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Copyright of Revista Brasileira de Políticas Públicas is the property of Revista Brasileira de Politicas Publicas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The design, development, and successful implementation of pop-up Langmuir probes installed in the water-cooled divertor of W7-X are described. The probes are controlled by drive coils (actuators) installed behind the divertor plates. These drive coils make use of the magnetic field in W7-X to move the probe tips into and out of the plasma. The drive coils were installed in the vacuum vessel after extensively testing the durability of the coils and analyzing the criteria for safe operation. The probe design is carefully tailored for each of the 36 probe tips in order to be suitable for the different magnetic field configurations used in W7-X and ensure that the probes do not present leading edges to the magnetic flux tubes. An electronic bridge circuit is used for measurement to compensate for the effects of signal propagation time on the long cable lengths used. The diagnostic is integrated with the segment control of W7-X for automated operation and control of the diagnostic. The evaluation of the results from the plasma operation is presented after accounting for appropriate sheath expansion for negative bias voltage on the probes. [ABSTRACT FROM AUTHOR]

Joyce Marie Mushaben, What Remains? The Dialectical Identities of Eastern Germans (Cham, Switzerland: Palgrave Macmillan, 2023) Ruud Koopmans, Die Asyl-Lotterie: Eine Bilanz der Flüchtlingspolitik von 2015 bis zum Ukraine-Krieg (München: C.H. Beck, 2023) Jane Freeland, Feminist Transformations and Domestic Violence in Divided Berlin, 1968–2002 (Oxford: Oxford University Press, 2022) Florian Grotz and Wolfgang Schroeder, The Political System of Germany (Cham: Palgrave Macmillan, 2023) Paul Carls, Multiculturalism and the Nation in Germany: A Study in Moral Conflict (New York: Routledge, 2023) Julia E. Ault, Saving Nature Under Socialism: Transnational Environmentalism in East Germany, 1968–1990 (Cambridge: Cambridge University Press, 2021) [ABSTRACT FROM AUTHOR]

What does right-wing populism look like in Luxembourg, a small European state whose economy heavily relies on strong European integration and foreign and cross-border labor? This article explores this question by looking at the Alternativ Demokratesh Reformpartei (ADR), Luxembourg's version of a right-wing populist party. It studies the ADR's discourse during three discursive events: the debate over a burka law (2014–2018), the 2015 Refugee Crisis, and Luxembourg's 2015 constitutional referendum. Much of the ADR's discourse is right-wing populist, but with two specificities: the ADR's embrace of multiculturalism and its use of the issue of the national language to appeal to cultural and economic interests. Both of these specificities reflect into a distinctive concept of the Luxembourgish 'people'. The Luxembourg case demonstrates the chameleonic nature or populism, or its ability to adapt to its local circumstances, in this instance even adopting features that contradict much of the thinking on right-wing populism. [ABSTRACT FROM AUTHOR]

Octopuses are highly intelligent animals with vertebrate-like cognitive and behavioural repertoires. Despite these similarities, vertebrate-based models of cognition and behaviour cannot always be successfully applied to octopuses, due to the structural and functional characteristics that have evolved in their nervous system in response to the unique challenges posed by octopus morphology. For instance, the octopus brain does not support a somatotopic or point-for-point spatial map of the body—an important feature of vertebrate nervous systems. Thus, while octopuses are capable of motor tasks whose vertebrate counterparts require detailed interoceptive monitoring, these movements may not be explainable using motor control frameworks premised on internal spatial representation. One such motor task is the extension of a single arm. The ability of octopuses to select and use a single arm without the guidance of a somatotopic map has been regarded as a motor control puzzle. In an attempt at a solution, this paper develops a predictive processing account of single-arm extension in octopuses. [ABSTRACT FROM AUTHOR]

Copyright of Wirtschafts- und Sozialwissenschaftliches Institut Mitteilungen is the property of Nomos Verlagsgesellschaft mbH & Co. KG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper addresses an important yet neglected existential issue sometimes faced by persons with bipolar disorder (BD): confusion about the extent to which what one is like is influenced by BD. Although such confusion is common in psychiatric illnesses, BD raises idiosyncratic difficulties due to its intricate interactions with personality, cognition and behavior. The fluctuating mood phases of BD can generate inconsistency in one's self-experience and sense of self. One way to resolve this confusion would be to coherently account for BD within one's overall self-concept. To facilitate this task, this paper introduces a heuristic taxonomy of different relationships wherein BD can be viewed in light of self-related beliefs. The relationships are as follows: (1) BD contributes to the self, (2) BD scaffolds the self, (3) BD gradually becomes part of the self and (4) BD is not part of the 'real self'. As the individual presentation of BD varies extensively, the type of relationship one feels holds true depends on one's personal experience of managing and living with the disorder. These relationships act as an organizing framework for one's self-related beliefs about how to account for the effects of BD on personality, behavior, cognitive patterns and other self-expressions. [ABSTRACT FROM AUTHOR]

Among the Mercosur countries (Argentina, Brazil, Paraguay and Uruguay), the free trade agreement between them and Singapore reveals Brazil's clear interest in expanding economic and trade relations with key players in Asia, a highly dynamic trading area. [ABSTRACT FROM AUTHOR]

Much of the literature on the free energy principle (FEP) has focused on how organisms maintain homeostasis amidst a constantly changing environment. A fundamental feature of the FEP is that biological entities are “hard-wired” towards self-preservation. However, contrary to this notion, there do exist organisms that appear to seek out rather than avoid conditions that pose an elevated risk of serious injury or death, thereby jeopardizing their physiological integrity. Borrowing a term used in 1990s popular culture to refer to stunt performers like Evel Knievel, these organisms that exhibit such behavioural characteristics can be referred to as daredevils. This paper presents the case of daredevils as a challenge to the FEP’s homeostasis- and optimization-based construal of biological systems. It also introduces three possible explanatory strategies by which the FEP can account for daredevils. The broader objective of the paper is to enhance the FEP’s ability to account for a diverse range of complex behaviour. [ABSTRACT FROM AUTHOR]

Recurrent, unvarying, and seemingly purposeless patterns of action and cognition are part of normal development, but also feature prominently in several neuropsychiatric conditions. Repetitive stereotyped behaviors (RSBs) can be viewed as exaggerated forms of learned habits and frequently correlate with alterations in motor, limbic, and associative basal ganglia circuits. However, it is still unclear how altered basal ganglia feedback signals actually relate to the phenomenological variability of RSBs. Why do behaviorally overlapping phenomena sometimes require different treatment approaches-for example, sensory shielding strategies versus exposure therapy for autism and obsessive-compulsive disorder, respectively? Certain clues may be found in recent models of basal ganglia function that extend well beyond action selection and motivational control, and have implications for sensorimotor integration, prediction, learning under uncertainty, as well as aesthetic learning. In this paper, we systematically compare three exemplary conditions with basal ganglia involvement, obsessive-compulsive disorder, Parkinson's disease, and autism spectrum conditions, to gain a new understanding of RSBs. We integrate clinical observations and neuroanatomical and neurophysiological alterations with accounts employing the predictive processing framework. Based on this review, we suggest that basal ganglia feedback plays a central role in preconditioning cortical networks to anticipate self-generated, movement-related perception. In this way, basal ganglia feedback appears ideally situated to adjust the salience of sensory signals through precision weighting of (external) new sensory information, relative to the precision of (internal) predictions based on prior generated models. Accordingly, behavioral policies may preferentially rely on new data versus existing knowledge, in a spectrum spanning between novelty and stability. RSBs may then represent compensatory or reactive responses, respectively, at the opposite ends of this spectrum. This view places an important role of aesthetic learning on basal ganglia feedback, may account for observed changes in creativity and aesthetic experience in basal ganglia disorders, is empirically testable, and may inform creative art therapies in conditions characterized by stereotyped behaviors. [ABSTRACT FROM AUTHOR]

Émile Durkheim's late work focuses on représentations collectives, social facts that embody sui generis social forces and that direct behaviour in meaningful ways. The focus on représentations collectives raises questions, but also opens doors for Durkheimian sociology. Many would contend that Durkheim's focus on représentations collectives introduces a hermeneutical and ideational element that is at odds with his positivist approach. His study of représentations collectives also point to a potentially broad application of his method to the study of culture as a causally autonomous factor in social life. This article will discuss the social fact in Durkheim's late work in light of these issues. It will argue that représentations collectives are social facts, 'things' in Durkheim's terminology, that are rooted in ritual. They have an objective existence and are causally efficacious, which makes them the object of positive sociology; there is thus no tension between 'early' and 'late' Durkheim on this point. It will also argue that due to the causally autonomous and inherently meaningful nature of représentations collectives, Durkheim's approach adds to the Strong Program's research agenda, albeit with more of a focus on ritual and emotional energy. In so doing the article seeks to build a bridge between the Strong Program and the interaction ritual approach developed by Randall Collins. [ABSTRACT FROM AUTHOR]

The cognitive capacities and behavioural repertoire of octopuses have led to speculation that these animals may possess consciousness. However, the nervous system of octopuses is radically different from those typically associated with conscious experience: rather than being centralised and profoundly integrated, the octopus nervous system is distributed into components with considerable functional autonomy from each other. Of particular note is the arm nervous system: when severed, octopus arms still exhibit behaviours that are nearly identical to those exhibited when the animal is intact. Given these factors, there is reason to speculate that if octopuses do possess consciousness, it may be of a form highly dissimilar to familiar models. In particular, it may be that the octopus arm is capable of supporting an idiosyncratic field of consciousness. As such, in addition to the likelihood that there is something it is like to be an octopus, there may also be something it is like to be an octopus arm. This manuscript explores this possibility. [ABSTRACT FROM AUTHOR]

Of the modalities through which self-recognition is believed to be implemented, philosophical literature on the subject is most familiar with vision and interoception. However, they are not the only ones: chemoreception is another modality that biologists have found to be a contributor to self-recognition in numerous species, of which arthropods are notable. This article aims to help address the gap between philosophical and biological literature by presenting the octopus as an example of a creature in which peripheral chemoreceptive processes appear to be a significant component of self-recognition. Building on the findings of Nesher et al. that chemical compounds in octopus skin interfere with the behaviour of its suckers, this article proffers an account of how chemoreception may contribute to self-recognition in octopuses. [ABSTRACT FROM AUTHOR]

After 25 years of the TRIPS Agreement, it is time to look at the Brazilian GI system and how it has developed since its establishment. GIs under TRIPS might not be the universal consensus, but they formed the starting point for the Brazilian GI system, and since 1996 GIs are expressly mentioned as such in domestic legislation. The article analyses the Brazilian GI journey from TRIPS to today's framework, and points out the challenges that are yet to be faced at domestic, regional and international level. [ABSTRACT FROM AUTHOR]

The magnet system of the stellarator fusion device Wendelstein 7-X (W7-X) is composed of three different groups of coil systems. The main magnetic field is created by a superconducting magnet system that is accompanied by two sets of normal conducting coil groups, the trim coils positioned outside of the cryostat and the control coils (CCs) inside the plasma vessel. The CC system consists of ten 3-D shaped coils, power supplies, cooling systems, high current feeds, and an autonomous remote control system. The coils are situated behind the baffle plates of the ten divertor units. The magnetic field created by the CC system allows for the correction of error fields to influence the islands at the plasma boundary and for the sweeping of the separatrix, e.g., the point of the largest power position across the divertor. At the end of 2015, the installation of the CC system was completed and the integral commissioning took place in parallel with the ongoing completion of W7-X. For the first time, the CCs and their power supply were operated in conjunction with all auxiliary systems like the power distribution system, the high current feeds, the interspace vacuum system, the cooling system, and the safety control system. This article describes the results obtained and experiences gained during the integral commissioning of the CC system, including the baking process in preparation for the first experimental campaign of W7-X. [ABSTRACT FROM AUTHOR]

Copyright of Tematy & Konteksty is the property of University of Rzeszow and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To review the way consciousness is operationalised in contemporary research, discuss strengths and weaknesses of current approaches and propose new measures. Method: We first reviewed the literature pertaining to the phenomenal character of visual and self‐consciousness as well as awareness of visual stimuli. We also reviewed more problematic cases of dreams and animal consciousness, specifically that of octopuses. Results: Despite controversies, work in visual and self‐consciousness is highly developed and there are notable successes. Cases where experiences are not induced, such as dreams, and where no verbal report is possible, such as when we study purported experiences of octopuses, are more challenging. It is difficult to be confident about the reliability and validity of operationalisations of dreams. Although this is a general concern about the measuring consciousness, it is not a sufficiently severe concern to completely undermine the work reviewed on vision and self‐consciousness. It is more difficult to see how the good work on human psychology can be applied to non‐human animals, especially those with radically different nervous systems, such as octopuses. Given the limitations of report‐based operationalisations of consciousness, it is desirable to develop non‐report‐based measures, particularly for phenomenal qualities. We examine a number of possibilities and offer two possible approaches of varying degrees of practicality, the first based on combining quality space descriptions of phenomenal qualities and the notion of a "neural activation space" inherited from connectionist A.I., the second being a novel match to target approach. Conclusion: Consciousness is a multi‐faceted phenomenon and requires a variety of operationalisations to be studied. [ABSTRACT FROM AUTHOR]

The idea that there can be only one cognitive system within any single given cognitive organism is an established albeit implicit one within cognitive science and related studies of the mind. The firm foothold of this notion is due largely to the immense corpus of empirical evidence for the correlation of a high level of cognitive sophistication with a centralized nervous system. However, it must be pointed out that these findings are sourced in large part from studies on vertebrates. This paper presents a potential counterexample to the notion that only one cognitive system can be realized within any single genuine cognitive organism. This counterexample is the octopus, an invertebrate with what initially appears to be a paradoxical combination of vertebrate-like cognitive and behavioral capacities and a functionally decentralized nervous system. The extensive relegation of sensorimotor processing and control responsibilities to the peripheral nervous system which controls the arms of the octopus raises principled reasons to believe that the octopus is an organism that may house multiple independent cognitive systems. [ABSTRACT FROM AUTHOR]

Low commodity prices combined with high input costs have deteriorated net farm income over the last several years. As a result, management decisions have become extremely important, as any less than optimal decision could result in the farm losing money. Understanding which factors of production have the greatest effect on net farm income can help producers focus their efforts. This study analyzed various factors affecting net farm income to determine those that were most important to the profitability of an operation. Results varied depending upon the set of years analyzed and the region of the state. This may reflect an environment where the factors important to a top farm vary by the overall condition of the farm economy. [ABSTRACT FROM AUTHOR]

Posaconazole prophylaxis is recommended for patients with acute myeloid leukaemia during induction chemotherapy. Although a tablet formulation with better oral bioavailability is available, some patients have to rely on the oral suspension in clinical routine. Therefore, effectiveness of posaconazole oral suspension under real‐life clinical conditions and impact of patient education about the correct intake on its plasma concentrations were assessed in this study. Altogether 96 patients receiving 160 cycles of induction chemotherapy were retrospectively (40 patients) and prospectively (56 patients) analysed. Patients were assigned into two groups for each chemotherapy cycle according to the application of antifungal prophylaxis (A: posaconazole oral suspension, 200 mg three times a day ≥7 days; B: intake <7 days, fluconazole or no prophylaxis). Antifungal prophylaxis and therapy were analysed for each cycle. Additionally, plasma concentrations were determined from prospectively included subjects of group A who were intensively educated to perform a correct drug intake. Systemic antifungal therapy was statistically started less often in group A (26% vs 53%; P = 0.002). Posaconazole prophylaxis was associated with a lower risk of proven invasive fungal infection (P = 0.003). Median plasma concentration apparently increased between the first and second time of determination effected by an initial intensive on‐site patient education. The clinical effectiveness of posaconazole oral suspension was confirmed. A detailed patient education at the beginning of the treatment with posaconazole oral suspensions seems to be of primary importance for efficient plasma concentrations. [ABSTRACT FROM AUTHOR]

The largest modular stellarator Wendelstein 7-X (W7-X) has successfully passed the first phase of operation in Greifswald, Germany. The sophisticated W7-X superconducting magnet system (MS) with its nonlinear support system has been carefully monitored using an extensive set of mechanical and temperature sensors. This paper focuses on detailed consideration of cyclic MS behavior during operation with limiter configurations of plasma. Measurement results are carefully compared with predictions from updated numerical models and critical issues are highlighted. As a result, the structural monitoring tool is extended to follow enhanced requirements and expectations. This paper is a preparation for upcoming more demanding phases with longer plasma pulses to guarantee safe and reliable W7-X operation with different divertor and scraper element configurations. The procedure to establish required sensor configurations, and to analyze and release new plasma regimes being compatible with W7-X component design values is also described. [ABSTRACT FROM AUTHOR]

Aims: To evaluate treatment satisfaction in patients with type 2 diabetes (T2D) not adequately controlled by metformin, randomized to ITCA 650 (continuous exenatide in osmotic mini‐pump) vs twice‐daily exenatide injections (Ex‐BID). Materials and methods: The Diabetes Medication Satisfaction Tool (DM‐SAT) was administered and assessments were made at baseline, Week 8 and Week 20 during a 24‐week open‐label phase 2 trial. In Stage I (Weeks 1‐12), 155 patients, comprising the ITT population, were randomized to 3 groups: ITCA 650 20 μg/day, ITCA 650 40 μg/day and Ex‐BID 10 μg BID. In Stage II (Weeks 13‐24), ITCA 650 groups were re‐randomized to either remain on the Stage I dose or receive a higher dose. Patients treated with Ex‐BID were randomized to 40 or 60 μg/day ITCA 650. Results: Patients using ITCA 650 reported significant increases in overall treatment satisfaction by Week 8 vs those using Ex‐BID (P < .01), despite similar clinical efficacy and overall rates of nausea. During Stage II, further improvement in HbA1c and weight were seen after 3‐fold dose escalation of ITCA 650 and treatment satisfaction was maintained. When patients using Ex‐BID were switched to ITCA 650, treatment satisfaction increased and reached levels similar to those initially treated with ITCA 650. Neither GI side effects of nausea and/or vomiting, nor the procedure to sub‐dermally place ITCA 650, significantly impacted treatment satisfaction scores. Conclusion: ITCA 650 added to metformin for patients with T2D, and for those who switched to ITCA 650 from Ex‐BID, meaningfully improved glucose control and significantly increased overall treatment satisfaction. [ABSTRACT FROM AUTHOR]

Whichever side of the debate one chooses, plant sentience is a fertile research area that challenges received views and assumptions, generates novel insights, and suggests new ways that felt states might arise. My commentary discusses methodological and philosophical implications. [ABSTRACT FROM AUTHOR]

If the octopus were conscious, what would its consciousness be like? This paper investigates the structure octopus consciousness, if existent, is likely to exhibit. Presupposing that the configuration of an organism’s consciousness is correlated with that of its nervous system, it is unlikely that the structure of the sort of conscious experience that would arise from the highly decentralized octopus nervous system would bear much resemblance to those of vertebrates. In particular, octopus consciousness may not exhibit unity, which has long been assumed to be the normal or default structure of consciousness. The octopus nervous system is characterized by the following features: its three anatomically distinct components have extensive functional autonomy and little intercommunication; much of the sensory processing and motor control routines—that in vertebrates are localized in the brain—take place within the peripheral arm nervous system; and proprioception and somatotopic representation (point-for-point mapping of the body) are significantly downplayed. In this paper, I present the octopus as a highly successful biological organism in which it is plausible that the unified model of consciousness does not hold. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications.Research Design and Methods: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide 1 receptor agonist (GLP-1 RA) or dipeptidyl peptidase 4 (DPP-4) inhibitor with published findings from randomized controlled trials (RCTs) evaluating these drugs. Selected RW patients were similar to RCT patients, and regression analysis was used in the RW data to adjust for differences between poorly adherent and adherent patients to explain why RCT and RW findings may differ.Results: RW patients initiating a GLP-1 RA (n = 221) or a DPP-4 (n = 652) experienced smaller reductions in HbA1c (GLP-1 RA: -0.52% [-6 mmol/mol], DPP-4: -0.51% [-6 mmol/mol])than reported in RCTs (-1.30% [-14 mmol/mol] from seven GLP-1 RA RCTs, n = 2,600; -0.68% [-8 mmol/mol] from four DPP-4 RCTs, n = 1,889). Baseline HbA1c, additional medications, and adherence were significant explanatory factors in the RW HbA1c change. Modeled estimates of RCT efficacy (-1.04% GLP-1 RA [-12 mmol/mol], -0.69% DPP-4 [-8 mmol/mol]) were within the RCTs' reported range (GLP-1 RA: -0.84% to -1.60% [-9 to -18 mmol/mol], DPP-4: -0.47% to -0.90% [-5 to -10 mmol/mol]). Poor medication adherence accounted for approximately three-fourths of the gap between RW and expected RCT results (gap = 0.51% [6 mmol/mol] GLP-1 RA; 0.18% [3 mmol/mol] DPP-4).Conclusions: Poor medication adherence is primarily why RW effectiveness is significantly less than RCT efficacy, suggesting an urgent need to effectively address adherence among patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Previous research has found that the percentage of US adults with diabetes achieving a glycated hemoglobin (HbA1c) target of <7.0% with currently available treatments has been fairly constant from 2003 to 2010, remaining at just over 50% [1]. The objective of this study was to compare the most recent data (2011-2014) with earlier data to track progress on HbA1c target achievement, for both the general target of <7.0% and inferred individualized targets based on age and the presence of complications. Methods: Data from 2677 adults with self-reported diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014 were examined to determine the percentage of adults who achieved HbA1c targets of <7% and an individualized target based on age and comorbidities. National estimates are reported by using weights that account for the complex sampling design of the NHANES. Results: The percentage of people with diabetes and HbA1c <7.0% slightly declined from 52.2% (95% CI 48.7-55.7%) to 50.9% (95% CI 47.2-54.7%) between the two most recent waves of data. Achievement of individualized targets declined from 69.8% (95% CI 66.5-73.0%) to 63.8% (95% CI 60.1-67.5%). The percentage with HbA1c >9.0% increased from 12.6% (95% CI 10.5-14.8%) to 15.5% (95% CI 12.9-18.2%). Achievement of individualized targets varied by age group and presence of comorbidities, but exhibited similar trends as general target achievement. Conclusions: Despite the development of many new medications to treat diabetes during the past decade, the proportion of patients achieving glycemic control targets has not improved. Funding: Intarcia Therapeutics. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) from creosote exposure in the laboratory resulted in deleterious effects in developing Pacific herring ( Clupea pallasi) embryos, and potentially toxic concentrations of PAHs were measured using passive water samplers at 1 of 3 harbor field sites in Juneau, Alaska, USA. Aqueous total PAH concentrations of 4.6 μg/L and 8.4 μg/L from creosote exposure resulted in skeletal defects and ineffective swimming in hatched larvae in the laboratory (10% effective concentrations) and were the most sensitive parameters measured. Hatch rates also suffered from creosote exposure in a dose-dependent manner: at exposures between 5 μg/L and 50 μg/L total PAH, 50% of the population failed to hatch. Comparisons between laboratory and field deployed passive samplers suggested that for at least 1 harbor in Juneau, concentrations sufficient to induce teratogenic effects were found directly on creosoted pilings, within 10 cm of them, and sometimes at a distance of 10 m. Total PAH concentrations generally decreased with distance from creosoted pilings. Creosote pilings contribute to the PAH load within a marina and can rise to PAH concentrations that are harmful to fish embryos, but at a scale that is localized in the environment. Environ Toxicol Chem 2017;36:1261-1269. © 2016 SETAC [ABSTRACT FROM AUTHOR]

Voriconazole is both a substrate and a potent inhibitor of cytochrome P450 (CYP) 3A. It has a high bioavailability and non-linear pharmacokinetics. We investigated the pharmacokinetics and metabolism of 50 mg and 400 mg doses of intravenous and oral voriconazole in 14 healthy volunteers. Concurrently, we determined systemic and presystemic CYP3A activity with microdosed midazolam. Bioavailability of voriconazole 50 mg was 39 % compared with 86 % of the 400 mg dose. Voriconazole area under the concentration-time curve extrapolated to infinity (AUC∞) was 416 and 16,700 h·ng/mL for the 50 and 400 mg oral doses, respectively, and 1110 and 19,760 h·ng/mL for the 50 and 400 mg intravenous doses, respectively. Midazolam metabolism was dose-dependently inhibited by voriconazole. Dose-dependent autoinhibition of CYP3A-dependent first-pass metabolism and systemic metabolism is a possible explanation for the dose-dependent bioavailability and elimination of voriconazole, either as additional mechanism to, or instead of, saturation of presystemic metabolism. Higher bioavailability and non-linear pharmacokinetics are expected to be a common property of drugs that are substrates and inhibitors of CYP3A, e.g. clarithromycin. [ABSTRACT FROM AUTHOR]

Background: Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy.Methods and Findings: Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown.Conclusion: This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications. [ABSTRACT FROM AUTHOR]

Over the past quarter century, petroleum biomarkers have persisted in sequestered Exxon Valdez oil in Prince William Sound and the Gulf of Alaska (USA), and hence the oil has remained identifiable. These biomarkers are molecular fossils derived from biochemicals in previously living organisms. Novel pattern matching indicated the presence of Alaska North Slope crude oil (ANSCO) over the entire observation period at most sites (7 of 9) and distinguished this source from several other potential sources. The presence of ANSCO was confirmed with Nordtest forensics, demonstrating the veracity of the new method. The principal advantage of the new method is that it provides sample-specific identification, whereas the Nordtest approach is based on multisample statistics. Biomarkers were conserved relative to other constituents, and thus concentrations (per g oil) in initial beach samples were greater than those in fresh oil because they were lost more slowly than more labile oil constituents such as straight-chain alkanes and aromatic hydrocarbons. However, biomarker concentrations consistently declined thereafter (1989-2014), although loss varied substantially among and within sites. Isoprenoid loss was substantially greater than tricyclic triterpane, hopane, and sterane loss. Environ Toxicol Chem 2016;35:2683-2690. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and as such, is in the public domain in the United States of America. [ABSTRACT FROM AUTHOR]

Interactive website charts can be used to engage stakeholders and help them understand and apply relevant data. We explain methods we used to create and implement interactive charts for online outreach so that other Extension personnel can use similar interactive tools with their clientele. We describe step by step and in detail how we made interactive graphs and embedded them in a website. We also explain why we chose to use Google Docs as the source for this effort. Our approach offers a useful way to disseminate beneficial information to Extension clients. [ABSTRACT FROM AUTHOR]

The Wendelstein 7-X modular advanced stellarator is in the commissioning phase at the Max Planck Institute for Plasma Physics in Greifswald, Germany. The focus of the numerical analysis has been shifted from support of the machine design and assembly toward preparation of the commissioning steps, assessment of possible field disturbances under operational loads, and exploration of operational limits. This paper emphasizes on the development, evolution, and realization of new analysis strategies, as well as on implemented numerical approaches for electromagnetic, thermal, and structural analyses. Remarkable results of the first comparisons with measurements from the extended mechanical instrumentation system are presented in detail and cover evacuation/flooding of the cryostat and plasma vessel, the first cooldown of the magnet system (MS), and both the superconducting coil groups and integral MS commissioning. Finally, some lessons learned during the transition phase are highlighted, which might be relevant for other large fusion machines. [ABSTRACT FROM AUTHOR]

Objectives: Antiretroviral combination therapy of patients infected with HIV has greatly increased their life expectancy. Hence, the treatment of HIV-related long-term complications and age-related comorbidities has become more important. Reported incidence rates of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH) are increasing in HIV-positive patients, potentially requiring treatment with phosphodiesterase 5 inhibitors such as sildenafil or tadalafil. In vitro, the NNRTI rilpivirine is both a pregnane X receptor agonist and cytochrome P450 (CYP) 3A inhibitor. Clinical data concerning the potential effects of rilpivirine coadministration on the pharmacokinetics of the CYP3A substrate tadalafil are lacking.Methods: We enrolled 20 healthy volunteers in an open-label, two-part, one-arm Phase I clinical trial to investigate acute and chronic effects of multiple doses of 25 mg of oral rilpivirine on single-dose and steady-state pharmacokinetics of multiple oral 20 mg doses of tadalafil. CYP3A activity was measured simultaneously with the oral midazolam microdose test.Results: We did not observe a change of tadalafil single-dose and steady-state exposure or of CYP3A activity measured at initiation, during maintenance and upon discontinuation of rilpivirine treatment after single-dose and chronic administration of rilpivirine.Conclusions: Tadalafil can be combined with rilpivirine without dose adjustment or drug monitoring in HIV patients with ED or PAH. Rilpivirine at daily therapeutic doses of 25 mg does not induce or inhibit CYP3A-dependent drug metabolism. [ABSTRACT FROM AUTHOR]

Polynuclear aromatic hydrocarbons (PAHs) from oil were present in some shrimp from Port Valdez, site of a ballast water treatment facility at the Alyeska Alaska Marine Terminal (AMT). Low-level petrogenic PAH concentrations were generally restricted to shrimp eggs in the vicinity of the AMT and extended along the southern shore of Port Valdez to Anderson Bay. Eggs had greater lipid content than other tissues and thus were the most vulnerable biological compartment to hydrocarbon accumulation. Petrogenic hydrocarbons were not observed in shrimp muscle and cephalothoraxes; thus, these tissues do not pose a human health risk. Risk for children older than age 2 years and adults consuming eggs also was low except for two unusual samples (of 32), collected about 17 km west of the treatment facility. In general, PAH loads were consistent with local time series data in other species. We infer that the accumulation mechanism was dissolved uptake from water, consistent with passive sampler observations completed more than a decade earlier. Hydrocarbon levels in the majority of samples were below toxic thresholds. Total PAH accumulation was substantially greater in some pink shrimp than in other species, thus differences in habitat utilization (muddy vs. rocky substrate) are potentially important. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy of para-aneurysmal saline injection for closure of postcatheterization pseudo-aneurysm (PA) at the vascular access site. Methods: Fifty-one consecutive patients with postcatheterization PA at the vascular access site were included to undergo percutaneous para-aneurysmal saline injection. In case of technical failure the day after, PA were treated by bovine thrombin injection. Anatomical properties of the PA were recorded as were details to injection. Results: Initially all patients exhibited success which was reduced to 43 % at day one. A saline volume of median 7 ml (interquartile range 6-8 ml) has been injected. The amount of injected saline was not different in patients with and without treatment success at day one ( P = 0.6). Several anatomical properties of the PA exhibited marked differences in patients with or without success. The length (10.3 mm (7.8-12.0) vs. 12.5 mm (10.3-15.0); P = 0.009) and the angulation (110° (100-118) vs. 140° (129-146); P < 0.001) of the fistula/vessel axis was statistically different between groups. The peak systolic velocity failed to show significance with a tendency to higher values in the ineffective study group ( P = 0.07). No peripheral complications occurred. Conclusion: Para-aneurysmal saline injection may be a therapeutic alternative to percutaneous thrombin injection in patients exhibiting favorable anatomical properties. [ABSTRACT FROM AUTHOR]