaches, it is likely that we can further harness the power of large data sets collected using either farming or more standard techniques through implementation of data-mining and machine-learning strategies. Exploiting large databases to develop new hypotheses regarding neurobiological and genetic underpinnings of psychiatric illness is useful in itself, but also affords the opportunity to identify novel mechanisms to be targeted in drug discovery and development.

Post-fundoplication contrast studies: is there room for improvement?

OBJECTIVE: Since the mid-1990s, laparoscopic fundoplication for gastro-oesophageal reflux disease has become the surgical procedure of choice. Several surgical groups perform routine post-operative contrast studies to exclude any (asymptomatic) anatomical abnormality and to expedite discharge from hospital. The purpose of this study was to determine the accuracy and interobserver reliability for surgeons and radiologists in contrast study interpretation. METHODS: 11 surgeons and 13 radiologists (all blinded to outcome) retrospectively reviewed the contrast studies of 20 patients who had undergone a laparoscopic fundoplication. Each observer reported on fundal wrap position, leak or extravasation of contrast and contrast hold-up at the gastro-oesophageal junction (on a scale of 0-4). A κ coefficient was used to evaluate interobserver reliability. RESULTS: Surgeons were more accurate than radiologists in identifying normal studies (specificity = 91.6% vs 78.9%), whereas both groups had similar accuracy in identifying abnormal studies (sensitivity = 82.3% vs 85.2%). There was higher agreement amongst surgeons than amongst radiologists when determining wrap position (κ = 0.65 vs 0.54). Both groups had low agreement when classifying a wrap migration as partial or total (κ = 0.33 vs 0.06). Radiologists were more likely to interpret the position of the wrap as abnormal (relative risk = 1.25) while surgeons reported a greater degree of hold-up of contrast at the gastro-oesophageal junction (mean score = 1.17 vs 0.86). CONCLUSION: Radiologists would benefit from more information about the technical details of laparoscopic anti-reflux surgery. Standardised protocols for performing post-fundoplication contrast studies are needed.

Protein expression profiles in pediatric multiple sclerosis: potential biomarkers.

The diagnosis of pediatric multiple sclerosis (MS) is challenging due to its low frequency and the overlap with other acquired childhood demyelinating disorders of the central nervous system. To identify potential protein biomarkers which could facilitate the diagnosis, we used two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry to identify proteins associated with pediatric MS. Plasma samples from nine children with MS and nine healthy subjects, matched in aggregate by age and gender, were analyzed for differences in their patterns of protein expression. We found 12 proteins that were significantly up regulated in the pediatric MS group: alpha-1-acid-glycoprotein 1, alpha-1-B-glycoprotein, transthyretin, apoliprotein-C-III, serum amyloid P component, complement factor-I, clusterin, gelsolin, hemopexin, kininogen-1, hCG1993037-isoform, and vitamin D-binding protein. These results show that 2-DE in combination with mass spectrometry is a highly sensitive technique for the identification of blood-based biomarkers. This proteomic approach could lead to a new panel of diagnostic and prognostic markers in pediatric MS.

Analgesia for colposcopy: double-masked, randomized comparison of ibuprofen and benzocaine gel.

OBJECTIVE: To evaluate pain relief effectiveness of oral ibuprofen and topical benzocaine gel during colposcopy. METHODS: In a double-masked, randomized controlled trial, women who attended a family medicine colposcopy clinic received one of four treatments, 800 mg of oral ibuprofen, 20% topical benzocaine, both, or placebos. Using visual analog scales, women recorded their pain after speculum placement, endocervical curettage (ECC), and cervical biopsy. Participants were 18-55 years old, spoke English, and were not taking other pain or psychotropic medications. Demographic and historical information was collected from each participant. RESULTS: Ninety-nine subjects participated. Twenty-five received oral ibuprofen and topical benzocaine (median pain scores on a 10-point scale for speculum placement, ECC, and biopsy were 0.75, 3.00, and 3.38, respectively), 24 received oral placebo and topical benzocaine (1.00, 3.75, and 2.63), 24 received oral ibuprofen and topical placebo (0.63, 3.75, and 2.25), and 26 received oral and topical placebos (0.75, 3.50, and 3.00). There were no statistically significant differences in patient visual analogue pain scale scores across the four groups (statistical power, ECC = 0.74, cervical biopsy = 0.62). Younger women and women who had pain with speculum placement were more likely to have increased pain during ECC. Increased pain during biopsy was associated with history of severe dysmenorrhea but no other demographic or historical factors. Women overall reported ECC and biopsy to be mildly painful, with median scores of 3.5 for ECC and 2.75 for biopsy on a 10-point scale. The range in pain scores was large, with some women reporting severe pain (for ECC minimum = 0.25, maximum = 10.0; biopsy: minimum = 0.0, maximum = 9.0). CONCLUSION: Colposcopy is perceived as somewhat painful, but oral ibuprofen and topical benzocaine gel, alone or together, provided no advantage over placebo in decreasing colposcopy pain.

Differences in fertility patterns between urban and rural women in Washington State, 1983-1984 to 1993-1994.

We use data on Washington State abortions and births for 1983-1984 and 1993-1994 to analyze trends for urban and rural women, using the demographic measures total abortion and total fertility rates. These express pacing of childbearing in a single number which is simple to calculate and interpret, and is age-standardized. We find significant urban-rural differences. Total abortion rates decline and total fertility rates increase in both areas. However, the relative magnitudes of pacing decreases in abortions for rural women and increases in births for urban women are striking. The demographic measures are useful interpretive tools, and can be applied to a broad range of questions.

Reproductive health services in rural Washington State: scope of practice and provision of medical abortions, 1996-1997.

OBJECTIVES: This study explored reproductive health care in rural Washington State, reasons given by providers for not offering abortions, and providers' willingness to use medical abortifacients. METHODS: Physicians, midwives, nurse practitioners, and physician assistants in rural Washington completed an inventory of reproductive health services that they provide, whether and why they do not perform abortions, and whether they would use medical abortifacients. RESULTS: Of the respondents, 89.2% reported providing reproductive health care. Only 1.2% reported performing surgical abortions, and 26.1% indicated that they would probably prescribe medical abortifacients. CONCLUSIONS: Few providers offer surgical abortions in rural Washington. Greater numbers report a willingness to prescribe medical abortifacients.

A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma.

BACKGROUND: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) by reducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2-deoxyuridine-5-monophosphate (FdUMP), one of the principal active metabolites of 5-FU, the scheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of 1 mM for six or more hours, significantly enhances the efficacy of 5-FU. PATIENTS AND METHODS: 5-FU/FA was given as follows: days 1 and 2-FA 250 mg/m2 (max. 350 mg) over two hours followed by 5-FU 400 mg/m2 by intravenous bolus (i.v.b.) over 15 minutes and subsequently 5-FU 400 mg/m2 infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g i.v.b. over 15 minutes followed by 12 g ivi over 12 hours. RESULTS: Thirty patients were entered into the study. Median survival was nine months (range 1-51+ months). There were eight partial responses (28%, 95% CI: 13%-47%). The median duration of response was 6.5 (range 4-9 months). Grade 3-4 toxicities included neutropenia (grade 3 in eight patients and grade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment was complicated by pulmonary embolism in one patient and deep venous thrombosis in another. CONCLUSION: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.

Abortion services in rural Washington State, 1983-1984 to 1993-1994: availability and outcomes.

CONTEXT: Fewer rural health providers offer abortion services than a decade ago. It is unknown how the reduction in service availability has affected women's pregnancy outcomes, the extent to which they must travel to obtain an abortion or whether abortions are delayed as a result. METHODS: Population, birth and fetal death data, as well as pregnancy termination reports, obtained from Washington State were used to calculate abortion rates and ratios and birthrates for Washington residents in 1983-1984 and in 1993-1994. Residence of abortion patients was classified by county only, and location of providers was recorded as large urban county, small urban county, large rural county or small rural county. Distances that women traveled to obtain an abortion were calculated. Chi-square tests were used to compare urban and rural rates and ratios within time periods, and to compare changes that occurred between time periods. RESULTS: Birthrates and abortion rates decreased for both rural and urban Washington women between 1983-1984 and 1993-1994, but the magnitude of the decrease was greater for rural women. The rural abortion rate fell 27%, from 14.9 abortions per 1,000 women to 10.9 per 1,000, while the urban rate dropped 17%, from 21.8 to 18.2 per 1,000. The decline in the abortion rate was larger for adolescents than it was for other age-groups. In rural areas, the abortion rate decreased from 16.5 per 1,000 adolescents aged 10-19 in 1983-1984 to 10.8 per 1,000 in 1993-1994, while it declined from 23.3 per 1,000 to 16.9 per 1,000 in urban areas. From the earlier to the later time period, rural women traveled on average 12 miles farther each way to obtain an abortion, and the proportion who obtained the procedure in a rural county decreased from 25% to 3%. In the earlier time period, 62% of rural women traveled 50 miles or more to obtain an abortion, compared with 73% in 1993-1994. From 1983-1984 to 1993-1994, the proportion of rural women who traveled out of state for an abortion increased from 8% to 14%. The proportion of rural women terminating their pregnancy after the first trimester increased from 8% in 1983-1984 to 15% in 1993-1994. CONCLUSION: Rural Washington women are traveling farther and more often to urban and out-of-state locations for abortion services, and are obtaining their abortions at a later gestational age, which is associated with a decade-long decline in the number of abortion providers.

PIP: The availability and outcome of abortion services as of 1983-84 and 1993-94 in rural Washington State were investigated. The population data include birth, fetal death and pregnancy termination which came from the vital statistics data compiled by Washington State. Results showed that birth rates and abortion rates decreased throughout the state from 1983-84 to 1993-94. The magnitude of the drop in abortion rates was significantly greater in rural than in urban women (p 0.01). The rural abortion rate fell 27% compared with a 17% drop in the urban rate. The declination in the abortion rate was larger for adolescents than other age groups. The abortion rate for adolescents aged 10-19 years dropped 35% in rural areas and 28% in urban areas. 12 miles increased the distance that rural women traveled to obtain abortion. The proportion of rural women having abortions decreased significantly from 25% to 3%. During 1983-84, 62% traveled 50 miles to obtain abortion compared with 73% in 1993-94. In both time periods, the proportion of rural women who traveled out of state for an abortion increased from 8% to 14%. Furthermore, the proportion of women terminating their pregnancy after the first trimester increased from 8% in 1983-84 to 15% in 1993-94. More work is needed to understand the relationships among provider availability, other factors influencing decision-making and pregnancy outcomes.

Novel azacyclic ureas that are potent inhibitors of HIV-1 protease.

A series of novel, azacyclic ureas which are highly potent inhibitors of the HIV-1 protease (IC50 = 4.1 to < 0.5 nM) were synthesized. Aqueous solubilities of this series of compounds were improved by incorporating polar functional groups at the P1' P2 and P2' positions. These compounds also possess good anti-viral activity by inhibition of the cytopathic effect of HIV-13B in MT-4 cells in vitro.

A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease.

The design, synthesis, and molecular modeling studies of a novel series of azacyclic ureas, which are inhibitors of human immunodeficiency virus type 1 (HIV-1) protease that incorporate different ligands for the S1', S2, and S2' substrate-binding sites of HIV-1 protease are described. The synthesis of this series is highly flexible in the sense that the P1', P2, and P2' residues of the inhibitors can be changed independently. Molecular modeling studies on the phenyl ring of the P2 and P2' ligand suggested incorporation of hydrogen-bonding donor/acceptor groups at the 3' and 4-positions of the phenyl ring should increase binding potency. This led to the discovery of compound 7f (A-98881), which possesses high potency in the HIV-1 protease inhibition assay and the in vitro MT-4 cell culture assay (Ki = approximately 5 pM and EC50 = 0.002 microM). This compares well with the symmetrical cyclic urea 1 pioneered at DuPont Merck.

Determination of proanthocyanidins and catechins in beer and barley by high-performance liquid chromatography with dual-electrode electrochemical detection.

A method was developed to determine the flavanols prodelphinidin B3, procyanidin B3, (+)-catechin, and (-)-epicatechin by high-performance liquid chromatography, using dual-channel electrochemical detection. This method was especially suited to the direct analysis of beer samples and to analysis of acetone extracts of barley samples, and was capable of determining proanthocyanidins and catechins at levels of 0.1-5.0 mg l-1. The use of dual-channel electrochemical detection also enabled unambiguous peak identification by measurement of collection efficiencies. This method offered improved sensitivity and selectivity compared with ultraviolet detection, and sample preparation procedures were greatly simplified. The method was applied to the comparison of stabilized and unstabilized lagers, and to the analysis of different barley varieties grown in Ireland.

Ultrasonic imaging for extracorporeal shockwave lithotripsy: analysis of factors in successful treatment.

The emergence of real-time ultrasonic imaging for extracorporeal shockwave lithotripsy poses questions regarding the factors and techniques which facilitate stone imaging for clinicians with no previous practical experience in ultrasonography. The ability of these clinicians to assess when stone disintegration has been achieved also needs to be confirmed. A wide range of data was recorded from each of 2688 lithotripsy treatments performed over a 2-year period using the EDAP LT.01 ultrasound-imaged piezoelectric lithotriptor. An analysis of these data was performed using a comprehensive microcomputer-based statistics package. The mean time taken for stone imaging and positioning was reduced from 11.2 to 7.5 min over the 2-year period. Obese patients and those with renal pelvic stones were best imaged in a lateral position. Overall there was no difference in percentage stone disintegration or clearance between treatments in the supine or lateral positions, but a significant reduction in the clearance of small caliceal stones resulted when the lateral position was used. Factors associated with a significantly greater percentage of stone disintegration and clearance included pain experienced by the patient during fine adjustment of the processing head during treatment, acoustic focus attenuation and widening and acoustic shadow widening as detected by the urologist at the end of treatment. Among the factors not associated with significant alterations in the percentage of stone disintegration or clearance were the lithotriptor operator, the side or site of the calculus, obesity and shockwave frequency or power. This study confirmed the ability of urologists to develop expertise in ultrasonography for renal stone imaging and to interpret successfully the subtle signs of stone disintegration.