Linking Theory to Practice in the Workplace

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The extragalactic radio-source population at 95 GHz

We have used the Australia Telescope Compact Array (ATCA) at 95GHz to carry out continuum observations of 130 extragalactic radio sources selected from the Australia Telescope 20GHz (AT20G) survey. Over 90% of these sources are detected at 95 GHz, and we use a triple-correlation method to measure simultaneous 20 and 95 GHz flux densities. We show that the ATCA can measure 95GHz flux densities to ~10% accuracy in a few minutes for sources above ~50mJy. The median 20-95GHz spectral index does not vary significantly with flux density for extragalactic sources with S20>150 mJy. This allows us to estimate the extragalactic radio source counts at 95GHz by combining our observed 20-95GHz spectral-index distribution with the accurate 20GHz source counts measured in the AT20G survey. The resulting 95GHz source counts down to 80 mJy are significantly lower than those found by several previous studies. The main reason is that most radio sources with flat or rising spectra in the frequency range 5-20GHz show a spectral turnover between 20 and 95 GHz. As a result, there are fewer 95GHz sources (by almost a factor of two at 0.1 Jy) than would be predicted on the basis of extrapolation from the source populations seen in lower-frequency surveys. We also derive the predicted confusion noise in CMB surveys at 95GHz and find a value 20-30% lower than previous estimates. The 95GHz source population at the flux levels probed by this study is dominated by QSOs with a median redshift z~1. We find a correlation between optical magnitude and 95GHz flux density which suggests that many of the brightest 95 GHz sources are relativistically beamed, with both the optical and millimetre continuum significantly brightened by Doppler boosting.Comment: Replaced with final version (MNRAS, in press), 15 pages plus two landscape data table

H2O2 Oxidation by Fe-III-OOH Intermediates and Its Effect on Catalytic Efficiency

The oxidation of the C-H and C=C bonds of hydrocarbons with H2O2 catalyzed by non-heme iron complexes with pentadentate ligands is widely accepted as involving a reactive Fe-IV=O species such as [(N4Py)Fe-IV=O](2+) formed by homolytic cleavage of the O-O bond of an Fe-III-OOH intermediate (where N4Py is 1,1-bis(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine). We show here that at low H2O2 concentrations the Fe-IV=O species formed is detectable in methanol. Furthermore, we show that the decomposition of H2O2 to water and O-2 is an important competing pathway that limits efficiency in the terminal oxidant and indeed dominates reactivity except where only sub-/near-stoichiometric amounts of H2O2 are present. Although independently prepared [(N4Py)Fe-IV=O](2+) oxidizes stoichiometric H2O2 rapidly, the rate of formation of Fe-IV=O from the Fe-III-OOH intermediate is too low to account for the rate of H2O2 decomposition observed under catalytic conditions. Indeed, with excess H2O2, disproportionation to O-2 and H2O is due to reaction with the Fe-III-OOH intermediate and thereby prevents formation of the Fe-IV=O species. These data rationalize that the activity of these catalysts with respect to hydrocarbon/alkene oxidation is maximized by maintaining sub-/near-stoichiometric steady-state concentrations of H2O2, which ensure that the rate of the H2O2 oxidation by the Fe-III-OOH intermediate is less than the rate of the O-O bond homolysis and the subsequent reaction of the Fe-IV=O species with a substrate

Maternal Environment Influences Cocaine Intake in Adulthood in a Genotype-Dependent Manner

Background: Accumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. However, direct evidence of such gene-environment interaction in the context of substance abuse is scarce. In the present study we investigated whether the impact of early life experiences on cocaine intake in adulthood depends on genetic background. In addition, we studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors. Methodology/Principal Findings: For this purpose, we manipulated the maternal environment of two inbred mouse strains, the C57BL/6J and DBA/2J by fostering them with non-related mothers, i.e. the C3H/HeN and AKR strains. These mother strains show respectively high and low pup-oriented behavior. As adults, C57BL/6J and DBA/2J were tested either for cocaine intravenous self-administration or in the elevated plus-maze and forced swim test (FST). We found that the impact of maternal environment on cocaine use and a depression-related behavior depends upon genotype, as cocaine self-administration and behavior in the FST were influenced by maternal environment in DBA/2J, but not in C57BL/6J mice. Anxiety was not influenced by maternal environment in either strain. Conclusions/Significance: Our experimental approach could contribute to the identification of the psychobiological factor

Cross-national epidemiology of DSM-IV major depressive episode

Background: Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low-to middle-income countries in the World Mental Health Survey Initiative. Methods: Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. Results: The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2: 1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low-to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. Conclusions: MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.(NIH/NIMH) United States National Institute of Mental Health[R01MH070884]John D. and Catherine T. MacArthur FoundationPfizer FoundationUSA Public Health Service[R13-MH066849]USA Public Health Service[R01-MH069864]USA Public Health Service[R01 DA016558](NIH) Fogarty International Center[FIRCA R03-TW006481]PAHO Pan American Health OrganizationEli Lilly & Company FoundationOrtho-McNeil Pharmaceutical, Inc.GlaxoSmithKlineSanofi-AventisBristol-Myers SquibbState of Brazil Research Foundation (FAPESP)[03/00204-3]Ministry of Social ProtectionEuropean Commission[QLG5-1999-01042]European Commission[SANCO 2004123]Piedmont Region (Italy)Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Spain[FIS 00/0028]Spanish Ministerio de Ciencia y Tecnologia[SAF 2000-158-CE]Departament de Salut, Generalitat de Catalunya, SpainInstituto de Salud Carlos III[CIBER CB06/02/0046]Instituto de Salud Carlos III[RETICS RD06/0011 REM-TAP]Government of IndiaWHOMinistry of HealthIsrael National Institute for Health Policy and Health Services ResearchNational Insurance Institute of IsraelJapan Ministry of Health, Labour and Welfare[H13-Shogai-023]Japan Ministry of Health, Labour and Welfare[H14-Tokubetsu-026]Japan Ministry of Health, Labour and Welfare[H16-Kokoro-013]Lebanese Ministry of Public HealthWHO (Lebanon)(NIH) Fogarty International, anonymous private donations to IDRAAC, LebanonJanssen CilagEli LillyRocheNovartisNational Institute of Psychiatry Ramon de la Fuente[INPRFMDIES 4280]CNPq National Council on Science and Technology[CONACyT-G30544-H]PanAmerican Health Organization (PAHO)New Zealand Ministry of Health, Alcohol Advisory CouncilHealth Research Council(NIH/NIMH) USA National Institute of Mental Health[R01-MH059575](NIH/NIMH) USA National Institute of Mental Health[RO1-MH61905]National Institute of Drug AbuseSouth African Department of HealthUniversity of MichiganNational Institute of Mental Health (NIH/NIMH)[U01-MH60220]National Institute of Drug Abuse (NIDA)Substance Abuse and Mental Health Services Administration (SAMHSA)Robert Wood Johnson Foundation (RWJF)[044708]John W. Alden TrustsAnalysis Group Inc.Eli Lilly CompanyEPI-QJohnson & Johnson PharmaceuticalsOrtho-McNeil Janssen Scientific AffairsPfizer Inc.Shire USA, Inc

The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive—despite the region’s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 569,000 deaths (95% UI 406,000–771,000) associated with bacterial AMR and 141,000 deaths (99,900–196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000–241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200–278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600–168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000–608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen–drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen–drug combination in 15 countries for deaths associated with AMR. Interpretation Given the burden across different countries, infectious syndromes, and pathogen–drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas.publishedVersio

The descriptive epidemiology of DSM-IV Adult ADHD in the World Health Organization World Mental Health Surveys

We previously reported on the cross-national epidemiology of ADHD from the first 10 countries in the WHO World Mental Health (WMH) Surveys. The current report expands those previous findings to the 20 nationally or regionally representative WMH surveys that have now collected data on adult ADHD. The Composite International Diagnostic Interview (CIDI) was administered to 26,744 respondents in these surveys in high-, upper-middle-, and low-/lower-middle-income countries (68.5% mean response rate). Current DSM-IV/CIDI adult ADHD prevalence averaged 2.8% across surveys and was higher in high (3.6%)- and upper-middle (3.0%)- than low-/lower-middle (1.4%)-income countries. Conditional prevalence of current ADHD averaged 57.0% among childhood cases and 41.1% among childhood subthreshold cases. Adult ADHD was significantly related to being male, previously married, and low education. Adult ADHD was highly comorbid with DSM-IV/CIDI anxiety, mood, behavior, and substance disorders and significantly associated with role impairments (days out of role, impaired cognition, and social interactions) when controlling for comorbidities. Treatment seeking was low in all countries and targeted largely to comorbid conditions rather than to ADHD. These results show that adult ADHD is prevalent, seriously impairing, and highly comorbid but vastly under-recognized and undertreated across countries and cultures

The pathophysiology of restricted repetitive behavior

Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson’s disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism