Reward-related attentional capture and cognitive inflexibility interact to determine greater severity of compulsivity-related problems.

BACKGROUND AND OBJECTIVES: Neurocognitive processes are key drivers of addictive and compulsive disorders. The current study examined whether reward-related attentional capture and cognitive inflexibility are associated with impulsive and/or compulsive personality traits, and whether these cognitive characteristics interact to predict greater compulsivity-related problems across obsessive-compulsive and drinking behaviors. METHODS: One-hundred and seventy-three participants (mean age = 34.5 years, S.D = 8.4, 42% female) completed an online visual search task to measure reward-related attentional capture and its persistence following reversal of stimulus-reward contingencies. Participants also completed questionnaires to assess trait impulsivity, compulsivity, alcohol use, and obsessive-compulsive behaviors. RESULTS: Greater reward-related attentional capture was associated with trait compulsivity, over and above all impulsivity dimensions, while greater cognitive inflexibility was associated with higher negative urgency (distress-elicited impulsivity). Reward-related attentional capture and cognitive inflexibility interacted to predict greater compulsivity-related problems among participants who reported obsessive-compulsive behaviors in the past month (n = 57) as well as current drinkers (n = 88). Follow-up analyses showed that, for OCD behaviors, this interaction was driven by an association between higher reward-related attentional capture and more problematic behaviors among cognitively inflexible participants only. For drinking, the same pattern was seen, albeit at trend level. LIMITATIONS: This study includes a non-clinical, online sample and is cross-sectional, thus its findings need to be interpreted with these limitations in mind. CONCLUSIONS: Reward-related attentional capture and cognitive flexibility are related to trait compulsivity and impulsivity (negative urgency) respectively, and interact to determine more problematic behaviors

Ozone depletion events observed in the high latitude surface layer during the TOPSE aircraft program

During the Tropospheric Ozone Production about the Spring Equinox (TOPSE) aircraft program, ozone depletion events (ODEs) in the high latitude surface layer were investigated using lidar and in situ instruments. Flight legs of 100 km or longer distance were flown 32 times at 30 m altitude over a variety of regions north of 58° between early February and late May 2000. ODEs were found on each flight over the Arctic Ocean but their occurrence was rare at more southern latitudes. However, large area events with depletion to over 2 km altitude in one case were found as far south as Baffin Bay and Hudson Bay and as late as 22 May. There is good evidence that these more southern events did not form in situ but were the result of export of ozone-depleted air from the surface layer of the Arctic Ocean. Surprisingly, relatively intact transport of ODEs occurred over distances of 900–2000 km and in some cases over rough terrain. Accumulation of constituents in the frozen surface over the dark winter period cannot be a strong prerequisite of ozone depletion since latitudes south of the Arctic Ocean would also experience a long dark period. Some process unique to the Arctic Ocean surface or its coastal regions remains unidentified for the release of ozone-depleting halogens. There was no correspondence between coarse surface features such as solid ice/snow, open leads, or polynyas with the occurrence of or intensity of ozone depletion over the Arctic or subarctic regions. Depletion events also occurred in the absence of long-range transport of relatively fresh “pollution” within the high latitude surface layer, at least in spring 2000. Direct measurements of halogen radicals were not made. However, the flights do provide detailed information on the vertical structure of the surface layer and, during the constant 30 m altitude legs, measurements of a variety of constituents including hydroxyl and peroxy radicals. A summary of the behavior of these constituents is made. The measurements were consistent with a source of formaldehyde from the snow/ice surface. Median NOx in the surface layer was 15 pptv or less, suggesting that surface emissions were substantially converted to reservoir constituents by 30 m altitude and that ozone production rates were small (0.15–1.5 ppbv/d) at this altitude. Peroxyacetylnitrate (PAN) was by far the major constituent of NOy in the surface layer independent of the ozone mixing ratio

Weltrohstoffversorgung: Konflikt oder Kooperation?

Unter dem Eindruck der jüngsten Preishausse auf den internationalen Rohstoffmärkten wird nunmehr in vielen Ländern befürchtet, daß die Welt an der Schwelle zunehmender Schwierigkeiten bei der Versorgung mit mineralischen und landwirtschaftlichen Rohstoffen einschließlich Nahrungsmitteln steht. Der kräftige Preisanstieg bei diesen Rohstoffen war jedoch überwiegend konjunkturell bedingt. Bei Getreide verursachten Mißernten unerwartete Produktionsausfälle größeren Ausmaßes. Wirksame Preisabsprachen zwischen Produzentenländern hat es, anders als bei Erdöl, entgegen einer verbreiteten Meinung nicht gegeben. Längerfristig wird sich das Preisniveau auf den Rohstoffmärkten, wenn auch nicht drastisch, so doch kontinuierlich erhöhen. Preisfluktuationen um den Trend werden weiterhin diese Märkte kennzeichnen. Ernsthafte Rohstoffverknappungen brauchen für den Rest dieses Jahrhunderts nicht erwartet zu werden. So übersteigen z. B. im Falle zahlreicher nicht-regenerierbarer NE-Metalle die bekannten Weltreserven deutlich den Weltbedarf; bei tropischen Ernährungsgütern und bei Getreide ist der Spielraum für eine nachhaltige Erhöhung der Flächenerträge noch sehr groß, vor allem in Entwicklungsländern. Die Wahrscheinlichkeit für die Bildung von Produzentenkartellen in der Zukunft ist gering. Käme es dennoch zu Kartellabsprachen, so wären diese bestenfalls kurzfristig erfolgreich. Das gleiche gilt für Exportbeschränkungen, die in Zeiten knappen Angebots sensibler Produkte (z. B. Getreide) den internen Preisanstieg dämpfen sollen. Angesichts der verbreiteten Knappheitspsychose kann nicht ausgeschlossen werden, daß es im Falle von temporären Angebotsdefiziten zu Überreaktionen kommt, die erhebliche Gefahren für den freien und multilateralen Welthandel in sich bergen. Solchen Gefahren kann nur erfolgreich durch partnerschaftliche Zusammenarbeit, nicht jedoch durch nationale Alleingänge, begegnet werden. Erforderlich sind ein international vereinbartes System von Verhaltensregeln zur Sicherung des undiskriminierten Zugangs zu Rohstoffmärkten bei angemessenen Preisen, die koordinierte Bildung von Rohstoffvorräten, internationale Rohstoffabkommen zwischen Produzenten- und Verbraucherländern, Regelungen zur Verbesserung des allgemeinen Investitionsklimas im Rohstoffbereich und der Abbau der Handelsschranken der Industrieländer gegenüber Exporten landwirtschaftlicher Produkte sowie rohstoff- und/oder arbeitsintensiver Halb- und Fertigwaren aus Entwicklungsländern. --

Welthandel und Strukturanpassung in den Industrieländern

Ziel der sechsten GATT-Runde ist es, die Schranken im Welthandel weiter abzubauen. Anders als bei den fünf früheren GATT-Runden herrscht dieses Mal in vielen Ländern Skepsis gegenüber einer weiteren Liberalisierung, weil man die Risiken, die mit zunehmendem Importwettbewerb verbunden sein können, höher bewertet als die möglichen Vorteile der Liberalisierung. Das Aufrechterhalten von Handelsschranken kostet Ressourcen. Die Protektion wenig effizienter Industrien in den wohlhabenden Ländern hält deren Einkommen unter dem Niveau, das sie sonst erreichen könnten und verzögert das Tempo der Industrialisierung in den Entwicklungsländern. Die ökonomischen Argumente zugunsten eines freieren Handels sind stark und weitgehend unanfechtbar. Handelsbeschränkungen sind zudem politisch belastend. Es gibt eine Reihe staatlicher Maßnahmen, die geeignet sind, die Schocks einer Anpassung an wirtschaftliche Veränderungen zu mindern. Interne Anpassungmaßnahmen spielen daher eine bedeutende Rolle in der künftigen Handelspolitik. Sehr zweifelhaft ist, ob alle Möglichkeiten für wirksame Anpassungsmaßnahmen bereits ausgeschöpft sind. In der Textilindustrie, der Stahlindustrie und im Kohlenbergbau existieren nach allgemeiner Meinung hartnäckige Anpassungsprobleme, die besondere und permanente Schutzmaßnahmen gegen den Importwettbewerb verlangen. Obwohl es viele Anstrengungen gegeben hat, den Status quo aufrechtzuerhalten, hat in allen drei Fällen die Dynamik des Strukturwandels die Lage grundlegend verändert. Diese Entwicklungstendenzen erlauben den Schluß, daß weitere Schritte zur Liberalisierung auch in den schwierigsten Fällen nicht nur wünschenswert wären, sondern wahrscheinlich durch den immanenten Strukturwandel in der Wirtschaft erleichtert werden. Eine Veränderung ist selten bequem, selbst dann nicht, wenn sie zu Verbesserungen führt. Für die Politik darf die relevante Frage nicht sein, wie man eine Anpassung an veränderte Umstände verlangsamen oder verhindern könnte. Sie lautet vielmehr, wie man die Chancen, die ein freierer Handel bietet, dadurch nutzen kann, daß man die Anpassung erleichtert und ihre Kosten minimiert. --

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treating Uncomplicated Malaria: A Randomized Trial to Guide Policy in Uganda

BACKGROUND: Uganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission. METHODOLOGY/PRINCIPAL FINDINGS: Patients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0-28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI -0.2-7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated. CONCLUSIONS/SIGNIFICANCE: DP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN75606663

MINDS. Abundant water and varying C/O across the disk of Sz 98 as seen by JWST/MIRI

MIRI/MRS on board the JWST allows us to probe the inner regions of protoplanetary disks. Here we examine the disk around the classical T Tauri star Sz 98, which has an unusually large dust disk in the millimetre with a compact core. We focus on the H$_2$O emission through both its ro-vibrational and pure rotational emission. Furthermore, we compare our chemical findings with those obtained for the outer disk from Atacama Large Millimeter/submillimeter Array (ALMA) observations. In order to model the molecular features in the spectrum, the continuum was subtracted and LTE slab models were fitted. The spectrum was divided into different wavelength regions corresponding to H$_2$O lines of different excitation conditions, and the slab model fits were performed individually per region. We confidently detect CO, H$_2$O, OH, CO$_2$, and HCN in the emitting layers. The isotopologue H$^{18}_2$O is not detected. Additionally, no other organics, including C$_2$H$_2$, are detected. This indicates that the C/O ratio could be substantially below unity, in contrast with the outer disk. The H$_2$O emission traces a large radial disk surface region, as evidenced by the gradually changing excitation temperatures and emitting radii. The OH and CO$_2$ emission are relatively weak. It is likely that H$_2$O is not significantly photodissociated; either due to self-shielding against the stellar irradiation, or UV-shielding from small dust particles. The relative emitting strength of the different identified molecular features point towards UV-shielding of H$_2$O in the inner disk of Sz 98, with a thin layer of OH on top. The majority of the organic molecules are either hidden below the dust continuum, or not present. In general, the inferred composition points to a sub-solar C/O ratio (<0.5) in the inner disk, in contrast with the larger than unity C/O ratio in the gas in the outer disk found with ALMA.Comment: Submitted to A&A on May 25 2023. 18 pages, 11 figure

MINDS. The detection of 13^{13}CO2_{2} with JWST-MIRI indicates abundant CO2_{2} in a protoplanetary disk

We present JWST-MIRI MRS spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey (MINDS) GTO program. Emission from $^{12}$CO$_{2}$, $^{13}$CO$_{2}$, H$_{2}$O, HCN, C$_{2}$H$_{2}$, and OH is identified with $^{13}$CO$_{2}$ being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few au of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The $Q$-branches of these molecules, including those of hot-bands, are particularly sensitive to temperature and column density. We find that the $^{12}$CO$_{2}$ emission in the GW Lup disk is coming from optically thick emission at a temperature of $\sim$400 K. $^{13}$CO$_{2}$ is optically thinner and based on a lower temperature of $\sim$325 K, may be tracing deeper into the disk and/or a larger emitting radius than $^{12}$CO$_{2}$. The derived $N_{\rm{CO_{2}}}$/$N_{\rm{H_{2}O}}$ ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on \textit{Spitzer}-IRS data. This high column density ratio may be due to an inner cavity with a radius in between the H$_{2}$O and CO$_{2}$ snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.Comment: 15 pages, 10 figures. Accepted to ApJ

Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

BACKGROUND: New antimalarial regimens, including artemisinin-based combination therapies (ACTs), have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. CASE DESCRIPTION: Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. DISCUSSION AND EVALUATION: Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. CONCLUSION: Although the World Health Organization has supported the development of pharmacovigilance systems in African countries deploying ACTs, additional guidance on adverse events monitoring in antimalarial clinical trials is needed, similar to the standardized recommendations available for assessment of drug efficacy

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease