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TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.

Background: Long QT syndrome (LQTS) is a potentially lethal, highly treatable cardiac channelopathy for which genetic testing has matured from discovery to translation and now clinical implementation.Objectives: Here we examine the spectrum and prevalence of mutations found in the first 2,500 unrelated cases referred for the FAMILION LQTS clinical genetic test.Methods: Retrospective analysis of the first 2,500 cases (1,515 female patients, average age at testing 23 +/- 17 years, range 0 to 90 years) scanned for mutations in 5 of the LQTS-susceptibility genes: KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6).Results: Overall, 903 referral cases (36%) hosted a possible LQTS-causing mutation that was absent in >2,600 reference alleles; 821 (91%) of the mutation-positive cases had single genotypes, whereas the remaining 82 patients (9%) had >1 mutation in > or =1 gene, including 52 cases that were compound heterozygous with mutations in >1 gene. Of the 562 distinct mutations, 394 (70%) were missense, 428 (76%) were seen once, and 336 (60%) are novel, including 92 of 199 in KCNQ1, 159 of 226 in KCNH2, and 70 of 110 in SCN5A.Conclusion: This cohort increases the publicly available compendium of putative LQTS-associated mutations by >50%, and approximately one-third of the most recently detected mutations continue to be novel. Although control population data suggest that the great majority of these mutations are pathogenic, expert interpretation of genetic test results will remain critical for effective clinical use of LQTS genetic test results. [ABSTRACT FROM AUTHOR]

PURPOSE: To compare a group exercise programme known as the Back to Fitness programme with individual physiotherapy for patients with non-specific low back pain from a materially deprived area. METHOD: This was a randomized controlled trial including 237 physiotherapy patients with back pain lasting more than six weeks. Participants were allocated to either the Back to Fitness programme or to individual physiotherapy, and followed up at three months and 12 months after randomization. The main outcome measure was the Roland Disability Questionnaire. Secondary measures were: SF12, EQ5D, Pain Self-Efficacy Scale. Health care diaries recording patients' use of health care resources were also collected over a 12-month period. RESULTS: There were no statistically significant differences in change scores between groups on the primary outcome measure at three months (CI - 2.24 to 0.49) and at 12 months (CI - 1.68 to 1.39). Only minor improvements in disability scores were observed in the Back to Fitness group at three months and 12 months respectively (mean change scores; - 0.89, - 0.77) and in the individual physiotherapy arm (mean change scores; - 0.02, - 0.63). Further analysis showed that patients from the most severely deprived areas were marginally worse at three month follow-up whereas those from more affluent areas tended to improve (CI 0.43 to 3.15). [ABSTRACT FROM AUTHOR]

Risk factors for college male sexual aggression that were both theoretically and empirically based were tested using multivariate regression analyses. These included substance abuse patterns, pornography consumption, negative gender-based attitudes, and child sexual abuse experiences. Regression analyses indicated that some gender attitudes, pornography use, and alcohol abuse were significant predictors of perpetration of sexual violence. Although a number of men were sexually abused as children, this risk factor did not predict sexual aggression as an adult. Many men reported alcohol-related sexual coercion and held many rape-supportive attitudes and beliefs. These practices by college men contribute to the prorape cultures found on many campuses. Strategies are needed to identify and intervene with high-risk men to prevent sexual victimization of women in college. [ABSTRACT FROM AUTHOR]

Given the recent focus on powered haulage incidents within the US mining sector, an appraisal of collision avoidance/warning systems (CXSs) through the lens of the available research literature is timely. This paper describes a rapid review that identifies, characterizes, and classifies the research literature to evaluate the maturity of CXS technology through the application of a Technology Readiness Assessment. Systematic search methods were applied to three electronic databases, and relevant articles were identified through the application of inclusion and exclusion criteria. Sixty-four articles from 2000 to 2020 met these criteria and were categorized into seven CXS technology categories. Review and assessment of the articles indicates that much of the literature-based evidence for CXS technology lies within lower levels of maturity (i.e., components and prototypes tested under laboratory conditions and in relevant environments). However, less evidence exists for CXS technology at higher levels of maturity (i.e., complete systems evaluated within operational environments) despite the existence of commercial products in the marketplace. This lack of evidence at higher maturity levels within the scientific literature highlights the need for systematic peer-reviewed research to evaluate the performance of CXS technologies and demonstrate the efficacy of prototypes or commercial products, which could be fostered by more collaboration between academia, research institutions, manufacturers, and mining companies. Additionally, results of the review reveal that most of the literature relevant to CXS technologies is focused on vehicle-to-vehicle interactions. However, this contrasts with haul truck fatal accident statistics that indicate that most haul truck fatal accidents are due to vehicle-to-environment interactions (e.g., traveling through a berm). Lastly, the relatively small amount of literature and segmented nature of the included studies suggests that there is a need for incremental progress or more stepwise research that would facilitate the improvement of CXS technologies over time. This progression over time could be achieved through continued long-term interest and support for CXS technology research., Competing Interests: Conflict of Interest The authors declare no competing interests.

Fragile X syndrome is rare but a prominent cause of intellectual disability. It is usually caused by a de novo mutation that occurs on multiple haplotypes and thus would not be expected to be detectible using genome-wide association (GWA). We conducted GWA in 89 male FXS cases and 266 male controls, and detected multiple genome-wide significant signals near FMR1 (odds ratio = 8.10, P = 2.5 × 10 -10 ). These findings withstood robust attempts at falsification. Fine-mapping yielded a minimum P = 1.13 × 10 -14 , but did not narrow the interval. Comprehensive functional genomic integration did not provide a mechanistic hypothesis. Controls carrying a risk haplotype had significantly longer FMR1 CGG repeats than controls with the protective haplotype (P = 4.75 × 10 -5 ), which may predispose toward increases in CGG number to the premutation range over many generations. This is a salutary reminder of the complexity of even "simple" monogenetic disorders.

Magnetic proximity detection systems (PDSs) used in underground mines occasionally generate false alarms when the miner-wearable component (MWC) is close to nearby conductors such as power cables. This is because the signals from the generators (antennas) of the PDS wirelessly couple to nearby cables, travel along these cables, and then couple back from the cable to a distant MWC to cause a false alarm. In order to manage such a false alarm, it is necessary to understand the basic near-field coupling characteristics from a generator to a long wire. Researchers from the National Institute for Occupational Safety and Health (NIOSH) have developed a method to measure such coupling characteristics for a ferrite-cored antenna to a straight wire. The method is introduced in this paper along with the test results.

TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O 3 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), formaldehyde (H 2 CO), glyoxal (C 2 H 2 O 2 ), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O 3 chemistry cycle. Multi-spectral observations provide sensitivity to O 3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.

Fine particulate matter (PM2.5) air pollution, varying in concentration and composition, has been shown to cause or exacerbate adverse effects on both human and ecological health. The concept of biomonitoring using deciduous tree leaves as a proxy for intraurban PM air pollution in different areas has previously been explored using a variety of study designs (e.g., systematic coverage of an area, source-specific focus), deciduous tree species, sampling strategies (e.g., single day, multi-season), and analytical methods (e.g., chemical, magnetic) across multiple geographies and climates. Biomonitoring is a low-cost sampling method and may potentially fill an important gap in current air monitoring methods by providing low-cost, longer-term urban air pollution measures. As such, better understanding of the range of methods, and their corresponding strengths and limitations, is critical for employing the use of tree leaves as biomonitors for pollution to improve spatially resolved exposure assessments for epidemiological studies and urban planning strategies.

Background: Childhood asthma morbidity has been associated with short-term air pollution exposure. To date, most investigations have used time-series models, and it is not well understood how exposure misclassification arising from unmeasured spatial variation may impact epidemiological effect estimates. Here, we develop case-crossover models integrating temporal and spatial individual-level exposure information, toward reducing exposure misclassification in estimating associations between air pollution and child asthma exacerbations in New York City (NYC)., Methods: Air pollution data included: (a) highly spatially-resolved intra-urban concentration surfaces for ozone and co-pollutants (nitrogen dioxide and fine particulate matter) from the New York City Community Air Survey (NYCCAS), and (b) daily regulatory monitoring data. Case data included citywide hospital records for years 2005-2011 warm-season (June-August) asthma hospitalizations (n=2353) and Emergency Department (ED) visits (n=11,719) among children aged 5-17 years. Case residential locations were geocoded using a multi-step process to maximize positional accuracy and precision in near-residence exposure estimates. We used conditional logistic regression to model associations between ozone and child asthma exacerbations for lag days 0-6, adjusting for co-pollutant and temperature exposures. To evaluate the effect of increased exposure specificity through spatial air pollution information, we sequentially incorporated spatial variation into daily exposure estimates for ozone, temperature, and co-pollutants., Results: Percent excess risk per 10ppb ozone exposure in spatio-temporal models were significant on lag days 1 through 5, ranging from 6.5 (95% CI: 0.2-13.1) to 13.0 (6.0-20.6) for inpatient hospitalizations, and from 2.9 (95% CI: 0.1-5.7) to 9.4 (6.3-12.7) for ED visits, with strongest associations consistently observed on lag day 2. Spatio-temporal excess risk estimates were consistently but not statistically significantly higher than temporal-only estimates on lag days 0-3., Conclusion: Incorporating case-level spatial exposure variation produced small, non-significant increases in excess risk estimates. Our modeling approach enables a refined understanding of potential measurement error in temporal-only versus spatio-temporal air pollution exposure assessments. As ozone generally varies over much larger spatial scales than that observed within NYC, further work is necessary to evaluate potential reductions in exposure misclassification for populations spanning wider geographic areas, and for other pollutants., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The continuous mining machine is a key piece of equipment used in underground coal mining operations. Over the past several decades these machines have been involved in a number of mine worker fatalities. Proximity detection systems have been developed to avert hazards associated with operating continuous mining machines. Incorporating intelligent design into proximity detection systems allows workers greater freedom to position themselves to see visual cues or avoid other hazards such as haulage equipment or unsupported roof or ribs. However, intelligent systems must be as safe as conventional proximity detection systems. An evaluation of the 39 fatal accidents for which the Mine Safety and Health Administration has published fatality investigation reports was conducted to determine whether the accident may have been prevented by conventional or intelligent proximity. Multiple zone configurations for the intelligent systems were studied to determine how system performance might be affected by the zone configuration. Researchers found that 32 of the 39 fatalities, or 82 percent, may have been prevented by both conventional and intelligent proximity systems. These results indicate that, by properly configuring the zones of an intelligent proximity detection system, equivalent protection to a conventional system is possible.

Background: Childhood asthma morbidity has been associated with ambient ozone in case-crossover studies. Varying effects of ozone by child age and sex, however, have been less explored., Methods: This study evaluates associations between ozone exposure and asthma emergency department visits and hospitalizations among boys and girls aged 5-17 years in New York City for the 2005-2011 warm season period. Time-stratified case-crossover analysis was conducted and, for comparison, time-series analysis controlling for season, day-of-week, same-day and delayed effects of temperature and relative humidity were also performed., Results: We found associations between ambient ozone levels and childhood asthma emergency department visits and hospitalizations in New York City, although the relationships varied among boys and girls and by age group. For an increase of interquartile range (0.013 ppm) in ozone, there was a 2.9-8.4% increased risk for boys and 5.4-6.5% for girls in asthma emergency department visits; and 8.2% increased risk for girls in hospitalizations. Among girls, we observed stronger associations among older children (10-13 and 14-17 year age groups). We did not observe significant modification by age for boys. Boys exhibited a more prompt response (lag day 1) to ozone than did girls (lag day 3), but significant associations for girls were retained longer, through lag day 6., Conclusions: Our study indicates significant variance in associations between short-term ozone concentrations and asthma events by child sex and age. Differences in ozone response for boys and girls, before and after puberty, may point towards both social (gendered) and biological (sex-linked) sources of effect modification.

Building on a unique exposure assessment project in New York, New York, we examined the relationship of particulate matter with aerodynamic diameter less than 2.5 μm and nitrogen dioxide with birth weight, restricting the population to term births to nonsmokers, along with other restrictions, to isolate the potential impact of air pollution on growth. We included 252,967 births in 2008-2010 identified in vital records, and we assigned exposure at the residential location by using validated models that accounted for spatial and temporal factors. Estimates of association were adjusted for individual and contextual sociodemographic characteristics and season, using linear mixed models to quantify the predicted change in birth weight in grams related to increasing pollution levels. Adjusted estimates for particulate matter with aerodynamic diameter less than 2.5 μm indicated that for each 10-µg/m(3) increase in exposure, birth weights declined by 18.4, 10.5, 29.7, and 48.4 g for exposures in the first, second, and third trimesters and for the total pregnancy, respectively. Adjusted estimates for nitrogen dioxide indicated that for each 10-ppb increase in exposure, birth weights declined by 14.2, 15.9, 18.0, and 18.0 g for exposures in the first, second, and third trimesters and for the total pregnancy, respectively. These results strongly support the association of urban air pollution exposure with reduced fetal growth.

A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0-5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) [alkenyl-B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2':SN2, and 99:1 enantiomeric ratio (er). NHC-Cu-catalyzed EAS with alkenyl-B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

We examined differentiation within the Colombian wood turtle Rhinoclemmys melanosterna, and among R. melanosterna and the closely allied species R. diademata, R.funerea and R. punctularia, based on 1060 base pairs of the mitochondrial cyt b gene. We also assessed the phylogenetic relationships among these species using 2050 bp of mtDNA (partial cyt b, 12S and 16S genes) and 3620 bp of nuclear DNA (partial Rag 1, Rag 2, C-mos, R35 and ODC genes). There is considerable phylogeographic structuring within R. melanosterna, with seven distinct clades distributed across the species' range. These clades correlate to some extent with previously described differences in the dorsal pattern of head coloration. Individual and combined analyses of mitochondrial and nuclear DNA indicated contradictory relationships among R. melanosterna, R. diademata, R. funerea and R. punctularia. Mitochondrial DNA sequences revealed R. melanosterna to be non-monophyletic with respect to R. diademata, R. funerea and R. punctularia. In contrast, R. melanosterna constituted a well-supported monophyletic clade using nuclear DNA. This conflict between mitochondrial and nuclear data suggests past gene flow among the allopatrically and parapatrically distributed species R. melanosterna, R. diademata, R. funerea and R. punctularia. Compared to the other Rhinoclemmys species, the taxa under study are weakly differentiated. To assess their taxonomic status, further research is warranted using additional nuclear markers and additional samples of R. diademata, R. funerea and R. punctularia. For the time being, a continued classification of R. melanosterna, R. diademata, R. funerea and R. punctularia as distinct species is justified owing to their allopatric and parapatric distributions, and to conserve the established usage of names that is based on morphological and karyotypic differentiation.

Aspercyclide A (1) is a biaryl ether containing 11-membered macrocyclic natural product antagonist of the human IgE-FcεRI protein-protein interaction (PPI); a key interaction in the signal transduction pathway for allergic disorders such as asthma. Herein we report a novel approach to the synthesis of the C19 methyl ether of aspercyclide A, employing a Pd(0)-catalysed, fluorous-tagged alkenylgermane/arylbromide macrocyclisation (germyl-Stille reaction) as the key step, and evaluation of both enantiomers of this compound via ELISA following optical resolution by CSP-HPLC. A crystal structure for germyl hydride 27 is also reported.

Background: The adverse respiratory effects of ground-level ozone are well established. Ozone is the air pollutant most consistently projected to increase under future climate change., Purpose: To project future pediatric asthma emergency department visits associated with ground-level ozone changes, comparing 1990s to 2020s., Methods: This study assessed future numbers of asthma emergency department visits for children aged 0-17 years using (1) baseline New York City metropolitan area emergency department rates; (2) a dose-response relationship between ozone levels and pediatric asthma emergency department visits; and (3) projected daily 8-hour maximum ozone concentrations for the 2020s as simulated by a global-to-regional climate change and atmospheric chemistry model. Sensitivity analyses included population projections and ozone precursor changes. This analysis occurred in 2010., Results: In this model, climate change could cause an increase in regional summer ozone-related asthma emergency department visits for children aged 0-17 years of 7.3% across the New York City metropolitan region by the 2020s. This effect diminished with inclusion of ozone precursor changes. When population growth is included, the projections of morbidity related to ozone are even larger., Conclusions: The results of this analysis demonstrate that the use of regional climate and atmospheric chemistry models make possible the projection of local climate change health effects for specific age groups and specific disease outcomes, such as emergency department visits for asthma. Efforts should be made to improve on this type of modeling to inform local and wider-scale climate change mitigation and adaptation policy., (Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Prenatal alcohol exposure can have detrimental effects on a child's development of adaptive behaviors necessary for success in the areas of academic achievement, socialization, and self-care. Sensory processing abilities have been found to affect a child's ability to successfully perform adaptive behaviors. The current study explored whether significant differences in sensory processing abilities, adaptive behavior, and neurocognitive functioning are observed between children diagnosed with partial Fetal Alcohol Syndrome (pFAS), Alcohol-Related Neurodevelopmental Disorder (ARND), or children who were prenatally exposed to alcohol (PEA), but did not meet criteria for an FASD diagnosis. The influence of IQ on adaptive behavior as well as further exploration of the relationship between sensory processing and adaptive behavior deficits among these children was also examined., Methods: A secondary analysis was conducted on some of the Short Sensory Profile (SSP) scores, Adaptive Behavior Assessment System--Second Edition (ABAS-II) scores, and Wechsler Intelligence Scale--Fourth Edition/Wechsler Preschool and Primary Scale of Intelligence--Third Edition (WISC- IV/WPPSI-III) scores of 46 children between 3 and 14 years of age with pFAS, ARND, or who were PEA., Results: Greater sensory processing deficits were found in children with a diagnosis of pFAS and ARND compared to those in the PEA group. Children with an ARND diagnosis scored significantly worse on measures of adaptive behavior than the PEA group. Children with pFAS scored significantly lower than children with ARND or PEA on perceptual/performance IQ. No correlation was found between IQ scores and adaptive behaviors across the FASD diagnostic categories. A significant positive correlation was found between SSP and ABAS-II scores., Conclusions: Regardless of the diagnosis received under the FASD umbrella, functional difficulties that could not be observed using traditional measures of intelligence were found, supporting guidelines that a broad range of standardized assessments be included when screening children for FASD.

The total syntheses of (+/-)-aspercyclide A (1) and its C19 methyl ether (15a) featuring Heck-Mizoroki macrocyclisation to form the 11-membered (E)-styrenyl biaryl ether lactone core are described.

The synthesis of a range of caged TRPV1 agonists and antagonists is reported. The photolysis characteristics of these compounds, when irradiated with a 355 nm laser, have been studied and in all cases the desired compound was produced. Photolysis of a caged TRPV1 agonist in cultured trigeminal neurons produced responses that were consistent with the activation of TRPV1 receptors.

Background: In the context of finite health resources, encouraging self-management of chronic conditions is important. Indeed, it is a key priority in the UK. An increasing number of self-management programmes are becoming available. However, patients may not always choose to participate in them. Some will prefer a more directed or medically orientated treatment. The acceptability of self-management programmes for patients suffering from chronic pain is an important issue. Few measures exist that examine the process of change to a self-management approach. The Pain Stages of Change Questionnaire (PSOCQ) was evaluated for this purpose in the present study. Hypotheses were centred around criterion and construct validity of the PSOCQ., Methods: A sample of pain patients was surveyed about their interest in participating in a lay-led self-management programme ('the Expert Patients Programme'). In addition, participants completed two psychometric measures: the Pain Stages of Change Questionnaire (PSOCQ) together with the Chronic Pain Acceptance Questionnaire (CPAQ). This is the first study as far as we are aware to examine these two scales together. The psychometric properties of the PSOCQ were examined. Analyses focused on the associations between the PSOCQ scores and interest in participating in the self-management programme. Further associations were examined between the PSOCQ and the Chronic Pain Acceptance Questionnaire., Results: The results demonstrated qualified support for the PSOCQ, in particular the Contemplation sub-scale. There was a significant positive association between interest and likelihood of joining the self-management programme and contemplation scores. The action and maintenance sub-scales appeared to be measuring a unitary dimension. The associations between the PSOCQ and the Chronic Pain Acceptance Questionnaire were in the directions predicted. The limitations of the study were discussed., Conclusion: The results showed some support for the PSOCQ as a potentially useful tool in assessing who may or may not be likely to join a self-management course.

Background: Genetic testing for congenital long QT syndrome (LQTS) has been performed in research laboratories for the past decade. Approximately 75% of patients with high clinical probability for LQTS have a mutation in one of five LQTS-causing cardiac channel genes. Possible explanations for the remaining genotype-negative cases include LQTS mimickers, novel LQTS-causing genes, unexplored regions of the known genes, and genetic testing detection failures., Objectives: The purpose of this study was to explore the possibility of allelic dropout as a possible mechanism underlying false-negative test results., Methods: The published primers currently used by many research laboratories to conduct a comprehensive analysis of the 60 translated exons in the KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6) genes were analyzed for the presence of common intronic single nucleotide polymorphisms (SNPs). Repeat mutational analysis, following primer/amplicon redesign using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, was performed on a cohort of 541 consecutive, unrelated patients referred for LQTS genetic testing., Results: Common (>1% minor allele frequency) intronic SNPs were discovered within the primer sequences of five of 60 translated exons. Following primer redesign to eliminate the possibility of allelic dropout, four previously genotype-negative index cases were found to possess LQTS-causing mutations: R591H-KCNQ1 and R594Q-KCNQ1 for exon 15 and E229X-KCNH2 in two unrelated cases. Repeat examination of these two amplicons in 400 reference alleles did not identify these or any additional amino acid variants., Conclusion: Allelic dropout secondary to intronic SNP-primer mismatch prevented the discovery of LQTS-causing mutations in four cases. Considering that many LQTS genetic testing research laboratories have used these primers, patients who reportedly are genotype negative may benefit from re-examination of those regions susceptible to allelic dropout due to primer-disrupting SNPs, particularly exon 15 in KCNQ1 and exon 4 in KCNH2.

Background: Satraplatin is thought to require reduction to a reactive Pt(II) complex (JM118) before exerting chemotherapeutic activity. In this study, we investigated the role of heme proteins in this reductive activation of satraplatin., Methods: Satraplatin was incubated in solution with heme proteins and liver microsomes. The oxidation state of heme iron was monitored by visible absorption spectrometry. Satraplatin and JM118 were detected using a sensitive and specific HPLC-ICPMS assay., Results: Satraplatin was stable in solutions containing haemoglobin, cytochrome c, glutathione, liver microsomes or NADH alone. However, in solutions containing haemoglobin plus NADH, satraplatin disappeared with a half-life of 35.8 mins. Under these conditions, satraplatin was reduced to JM118 and haemoglobin was oxidised to methaemoglobin. The reaction between haemoglobin and satraplatin was inhibited by carbon monoxide or by cooling the reaction solution. Cytochrome c and liver microsomes also reduced satraplatin to JM118 in a manner that depended upon the presence of NADH and was inhibited by carbon monoxide., Conclusion: This study has identified a mechanism of satraplatin activation involving metal-containing redox proteins and the transfer of electrons to the Pt(IV) drug from protein-complexed metal ions. Heme proteins may act by this mechanism as reducing agents for the activation of satraplatin in vivo.

Intracellular photolysis of a novel 'caged' capsaicin analogue results in in vitro activation of the capsaicin receptor TRPV1.

Chronic low back pain is the commonest cause of disability for adults of working age. It is a complex problem frequently encapsulated as a bio-psychosocial issue, yet the social element has received less attention than it deserves, particularly for low-income and socially deprived patients. Rehabilitation programmes are often based on increasing function through cognitive and behavioural techniques, which, for many reasons, may be less effective for the socially disadvantaged. In this paper we discuss the potential barriers to successful rehabilitation in socially deprived groups and we look at possible factors that may need to be considered when designing interventions.

International students underuse counseling services, which are grounded in Western cultural values. The authors describe a support group for Asian international students that they launched at a large midwestern university to help students feel at ease with American university life, address homesickness, language problems, and academic and social stressors. Co-leaders created a safe and culturally sensitive atmosphere where the women could network, socialize, and address their issues. Group treatment offers many advantages over individual counseling and can enhance the health of international students.

This article describes an innovative two-stage model of sexual assault therapy groups for women in a university setting. This model is recommended for use in various settings and includes a supportive therapy group and two specialized therapy groups, one for childhood sexual abuse survivors and the other for sexual assault (acquaintance rape and stranger rape) survivors. Theoretical underpinnings of the model are discussed in addition to practical aspects of group development such as elements of an effective group, screening of potential members, and marketing and recruitment techniques.

Previous work describing the embryonic stages of turtle development has not included members of the highly derived trionychid turtles. Staging criteria are described for the spiny softshell turtle (Apalone spinifera) to facilitate comparisons between phylogenetically distant taxa of turtles. Embryonic development in A. spinifera is placed in the context of the widely used sequence of Yntema stages. Novel features are included in the descriptions of staging criteria for Stages 13-26. Comparisons of the development of specific features are made between A. spinifera and other taxa of turtles. Data on the duration of developmental stages at different temperatures and embryo dimensions support the conclusion that morphology-based staging criteria are superior to developmental rate temperature coefficients., (Copyright 2002 Wiley-Liss, Inc.)

Purpose: Satraplatin is an orally administered platinum complex that has demonstrated clinical activity and manageable toxicity in phase II trials. The presence of several different platinum-containing species and very little intact parent drug in the systemic circulation indicates extensive biotransformation of satraplatin in vivo. To investigate the basis for the biotransformation of satraplatin, studies were carried out into the stability of the drug in whole blood and various other biological fluids in vitro., Methods: Concentrations of satraplatin and platinum-containing biotransformation products in incubation fluids were measured using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). The fate of satraplatin-derived platinum in whole blood in vitro was determined by analysis of blood fractions for platinum by ICPMS., Results: In fresh human whole blood in vitro, satraplatin concentrations fell very rapidly, resulting in a half-life for the disappearance of the drug of only 6.3 min (95% CI, 5.9 to 6.7 min). After the addition of drug to red blood cells that had been prepared from whole blood and suspended in 0.9% NaCl, satraplatin also disappeared very rapidly. Satraplatin was much more stable in fresh human plasma (t(1/2) 5.3 h) and fully supplemented cell culture medium (t(1/2) 22 h). Two new platinum-containing species appeared on HPLC-ICPMS platinum chromatograms of methanol extracts of plasma after the addition of the drug to whole blood. Their identities were assigned as the platinum(II) complex known as JM118 and a platinated protein with similar electrophoretic mobility to that of serum albumin. During the incubation of satraplatin in blood, platinum associated with red blood cells at an accumulation half-life of 9.5 min (95% CI, 7.1 to 14.2 min). At equilibrium, 62% of the added platinum was associated with red blood cells in a form that was not exchangeable in methanol or 0.9% NaCl., Conclusions: The rapid disappearance of satraplatin from human blood in vitro depends upon the presence of red blood cells. Generation of JM118 and irreversibly bound membrane- and protein-associated platinum indicates that satraplatin undergoes rapid biotransformation in whole blood.

The sea lamprey Petromyzon marinus is among the most primitive of extant vertebrates. We are interested in the organization of its Hox gene clusters, because, as a close relative of the gnathostomes, this information would help to infer Hox cluster organization at the base of the gnathostome radiation. We have partially mapped the P. marinus Hox clusters using phage, cosmid, and P1 artificial chromosome libraries. Complete homeobox sequences were obtained for the 22 Hox genes recovered in the genomic library screens and analyzed for cognate group identity. We estimate that the clusters are somewhat larger than those of mammals (roughly 140 kbp vs. 105 kbp) but much smaller than the single Hox cluster of the cephalochordate amphioxus (at more than 260 kb). We never obtained more than three genes from any single cognate group from the genomic library screens, although it is unlikely that our screen was exhaustive, and therefore conclude that P. marinus has a total of either three or four Hox clusters. We also identify four highly conserved non-coding sequence motifs shared with higher vertebrates in a genomic comparison of Hox 10 genes., (Copyright 2002 Wiley-Liss, Inc.)

Variation within genes has important implications for all biological traits. We identified 3899 single nucleotide polymorphisms (SNPs) that were present within 313 genes from 82 unrelated individuals of diverse ancestry, and we organized the SNPs into 4304 different haplotypes. Each gene had several variable SNPs and haplotypes that were present in all populations, as well as a number that were population-specific. Pairs of SNPs exhibited variability in the degree of linkage disequilibrium that was a function of their location within a gene, distance from each other, population distribution, and population frequency. Haplotypes generally had more information content (heterozygosity) than did individual SNPs. Our analysis of the pattern of variation strongly supports the recent expansion of the human population.

It is hypothesized on the basis of sex determination theory that species exhibiting genetic sex determination (GSD) may undergo sexual differentiation earlier in development than species with environmental sex determination (ESD). Most turtle species exhibit a form of ESD known as temperature-dependent sex determination (TSD), and in such species the chronology of sex differentiation is well studied. Apalone spinifera is a species of softshell turtle (Trionychidae) that exhibits GSD. We studied sexual differentiation in this species in order to facilitate comparison to TSD species. Eggs were incubated at two different temperatures and embryos were harvested at various stages of mid to late development. Gonad length was measured with image analysis software, then prepared histologically. Indifferent gonads have differentiated in stage 19 embryos. Histological details of gonadogenesis follow the same pattern as described for other reptiles. Regression of the male paramesonephric duct closely follows testicular differentiation. Gonad lengths are longer at the warmer incubation temperature, and ovaries are generally longer than testes at each stage and for each temperature. Although sexual differentiation takes place at about the same stage as in other turtles with TSD (18-20), in A. spinifera this differentiation is irreversible at this stage, while in some of the TSD species sex is reversible until about stage 22. This immutable, definitive sexual differentiation may support the hypothesis of an accelerated chronology of sex differentiation for this species. We also note that sexual dichromatism at hatching is known in this species and may provide additional evidence of early differentiation. J. Exp. Zool. 290:190-200, 2001., (Copyright 2001 Wiley-Liss, Inc.)

The identification of cis-sequences responsible for spatiotemporal patterns of gene expression often requires the functional analysis of large genomic regions. In this study a 100-kb zebrafish Hoxa-11b-lacZ reporter gene was constructed and expressed in transgenic mice. PAC clone 10-O19, containing a portion of the zebrafish HoxA-b cluster, was captured into the yeast-bacterial shuttle vector, pPAC-ResQ, by recombinogenic targeting. A lacZ reporter gene was then inserted in-frame into exon 1 of the zfHoxa-11b locus by a second round of recombinogenic targeting. Expression of the zfHoxa-11b-lacZ reporter gene in 10.5 d.p.f. transgenic mouse embryos was observed only in the posterior portion of the A-P axis, in the paraxial mesoderm, neural tube, and somites. These findings demonstrate the utility of recombinogenic targeting for the modification and expression of large inserts captured from P1/PAC clones.

We have developed a method to clone genomic DNA selectively into a yeast-bacterial shuttle vector, pClasper, by recombinogenic targeting in yeast. A gene-specific pClasper targeting vector was constructed with small recombinogenic ends (500 bp) derived from flanking sequences of the genomic region to be cloned. Linearized, recombinogenic pClasper targeting vector and native genomic DNA were cotransformed into yeast. The gene of interest is selectively cloned by recombination between the recombinogenic ends in the targeting vector and homologous regions in the genomic DNA. Here we demonstrate direct cloning of a stably integrated Hoxc8-LacZ-Ura3 reporter gene construct from a mouse embryo fibroblast cell line and single-copy genes from total human genomic DNA. The frequency of capture of the recombinant insert was 0.05-3% of transformants. In contrast to previous reports, we were able to clone genomic DNA directly with a vector containing yeast autonomous replicating sequences. This approach provides a powerful method with which to clone and modify genes precisely for functional analysis., (Copyright 1999 Academic Press.)

In this article, we consider the role of the Hox genes in chordate and vertebrate evolution from the viewpoints of molecular and developmental evolution. Models of Hox cluster duplication are considered with emphasis on a threefold duplication model. We also show that cluster duplication is consistent with a semiconservative model of duplication, where following duplication, one daughter cluster remains unmodified, while the other diverges and assumes a new architecture and presumably new functions. Evidence is reviewed, suggesting that Hox gene enhancers have played an important role in body plan evolution. Finally, we contrast the invertebrates and vertebrates in terms of genome and Hox cluster duplication which are present in the latter, but not the former. We question whether gene duplication has been important in vertebrates for the introduction of novel features such as limbs, a urogenital system, and specialized neuromuscular interactions.

We have developed a method to capture inserts from P1 and P1 artificial chromosome (PAC) clones into a yeast-bacteria shuttle vector by using recombinogenic targeting. We have engineered a vector, pPAC-ResQ, a derivative of pClasper, which was previously used to capture inserts from yeast artificial chromosome clones. pPAC-ResQ contains DNA fragments flanking the inserts in P1 and PAC vectors as recombinogenic ends. When linearized pPAC-ResQ vector and P1 or PAC DNA are cotransformed into yeast, recombination between the two leads to the transfer of inserts into pPAC-ResQ. pPAC-ResQ clones thus obtained can be further modified in yeast for functional analysis and shuttled to Escherichia coli to produce large quantities of cloned DNA. This approach provides a rapid method to modify P1/PAC clones for functional analysis., (Copyright 1999 Academic Press.)

Currently, recombinational cloning procedures based upon methods developed for yeast, Saccharomyces cerevisiae, are being exploited for targeted cloning and in-vivo modification of genomic clones. In this review, we will discuss the development of large-insert vectors, homologous recombination-based techniques for cloning and modification, and their application towards functional analysis of genes using transgenic mouse model systems.

The mammalian Hox clusters arose by duplication of a primordial cluster. The duplication of Hox clusters created redundancy within cognate groups, allowing for change in function over time. The lamprey, Petromyzon marinus, occupies an intermediate position within the chordates, both in terms of morphologic complexity and possibly cluster number. To determine the extent of divergence among Hox genes after duplication events within vertebrates, we analyzed Hox genes belonging to cognate group 8. Here we report characterization of the HoxQ8 gene, which shows conservation with mammalian genes in its amino-terminal, homeobox and hexapeptide sequences, and in the position of its splice sites. A beta-galactosidase reporter gene was introduced in the HoxQ8 genomic region by targeted recombinational cloning using a yeast-bacteria shuttle vector, pClasper. These reporter gene constructs were tested for their ability to direct region-specific expression patterns in transgenic mouse embryos. Lamprey enhancers direct expression to posterior neural tube but not to mesoderm, suggesting conservation of neuronal enhancers. In the presence of the mouse heat shock promoter, lamprey enhancers could also direct expression to the posterior mesoderm suggesting that there has been some divergence in promoter function. Our results suggest that comparative studies on Hox gene structure and analysis of regulatory elements may provide insights into changes concomitant with Hox cluster duplications in the chordates.

A heteromorphism in a pair of macrochromosomes in male Siebenrockiella crassicollis is interpreted as an XX/XY sex determining system. The heteromorphism involves a difference in centromere position and amount and distribution of heterochromatin. The only other sex chromosome system known in turtles is found in the kinosternid genus Staurotypus and is also an XX/XY system, but it involves a different chromosome pair and different chromosomal rearrangements. These two systems have independently arisen within the suborder Cryptodira and share no common ancestry. The sex chromosome system in Siebenrockiella represents a relatively early stage of differentiation. It differs from the hypothesized steps of differentiation in having a heterochromatically derived X.