Use of multiple data sources to identify specific drugs and other factors associated with drug and alcohol screening of fatally injured motor vehicle drivers.

OBJECTIVE: Drugged driving crashes have significantly increased over the past two decades. The objectives of this study were to identify and characterize the drugs present in motor vehicle driver fatalities using multiple surveillance data sources; assess concordance of the data sources in identifying drug presence; and identify demographic and crash factors associated with drug and alcohol screening in fatally injured motor vehicle drivers. METHODS: Fatality Analysis Reporting System (FARS), Collision Report Analysis for Safer Highways (CRASH), and mortality data sets were linked; drug screening and positive drug screens were identified. Chi-square and conditional logistic regression were performed. RESULTS: The use of FARS data identified the majority of positive drug screens in the linked data set. Supplementation of FARS data with death certificate and CRASH data increased identification of specific drugs and drug classes detected among fatally injured motor vehicle drivers, although there was a low concordance among the data sources. Alcohol and depressants such as alprazolam had the highest frequencies among fatally injured drivers. Speeding, lack of occupant restraints, young age, commercial truck drivers, and speeding were all factors associated with increased odds of the fatally injured driver being drug or alcohol screened. CONCLUSIONS: These findings indicate that FARS drug information data may be strengthened through increased autopsy and consultation with medical examiners to better understand and interpret decedent toxicology testing results, and that states with low driver drug testing rates should consider mandatory driver drug testing in fatal crashes.

Surveillance of traffic incident management-related occupational fatalities in Kentucky, 2005-2016.

OBJECTIVE: Traffic incidents occurring on roadways require the coordinated effort of multiple responder and recovery entities, including communications, law enforcement, fire and rescue, emergency medical services, hazardous materials, transportation agencies, and towing and recovery. The objectives of this study were to (1) identify and characterize transportation incident management (TIM)-related occupational fatalities; (2) assess concordance of surveillance data sources in identifying TIM occupations, driver vs. pedestrian status, and occupational fatality incident location; and (3) determine and compare U.S. occupational fatality rates for TIM industries. METHODS: The Kentucky Fatality Assessment and Control Evaluation (FACE) program analyzed 2005-2016 TIM occupational fatality data using multiple data sources: death certificate data, Collision Report Analysis for Safer Highways (CRASH) data, and media reports, among others. Literal text analysis was performed on FACE data, and a multiple linear regression model and SAS proc sgpanel were used to estimate and visualize the U.S. TIM occupational mortality trend lines and confidence bounds. RESULTS: There were 29 TIM fatalities from 2005 to 2015 in Kentucky; 41% of decedents were in the police protection occupation, and 21% each were in the fire protection and motor vehicle towing industries. Over one half of the TIM decedents were performing work activities as pedestrians when they died. Media reports identified the majority of the occupational fatalities as TIM related (28 of 29 TIM-related deaths); the use of death certificates as the sole surveillance data source only identified 17 of the 29 deaths as TIM related, and the use of CRASH data only identified 4 of the 29 deaths as TIM related. Injury scenario text analysis showed that law enforcement vehicle pursuit, towing and recovery vehicle loading, and disabled vehicle response were particular high-risk activities that led to TIM deaths. Using U.S. data, the motor vehicle towing industry had a significantly higher risk for occupational mortality compared to the fire protection and police protection industries. CONCLUSIONS: Multiple data sources are needed to comprehensively identify TIM fatalities and to examine the circumstances surrounding TIM fatalities, because no one data source in itself was adequate and undercounted the total number of TIM fatalities. The motor vehicle towing industry, in particular, is at elevated risk for occupational mortality, and targeted mandatory TIM training for the motor vehicle towing industry should be considered. In addition, enhanced law enforcement roadside safety training during vehicle pursuit and apprehension of suspects is recommended.

Geostatistical analysis of tritium, groundwater age and other noble gas derived parameters in California.

Key characteristics of California groundwater systems related to aquifer vulnerability, sustainability, recharge locations and mechanisms, and anthropogenic impact on recharge are revealed in a spatial geostatistical analysis of a unique data set of tritium, noble gases and other isotopic analyses unprecedented in size at nearly 4000 samples. The correlation length of key groundwater residence time parameters varies between tens of kilometers ((3)H; age) to the order of a hundred kilometers ((4)Heter; (14)C; (3)Hetrit). The correlation length of parameters related to climate, topography and atmospheric processes is on the order of several hundred kilometers (recharge temperature; δ(18)O). Young groundwater ages that highlight regional recharge areas are located in the eastern San Joaquin Valley, in the southern Santa Clara Valley Basin, in the upper LA basin and along unlined canals carrying Colorado River water, showing that much of the recent recharge in central and southern California is dominated by river recharge and managed aquifer recharge. Modern groundwater is found in wells with the top open intervals below 60 m depth in the southeastern San Joaquin Valley, Santa Clara Valley and Los Angeles basin, as the result of intensive pumping and/or managed aquifer recharge operations.

Further evaluation and validation of a commercially available competitive ELISA (cELISA) for the detection of antibodies specific to equine arteritis virus (EAV).

The purpose of this study was to further evaluate and validate two commercially available equine arteritis virus (EAV) competitive ELISAs (original and enhanced cELISAs) using archived equine sera from experimentally inoculated animals and field sera submitted for laboratory diagnosis. First, the original and subsequently enhanced cELISAs were compared with the virus neutralisation test (VNT) using a panel of archived serum samples from experimentally inoculated animals. Then, the enhanced cELISA was compared with the VNT using a large panel of archived serum samples. The total number of equine sera tested was 3255, which included sera against 25 different EAV strains. The study confirmed that the enhanced cELISA was more sensitive than the original cELISA. Based on testing sera from experimentally inoculated animals and field sera, the enhanced cELISA had an estimated sensitivity (98.9 percent and 99.6 percent, respectively) and specificity (98.3 percent and 98.7 percent, respectively). The currently marketed enhanced VMRD EAV antibody cELISA test kit (VMRD Inc., Pullman, Washington, USA) has high sensitivity and specificity relative to the VNT. Based on the findings of this study, the authors would propose that the enhanced cELISA should be considered as an alternative approved method to the VNT for the detection of antibodies to EAV.

Descriptive analysis of longitudinal endoscopy for exercise-induced pulmonary haemorrhage in Thoroughbred racehorses training and racing at the Hong Kong Jockey Club.

REASONS FOR PERFORMING STUDY: Exercise-induced pulmonary haemorrhage (EIPH) is reported as a performance limiting condition in racehorses, yet few longitudinal studies characterising EIPH have been reported. OBJECTIVES: To characterise EIPH during training and racing in the absence of prophylactic medication with furosemide among horses imported to Hong Kong during 2007-2012. STUDY DESIGN: Retrospective descriptive study of clinical endoscopy, EIPH status, and racing records. METHODS: Thoroughbred geldings (n = 822) imported from New Zealand between 2007 and 2012 were retrospectively assigned to 4 groups: diagnosed with EIPH via endoscopy (EIPH+), graded using recognised criteria; observed with epistaxis (Epistaxis); free of EIPH on endoscopy (EIPH-); and those in which no endoscopy was performed. RESULTS: The majority of horses (89%) were subjected to endoscopy once or more (median 15, interquartile range 3-18). Of those undergoing endoscopy, 55% of horses were diagnosed EIPH+ which varied in severity. Few (4%) experienced epistaxis. EIPH+ was diagnosed most frequently (63%) after racing. There was no significant difference in the proportion of EIPH+ and EIPH- horses that raced. Racing career longevity was longest for EIPH+ horses. The number of starts in Hong Kong for EIPH+ horses was not significantly different to EIPH- horses. [Correction added on 9 January 2015, after first online publication: The term 'lifetime starts' has been changed to 'starts in Hong Kong' in the preceding sentence.] Days to retirement were longer for EIPH+ horses. Horses with mild EIPH+ (grade <3) were more likely to be retired for other causes whereas severe grades (≥3) were more likely to be retired for EIPH. CONCLUSIONS: Exercise-induced pulmonary haemorrhage is common and varies in severity between individuals and between episodes in the same individual. There is no difference in racing career longevity between EIPH+ and EIPH- horses trained and raced without furosemide. See also correspondences by PS Morley and KW Hinchcliff; AD Richards; and S. Preston and C. M. Riggs.

Building locally relevant ethics curricula for nursing education in Botswana.

AIM: The goal of this multi-institutional collaboration was to develop an innovative, locally relevant ethics curriculum for nurses in Botswana. BACKGROUND: Nurses in Botswana face ethical challenges that are compounded by lack of resources, pressures to handle tasks beyond training or professional levels, workplace stress and professional isolation. Capacity to teach nursing ethics in the classroom and in professional practice settings has been limited. METHODS: A pilot curriculum, including cases set in local contexts, was tested with nursing faculty in Botswana in 2012. RESULTS: Thirty-three per cent of the faculty members indicated they would be more comfortable teaching ethics. A substantial number of faculty members were more likely to introduce the International Council of Nurses Code of Ethics in teaching, practice and mentoring as a result of the training. Based on evaluation data, curricular materials were developed using the Code and the regulatory requirements for nursing practice in Botswana. A web-based repository of sample lectures, discussion cases and evaluation rubrics was created to support the use of the materials. DISCUSSION: A new master degree course, Nursing Ethics in Practice, has been proposed for fall 2015 at the University of Botswana. The modular nature of the materials and the availability of cases set within the context of clinical nurse practice in Botswana make them readily adaptable to various student academic levels and continuing professional development programmes. CONCLUSION: The ICN Code of Ethics for Nursing is a valuable teaching tool in developing countries when taught using locally relevant case materials and problem-based teaching methods. IMPLICATIONS FOR NURSING: The approach used in the development of a locally relevant nursing ethics curriculum in Botswana can serve as a model for nursing education and continuing professional development programmes in other sub-Saharan African countries to enhance use of the ICN Code of Ethics in nursing practice.

Identifying rare variants for genetic risk through a combined pedigree and phenotype approach: application to suicide and asthma.

Suicidal behavior is a complex disorder, with evidence for genetic risk independent of other genetic risk factors including psychiatric disorders. Since 1996, over 3000 DNA samples from Utah suicide decedents have been collected and banked for research use through the Utah Medical Examiner. In addition, over 12,000 Utah suicides were identified through examination of death certificates back to 1904. By linking this data with the Utah Population Database, we have identified multiple extended pedigrees with increased risk for suicide completion. A number of medical conditions co-occur with suicide, including asthma, and this study was undertaken to identify genetic risk common to asthma and suicide. This study tests the hypothesis that a particular comorbid condition may identify a more homogeneous genetic subgroup, facilitating the identification of specific genetic risk factors in that group. From pedigrees at increased risk for suicide, we identified three pedigrees also at significantly increased familial risk for asthma. Five suicide decedents from each of these pedigrees, plus an additional three decedents not from these pedigrees with diagnosed asthma, and 10 decedents with close relatives with asthma were genotyped. Results were compared with 183 publicly available unaffected control exomes from 1000 Genomes and CEPH (Centre d'etude du polymorphisme humain) samples genotyped on the same platform. A further 432 suicide decedents were also genotyped as non-asthma suicide controls. Genotyping was done using the Infinium HumanExome BeadChip. For analysis, we used the pedigree extension of Variant Annotation, Analysis and Search Tool (pVAAST) to calculate the disease burden of each gene. The Phenotype Driven Variant Ontological Re-ranking tool (Phevor) then re-ranked our pVAAST results in context of the phenotype. Using asthma as a seed phenotype, Phevor traversed biomedical ontologies and identified genes with similar biological properties to those known to result in asthma. Our top associated genes included those related to neurodevelopment or neural signaling (brain-derived neurotrophic factor (BDNF), neutral sphingomyelinase 2 (SMPD2), homeobox b2 (HOXB2), neural cell adhesion molecule (NCAM2), heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0)), inflammation (free fatty acid receptor 2 (FFAR2)) and inflammation with additional evidence of neuronal involvement (oxidized low density lipoprotein receptor 1 (OLR1), toll-like receptor 3 (TLR3)). Of particular interest, BDNF has been previously implicated in both psychiatric disorders and asthma. Our results demonstrate the utility of combining pedigree and co-occurring phenotypes to identify rare variants associated with suicide risk in conjunction with specific co-occurring conditions.

Concordance of motor vehicle crash, emergency department, and inpatient hospitalization data sets in the identification of drugs in injured drivers.

OBJECTIVE: Prescription drug overdoses, abuse, and sales have increased dramatically in the United States in the last decade. The purpose of the present study was to link crash data with emergency department (ED) and inpatient hospitalization data to assess the concordance between the data sets in the identification of the presence of drugs among injured motor vehicle drivers (passenger cars, passenger trucks, light trucks, and semi-trucks) in Kentucky. METHODS: Kentucky CRASH data were probabilistically linked to ED data sets for years 2008-2010 and to inpatient hospitalization data sets for years 2000-2010. Statistical analyses were performed. RESULTS: Of the 72,529 linked crash/ED visits, there were 473 drivers with an associated nondependent abuse of drugs diagnosis in the ED, and 930 drivers had drug involvement recorded in the CRASH data (only 163 cases overlapped with drug involvement both recorded in CRASH data and coded as nondependent abuse of drugs in the ED); 64 drivers had multiple drug types present in their system. Of the 20,860 total linked crash/inpatient hospitalization cases, there were 973 drivers diagnosed with nondependent abuse of drugs in the inpatient hospitalization record and 499 drivers had drug involvement recorded in the CRASH data (only 207 overlapped); 250 drivers were diagnosed with multiple drugs in their system. CONCLUSIONS: Surveillance data from multiple public health data sets is necessary to identify the presence of drugs in injured drivers involved in motor vehicle crashes. The use of a single surveillance data set alone may significantly underreport the number of drugged drivers who were injured in a motor vehicle collision.

The radioactive autopsy: safe working practices.

Autopsy cases involving individuals retaining radioactive substances are fortunately rare, but when they occur they can impose significant radiation safety and legal requirements. This review aims to improve the understanding of these issues so that appropriate precautions are implemented when necessary. This review describes the properties of ionizing radiations, natural and man-made sources of ionizing radiation and its use in healthcare. It identifies the most likely circumstances leading to radioactive substances being present during autopsy and sources of information, including radiation protection advice. It discusses precautions that may need to be implemented prior to, during and following autopsy. Despite the issue of appropriate information to patients and next of kin, it is inevitable that some cases will be identified only at autopsy and it is important that robust local procedures are maintained. Information must be communicated to assist safe management of the body and liaison between relevant professional groups may be needed to standardize methods of communication. Provided that appropriate precautions are implemented, determined through consultation with a qualified expert in radiation protection and by completion of risk assessment, the radioactive autopsy can be undertaken safely and in compliance with relevant legislative requirements.

Saturated zone denitrification: potential for natural attenuation of nitrate contamination in shallow groundwater under dairy operations.

We present results from field studies at two central California dairies that demonstrate the prevalence of saturated-zone denitrification in shallow groundwater with 3H/ 3He apparent ages of < 35 years. Concentrated animal feeding operations are suspected to be major contributors of nitrate to groundwater, but saturated zone denitrification could mitigate their impact to groundwater quality. Denitrification is identified and quantified using N and O stable isotope compositions of nitrate coupled with measurements of excess N2 and residual NO3(-) concentrations. Nitrate in dairy groundwater from this study has delta15N values (4.3-61 per thousand), and delta18O values (-4.5-24.5 per thousand) that plot with delta18O/delta15N slopes of 0.47-0.66, consistent with denitrification. Noble gas mass spectrometry is used to quantify recharge temperature and excess air content. Dissolved N2 is found at concentrations well above those expected for equilibrium with air or incorporation of excess air, consistent with reduction of nitrate to N2. Fractionation factors for nitrogen and oxygen isotopes in nitrate appear to be highly variable at a dairy site where denitrification is found in a laterally extensive anoxic zone 5 m below the water table, and at a second dairy site where denitrification occurs near the water table and is strongly influenced by localized lagoon seepage.

Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions.

OBJECTIVE: To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules. DESIGN: Phase I pharmacokinetics study. SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 +/- 8 years. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids. MEASUREMENTS AND RESULTS: Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC(0-infinity) of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5-fold and AUC(0-infinity) 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC(0-infinity) were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.

Crystallization and preliminary X-ray analysis of RecG, a replication-fork reversal helicase from Thermotoga maritima complexed with a three-way DNA junction.

The monomeric 3'-5' helicase RecG from the thermophilic bacterium Thermotoga maritima has been crystallized in complex with a three-way DNA junction, the preferred physiological substrate. The crystals were obtained by hanging-drop vapour diffusion. The crystals belong to space group C2, with unit-cell parameters a = 133.7, b = 144.6, c = 84.0 A, beta = 113.8 degrees. Native data to a resolution of 3.25 A were collected from crystals flash-cooled to 100 K.

Structural analysis of DNA replication fork reversal by RecG.

The stalling of DNA replication forks that occurs as a consequence of encountering DNA damage is a critical problem for cells. RecG protein is involved in the processing of stalled replication forks, and acts by reversing the fork past the damage to create a four-way junction that allows template switching and lesion bypass. We have determined the crystal structure of RecG bound to a DNA substrate that mimics a stalled replication fork. The structure not only reveals the elegant mechanism used by the protein to recognize junctions but has also trapped the protein in the initial stage of fork reversal. We propose a mechanism for how forks are processed by RecG to facilitate replication fork restart. In addition, this structure suggests that the mechanism and function of the two largest helicase superfamilies are distinct.

Cloning, expression, and characterization of pyrrolidone carboxyl peptidase from the archaeon Thermococcus litoralis.

The gene encoding pyrrolidone carboxyl peptidase (Pcp) has been cloned from the hyperthermophilic archaeon Thermococcus litoralis. The recombinant enzyme has been expressed in Escherichia coli, purified, and characterized. The T. litoralis Pcp demonstrates strong sequence homology to previously characterized bacterial Pcps. Some investigations have been carried out on enzyme substrate specificity and stability.

DNA ligases in the repair and replication of DNA.

DNA ligases are critical enzymes of DNA metabolism. The reaction they catalyse (the joining of nicked DNA) is required in DNA replication and in DNA repair pathways that require the re-synthesis of DNA. Most organisms express DNA ligases powered by ATP, but eubacteria appear to be unique in having ligases driven by NAD(+). Interestingly, despite protein sequence and biochemical differences between the two classes of ligase, the structure of the adenylation domain is remarkably similar. Higher organisms express a variety of different ligases, which appear to be targetted to specific functions. DNA ligase I is required for Okazaki fragment joining and some repair pathways; DNA ligase II appears to be a degradation product of ligase III; DNA ligase III has several isoforms, which are involved in repair and recombination and DNA ligase IV is necessary for V(D)J recombination and non-homologous end-joining. Sequence and structural analysis of DNA ligases has shown that these enzymes are built around a common catalytic core, which is likely to be similar in three-dimensional structure to that of T7-bacteriophage ligase. The differences between the various ligases are likely to be mediated by regions outside of this common core, the structures of which are not known. Therefore, the determination of these structures, along with the structures of ligases bound to substrate DNAs and partner proteins ought to be seen as a priority.

Crystal structure of T7 gene 4 ring helicase indicates a mechanism for sequential hydrolysis of nucleotides.

We have determined the crystal structure of an active, hexameric fragment of the gene 4 helicase from bacteriophage T7. The structure reveals how subunit contacts stabilize the hexamer. Deviation from expected six-fold symmetry of the hexamer indicates that the structure is of an intermediate on the catalytic pathway. The structural consequences of the asymmetry suggest a "binding change" mechanism to explain how cooperative binding and hydrolysis of nucleotides are coupled to conformational changes in the ring that most likely accompany duplex unwinding. The structure of a complex with a nonhydrolyzable ATP analog provides additional evidence for this hypothesis, with only four of the six possible nucleotide binding sites being occupied in this conformation of the hexamer. This model suggests a mechanism for DNA translocation.

The phylogenetic affinities of Otavipithecus namibiensis.

The middle Miocene hominoid Otavipithecus namibiensis is the first and most complete fossil ape from sub-equatorial Africa and represents a significant addition to the taxonomically sparse African middle Miocene hominoid fossil record. The Otavipithecus hypodigm comprises the holotype mandible, which presents a unique mosaic of dental and gnathic characters, and several attributed cranial and postcranial elements which resemble the stem hominoid Proconsul. Contrary to initial hopes that this discovery would provide new insights into hominoid morphological diversity and phylogenetic relationships, a variety of conflicting phylogenetic hypotheses have been advanced suggesting ties to virtually every major large-bodied hominoid group (Conroy et al., 1992; Andrews, 1992 a; Conroy, 1994; Pickford et al., 1994; Begun, 1994 a). Cladistic analysis of a matrix of 22 qualitative and ten quantitative characters of the mandible and mandibular dentition found no support for a close phylogenetic relationship between Otavipithecus and either the African ape or great ape clades, or with any of the Eurasian fossil hominoids with which it has previously been compared. A close relationship between Otavipithecus and Kenyapithecus cannot be ruled out, but is deemed unlikely on the basis both of morphological comparisons and the absence of support within a cladistic framework. The present analysis indicates that Otavipithecus is most closely related to Afropithecus, as previously suggested by Andrews (1992 a) among others. Due to lack of statistical support for this result, a conservative interpretation, that these taxa represented related but divergent lineages of a late early Miocene hominoid radiation, is currently favored. Findings are consistent with the allocation of Otavipithecus to Andrews' (1992 a) tribe Afropithecini which represents the sister group to Kenyapithecus and the extant ape clade.