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Short-term intake of selective serotonin reuptake inhibitors (SSRIs) modulates threat-related amygdala responses in healthy individuals. However, how SSRI intake over a clinically relevant time period modulates threat-related amygdala responses is less clear. In a semi-randomised, double-blind, placebo-controlled study of 64 healthy individuals (SSRI n = 32, placebo n = 32), we examined the effect of 3–5 weeks of SSRI escitalopram (20 mg daily) on brain response to angry, fearful and neutral faces using BOLD fMRI. Data was analysed using a whole-brain region-wise approach extracting standardised effects (i.e., Cohen’s D). The study was conducted at the Copenhagen University Hospital. A priori, we hypothesised that SSRI would attenuate amygdala responses to angry and fearful faces but not to neutral ones. Whether SSRI modulates correlations between amygdala responses to emotional faces and negative mood states was also explored. Compared to placebo, 3–5 weeks of SSRI intake did not significantly affect the amygdala response to angry, fearful, or neutral faces (|Cohen’s D|< 0.2, PFWER = 1). Whole-brain, region-wise analyses revealed significant differences in frontal (|Cohen’s D|< 0.6, PFWER <.01) and occipital regions (|Cohen’s D|< 0.5, PFWER <.01). SSRI did not modulate correlations between amygdala responses to emotional faces and negative mood states. Our findings indicate that a 3–5 week SSRI intake impacts cortical responses to emotional stimuli, an effect possibly involved in SSRI’s therapeutic efficacy. Trial registration Clinical Trials NCT04239339. [ABSTRACT FROM AUTHOR]

We synthesized six samples in the compositional field NaMgAl(SO4)3–KMgAl(SO4)3 in 20 mol% increments from pure Na to pure K compounds. We investigated them by Powder X-Ray diffraction, 23Na, and 27Al Nuclear Magnetic Resonance spectroscopy. The results confirm NaMgAl(SO4)3 as a unique phase identical to a presumed new mineral found in the fumaroles of Eldfell and Hekla volcanoes in Iceland. It tolerates less than 10 mol% K substitution for Na. There exists a compositional gap to approximately Na0.65K0.35MgAl(SO4)3 from where a solid solution extends to KMgAl(SO4)3. The mineral koryakite [NaKMg2Al2(SO4)6] is a member of the latter solid solution series. The crystal structures of all (Na,K)MgAl(SO4)3 phases are akin to NASICON (NA Super Ionic CONductor). NaMgAl(SO4)3 has R 3 ¯ c symmetry and a disordered distribution of Mg and Al among the octahedral sites with only one unique site for the alkali atom. The members of the solid solution have R 3 ¯ symmetry with ordered Mg–Al distribution and two unique alkali sites with different preferences for Na and K. In the crystal structure, the coordination of Na and/or K is trigonal antiprismatic, and these share bases with two octahedral Mg (Na) or Al (K) coordinations. These polyhedra are arranged in columns parallel to [001] and interconnected by SO4 tetrahedral groups. The alkali atoms from a column lie in the same (001) layers as the octahedrally coordinated atoms from the three neighboring rows. On the same level, parallel to (001), there are gaps in the other three neighboring columns forming channels containing Na+ or K+ ions. [ABSTRACT FROM AUTHOR]

This article presents a discussion inspired by the invitation formed by Kevin Carriere's book: "Psychology in Policy – Redefining Politics Through The Individual". From a theoretical standpoint in culture psychology Carriere challenges the idea of politics as a particular practice carried out by mainly politicians. Instead, he attempts to anchor processes of politics in the everyday lives of individuals, directed at changing their worlds. In this article, we discuss how this ambition could evolve even further by relating it to other theoretical approaches working with similar ambitions. [ABSTRACT FROM AUTHOR]

We explore the role of elites for development and the spread of industrialized dairying in Denmark in the 1880s. We demonstrate that the location of early proto-modern dairies, introduced by landowning elites from northern Germany in the eighteenth century, explains the location of industrialized dairying in 1890: an increase of one standard deviation in elite influence increases industrialized dairying by 56 percent of the mean exposure in one specification. We interpret this as evidence for a spread of ideas from the elites to the peasantry, which we capture through measures of specialization in dairying and demand for education and identify a causal relationship using an instrument based on distance to the influential first mover. Finally, we demonstrate that areas with cooperatives enjoyed greater wealth by the twentieth century, and that they are today associated with other Danish cultural attributes: a belief in democracy and individualism. [ABSTRACT FROM AUTHOR]

We synthesized six samples in the compositional field NaMgAl(SO4)3–KMgAl(SO4)3 in 20 mol% increments from pure Na to pure K compounds. We investigated them by Powder X-Ray diffraction, 23Na, and 27Al Nuclear Magnetic Resonance spectroscopy. The results confirm NaMgAl(SO4)3 as a unique phase identical to a presumed new mineral found in the fumaroles of Eldfell and Hekla volcanoes in Iceland. It tolerates less than 10 mol% K substitution for Na. There exists a compositional gap to approximately Na0.65K0.35MgAl(SO4)3 from where a solid solution extends to KMgAl(SO4)3. The mineral koryakite [NaKMg2Al2(SO4)6] is a member of the latter solid solution series. The crystal structures of all (Na,K)MgAl(SO4)3 phases are akin to NASICON (NA Super Ionic CONductor). NaMgAl(SO4)3 has R 3 ¯ c symmetry and a disordered distribution of Mg and Al among the octahedral sites with only one unique site for the alkali atom. The members of the solid solution have R 3 ¯ symmetry with ordered Mg–Al distribution and two unique alkali sites with different preferences for Na and K. In the crystal structure, the coordination of Na and/or K is trigonal antiprismatic, and these share bases with two octahedral Mg (Na) or Al (K) coordinations. These polyhedra are arranged in columns parallel to [001] and interconnected by SO4 tetrahedral groups. The alkali atoms from a column lie in the same (001) layers as the octahedrally coordinated atoms from the three neighboring rows. On the same level, parallel to (001), there are gaps in the other three neighboring columns forming channels containing Na+ or K+ ions. [ABSTRACT FROM AUTHOR]

The serotonin transporter (5-HTT) critically shapes serotonin neurotransmission by regulating extracellular brain serotonin levels; it remains unclear to what extent 5-HTT levels in the human brain are genetically determined. Here we applied [11C]DASB positron emission tomography to image brain 5-HTT levels and evaluated associations with five common serotonin-related genetic variants that might indirectly regulate 5-HTT levels (BDNF rs6265, SLC6A4 5-HTTLPR, HTR1A rs6295, HTR2A rs7333412, and MAOA rs1137070) in 140 healthy volunteers. In addition, we explored whether these variants could predict in vivo 5-HTT levels using a five-fold cross-validation random forest framework. MAOA rs1137070 T-carriers showed significantly higher brain 5-HTT levels compared to C-homozygotes (2–11% across caudate, putamen, midbrain, thalamus, hippocampus, amygdala and neocortex). We did not observe significant associations for the HTR1A rs6295 and HTR2A rs7333412 genotypes. Our previously observed lower subcortical 5-HTT availability for rs6265 met-carriers remained in the presence of these additional variants. Despite this significant association, our prediction models showed that genotype moderately improved prediction of 5-HTT in caudate, but effects were not statistically significant after adjustment for multiple comparisons. Our observations provide additional evidence that serotonin-related genetic variants modulate adult human brain serotonin neurotransmission. [ABSTRACT FROM AUTHOR]

Background: Currently, bariatric surgery is the most effective long-term treatment of obesity. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the primary types of bariatric surgery performed worldwide. To minimize the risks of surgical complications and optimize cost-effectiveness, it is essential to develop fast-track protocols and patient logistics. At Aleris Hospitals in Denmark, a fast-track methodology in bariatric surgery has been implemented and continuously optimized over the last 15 years. The main objective was to demonstrate timelines recorded during one consecutive year in a fast-track, high-volume bariatric surgery setting after logistic optimization. Methods: This study included 949 consecutive patients who had undergone primary bariatric surgery in 2021. The primary outcomes were length of hospital stay and perioperative timeline recordings that were prospectively collected. The secondary outcomes were mortality, complication rates, and weight loss data. Results: The vast majority of our patients (99.1%) were discharged from the hospital within the day after surgery. The median total surgery time was 30 min, after 12 min of patient preparation and with a turnover time between patients of seven min. The median knife-to-knife time in one operating room was 56 min. Mortality was zero, 30-day reoperation rate was 1.2%, and 30-day readmission rate was 0.8%. SG and RYGB patients had an excess weight loss after four months of 45.6% and 57.9%, respectively. Conclusion: Implementation of fast-track principles in the clinical practice of bariatric surgery allows for an optimized, cost-effective surgical organization supporting the quality of procedures and patient safety. [ABSTRACT FROM AUTHOR]

Purpose : Complication rates after fast-track optimization in bariatric surgery are varying. The aim of this study was to identify short-term complications in patients undergoing laparoscopic sleeve gastrectomy (SG) in an ERABS (enhanced recovery after bariatric surgery) optimized setup. Materials and Methods: This study is an observational analysis of a consecutive cohort of 1600 patients undergoing SG at an ERABS-optimized, private hospital during 2020 and 2021. Primary outcomes were length of stay, mortality, readmissions, reoperations, and complications according to the Clavien-Dindo classification (CDC) within postoperative day (POD) 30 and 90. Secondary outcomes were weight loss and quality of life (QoL) according to Moorehead-Ardelt questionnaires during the first postoperative year. Results: Primary outcomes: 99.1% of patients were discharged within POD 1. The 90-day mortality rate was zero. There were 1% readmissions and 1.2% reoperations within POD 30. Total 30-day complication rate was 4.6%, where 3.4% accounted for CDC grades ≤ II, and 1.3% accounted for CDC grade III. There were zero grade IV–V complications. Secondary outcomes: One year after surgery, weight loss was substantial (p < 0.001), with an excess weight loss of 71.9%, and QoL had significantly increased (p < 0.001). Conclusion: This study demonstrates that the use of an ERABS protocol in bariatric surgery does not compromise neither safety nor efficacy. Complication rates were low, and weight loss was significant. This study thus provides strong arguments that ERABS programs are beneficial in bariatric surgery. [ABSTRACT FROM AUTHOR]

This study investigates the influence of wood pellet properties on the grindability of pellets in a lab-scale disc mill. The pellet properties investigated included wood type, moisture content, internal pellet particle size distribution, particle density, and durability. Two pellet qualities for industrial use (designated I1 and I2 as per ISO 17225-2:2014) and two types of semi-industrial pellets (beech and pine) were used and grinding was performed on as-received and oven-dried pellets. The grinding performance was assessed by measuring the grinding energy and analyzing the changes in particle morphology (size and shape) with respect to the internal pellet particle morphology. Von Rittinger's comminution law was used to characterize the pellet grindability. Drying pellets increased their brittleness and improved their grindability, resulting in both grinding energy savings and a higher milled product fineness, and the impact of drying was larger for industrial pellets. Beech pellets had a better grindability (kWh mm t-1 dry wood) than pine pellets (kWh mm t-1 dry wood). The moisture content of pellets did not influence the shape of the milled particles in terms of circularity and elongation ratio. The study also showed that the proposed disc mill has the potential to quickly determine the relative grindability characteristics of various pellet qualities. [ABSTRACT FROM AUTHOR]

We analyze the link between "too big to fail" (TBTF) and moral hazard using a natural experiment from an epoch of unregulated commercial banking in Denmark. In 1908 the country faced a large banking shock where the creditors of distressed commercial banks received a bailout by the government for the first time in Danish history. Due to a fortuitous combination of circumstances, banks continued to operate in an unregulated environment for more than a decade after the bailout. By considering a sample from a pre-regulation epoch, we isolate the TBTF effect. Our empirical analysis shows that TBTF banks significantly reduced post-bailout capital ratios compared to other banks. [ABSTRACT FROM AUTHOR]

Objective: Magnetic resonance imaging (MRI)-based techniques for non-invasive assessing liver iron concentration (LIC) in patients with iron overload have a limited upper measuring range around 35 mg/g dry weight, caused by signal loss from accelerated T1-, T2-, T2* shortening with increasing LIC. Expansion of this range is necessary to allow evaluation of patients with very high LIC. Aim: To assess measuring range of a gradient-echo R2* method and a T1-weighted spin-echo (SE), signal intensity ratio (SIR)-based method (TE = 25 ms, TR = 560 ms), and to extend the upper measuring range of the SIR method by optimizing echo time (TE) and repetition time (TR) in iron-loaded minipigs. Methods: Thirteen mini pigs were followed up during dextran-iron loading with repeated percutaneous liver biopsies for chemical LIC measurement and MRIs for parallel non-invasive estimation of LIC (81 examinations) using different TEs and TRs. Results: SIR and R2* method had similar upper measuring range around 34 mg/g and similar method agreement. Using TE = 12 ms and TR = 1200 ms extended the upper measuring range to 115 mg/g and yielded good method of agreement. Discussion: The wider measuring range is likely caused by lesser sensitivity of the SE sequence to iron, due to shorter TE, leading to later signal loss at high LIC, allowing evaluation of most severe hepatic iron overload. Validation in iron-loaded patients is necessary. [ABSTRACT FROM AUTHOR]

Path planning and task scheduling are two challenging problems in the design of multiple autonomous agents. Both problems can be solved by the use of exhaustive search techniques such as model checking and algorithmic game theory. However, model checking suffers from the infamous state-space explosion problem that makes it inefficient at solving the problems when the number of agents is large, which is often the case in realistic scenarios. In this paper, we propose a new version of our novel approach called MCRL that integrates model checking and reinforcement learning to alleviate this scalability limitation. We apply this new technique to synthesize path planning and task scheduling strategies for multiple autonomous agents. Our method is capable of handling a larger number of agents if compared to what is feasibly handled by the model-checking technique alone. Additionally, MCRL also guarantees the correctness of the synthesis results via post-verification. The method is implemented in UPPAAL STRATEGO and leverages our tool MALTA for model generation, such that one can use the method with less effort of model construction and higher efficiency of learning than those of the original MCRL. We demonstrate the feasibility of our approach on an industrial case study: an autonomous quarry, and discuss the strengths and weaknesses of the methods. [ABSTRACT FROM AUTHOR]

This special issue contains six revised and extended versions of tool papers that appeared in the proceedings of TACAS 2021, the 27th International Conference on Tools and Algorithms for the Construction and Analysis of Systems. The issue is dedicated to the realization of algorithms in tools and the studies of the application of these tools for analysing hard- and software systems. [ABSTRACT FROM AUTHOR]

This study collected rectal swabs from diarrheal patients and in-house environmental samples from low-income households in Dhaka City, Bangladesh, over a 4-month period and investigated these to determine the domestic transmission pathways of Escherichia coli-associated diarrhea. The environmental samples included swabs from four frequently touched surfaces, drinking water and food. Both the rectal swabs and environmental samples were examined for virulence genes characteristic of diarrheagenic E. coli pathotypes by PCR. In addition, each sample was cultured for E. coli, and the strains were analyzed for virulence profile and subjected to multilocus sequence typing (MLST). The results showed that 31% (73 of 233) of all samples including rectal swabs and household samples were positive for one or more of the diarrheagenic E. coli virulence factors. PCR analyses showed that 28% (10/36) of the rectal swabs, 43% (58/136) of household swabs, 9% (3/32) of the food, and 7% (2/29) of the water samples were positive for various virulence genes. 6 Out of the 36 rectal swab samples and associated household samples were shown to have similar E. coli pathotypic genes, and the drinking vessel surface was identified as the major source of contamination. EAEC and CTEC were the most commonly identified pathotypes in the cultured isolates. The phylogenetic tree constructed by MLST data showed that the diarrheagenic isolates were clustered in several diversified lineages. This study supports the hypothesis that there are high-risk hotspots, particularly those surfaces associated with food consumption, for diarrheagenic E. coli contamination within the household environments of Bangladesh. [ABSTRACT FROM AUTHOR]

Lactose-free dairy products are in great demand worldwide due to the high prevalence of lactose intolerance. To make lactose-free dairy products, commercially available β-galactosidase enzymes, also termed lactases, are used to break down lactose to its constituent monosaccharides, glucose and galactose. In this mini-review, the characteristics of lactase enzymes, their origin, and ways of use are discussed in light of their potential for hydrolyzing lactose. We also discuss whole-cell lactase catalysts, which appear to have great potential in terms of cost reduction and convenience, and which are more natural alternatives to purified enzymes. Lactic acid bacteria (LAB) already used in food fermentations seem to be optimal candidates for whole-cell lactases. However, they have not been industrially exploited yet due to technical hurdles. For whole-cell lactases to be efficient, the lactase enzymes inside the cells must be made available for lactose hydrolysis, and thus, cells need to be permeabilized or disrupted prior to use. Here we review state-of-the-art approaches for disrupting or permeabilizing microorganisms. Lastly, based on recent scientific achievements, we propose a novel, resource-efficient, and low-cost scenario for achieving lactose hydrolysis at a dairy plant using a LAB whole-cell lactase. Key points • Lactases (β-galactosidase) are essential for producing lactose-free dairy products • Novel permeabilization techniques facilitate the use of LAB lactases • Whole-cell lactase catalysts have great potential for reducing costs and resources [ABSTRACT FROM AUTHOR]

The aim of this study was to examine variations in use of antidepressants among children and adolescents in the three Scandinavian countries (Sweden, Norway, and Denmark). We identified new users of antidepressants (5–17 years) during 2007–2018 and described the annual incidence rate, treatment duration, concomitant psychotropic drug use, and the clinical setting of the prescribing physician (in Sweden and Denmark). Incident use of antidepressants increased by a factor 1.9 in Sweden, 1.3 in Norway and decreased by a factor 0.6 in Denmark during the study period. In Sweden, 58% of antidepressant users were covered by a prescription 12 months after initiation compared to 40% in Norway and 49% in Denmark. Also, 34% of Swedish antidepressant users were in continuous treatment after 12 months compared to 26% in Norway and 31% in Denmark. Concomitant use of other psychotropics was more common in Sweden (57%) than in Norway (37%) and Denmark (27%). During 2007–2018, clinicians from psychiatry settings initiated 75% of antidepressant treatments in Sweden, while this was the case for 50% of prescriptions in Denmark, although the proportion increased over time. The number of new antidepressant users is high and still rising in Sweden compared to Norway and Denmark. Swedish antidepressant users are more likely to use other psychotropics and to be covered by an antidepressant prescription after one year. Most antidepressants in Sweden are prescribed by physicians within psychiatric settings suggesting that they are based on specialized psychiatric evaluation. [ABSTRACT FROM AUTHOR]

The Attack Defense Tree framework was developed to facilitate abstract reasoning about security issues of complex systems. As such, a zoo of techniques and extensions have emerged in an attempt to extend the simple Boolean logic of Attack Defense Trees with behavioral properties and quantities. In this paper we expand the modeling power of Attack Defense Trees by introducing a notion of temporal dependencies between attacks, forcing specific ordering of event in successful attacks. Importantly, we introduce a notion of policy for the defender, facilitating a pseudo-active defender, mechanically reacting to the choices of an attacker. To easen the use of Attack Defense Trees we introduce a domain specific language (DSL) and an accompanying tool. The introduction of the DSL facilitates reuse, modularity, collaborative tree construction and separation of logical properties and quantitative/behavioral elements. The usefulness of our framework is exhibited on a small running example, utilizing the policy-notion to implement a reactive Break The Glass policy. We note that all the implemented analysis techniques use well established tools from the formal methods community to produce the given results, relying on non-trivial and automatic translation to and from the target formalisms. Lastly we present our Open Source prototype-tool, capable of conducting various analysis and visualizing the results. [ABSTRACT FROM AUTHOR]

The ability of bacteria to aggregate and form biofilms impairs phagocytosis by polymorphonuclear leukocytes (PMNs). The aim of this study was to examine if the size of aggregates is critical for successful phagocytosis and how bacterial biofilms evade phagocytosis. We investigated the live interaction between PMNs and Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Staphylococcus epidermidis using confocal scanning laser microscopy. Aggregate size significantly affected phagocytosis outcome and larger aggregates were less likely to be phagocytized. Aggregates of S. epidermidis were also less likely to be phagocytized than equally-sized aggregates of the other three species. We found that only aggregates of approx. 5 μm diameter or smaller were consistently phagocytosed. We demonstrate that planktonic and aggregated cells of all four species significantly reduced the viability of PMNs after 4 h of incubation. Our results indicate that larger bacterial aggregates are less likely to be phagocytosed by PMNs and we propose that, if the aggregates become too large, circulating PMNs may not be able to phagocytose them quickly enough, which may lead to chronic infection. [ABSTRACT FROM AUTHOR]

β-galactosidases, commonly referred to as lactases, are used for producing lactose-free dairy products. Lactases are usually purified from microbial sources, which is a costly process. Here, we explored the potential that lies in using whole cells of a food-grade dairy lactic acid bacterium, Streptococcus thermophilus, as a substitute for purified lactase. We found that S. thermophilus cells, when treated with the antimicrobial peptide nisin, were able to hydrolyze lactose efficiently. The rate of hydrolysis increased with temperature; however, above 50 °C, stability was compromised. Different S. thermophilus strains were tested, and the best candidate was able to hydrolyze 80% of the lactose in a 50 g/L solution in 4 h at 50 °C, using only 0.1 g/L cells (dry weight basis). We demonstrated that it was possible to grow the cell catalyst on dairy waste, and furthermore, that a cell-free supernatant of a culture of a nisin-producing Lactococcus lactis strain could be used instead of purified nisin, which reduced cost of use significantly. Finally, we tested the cell catalysts in milk, where lactose also was efficiently hydrolyzed. The method presented is natural and low-cost, and allows for production of clean-label and lactose-free dairy products without using commercial enzymes from recombinant microorganisms. Key points: • Nisin-permeabilized Streptococcus thermophilus cells can hydrolyze lactose efficiently. • A low-cost and more sustainable alternative to purified lactase enzymes. • Reduction of overall sugar content. • Clean-label production of lactose-free dairy products. [ABSTRACT FROM AUTHOR]

International trade in services is a dominant feature of the global economy but it has not received a corresponding level of attention in international business research. In this study, we review the status of research on the internationalisation of services and service firms in the international business domain in order to derive questions for future research. We replicate and extend Merchant and Gaur's (Management International Review 48, p. 379–396, 2008) review of research on the internationalisation of non-manufacturing firms for the following 10 years (2009–2018) for five leading international business journals. In addition to providing a qualitative content analysis of the literature, we extend the study to all research published by 2018 to identify research gaps and emerging research themes. Overall, we find that while research on service internationalisation has increased, the field remains fragmented and lacks theoretical and conceptual development applicable to the internationalisation of services. This creates opportunities for future research. [ABSTRACT FROM AUTHOR]

Background: Fulvestrant is a selective oestrogen receptor (ER) degrader used as monotherapy and combination therapy for ER positive HER2 negative advanced breast cancer (ABC) in postmenopausal women. The drug response predictor (DRP), is a mathematical algorithm based on the expression of multiple genes in the tumour. The fulvestrant DRP algorithm has previously shown effect in BC. In this study, we investigated the DRP's potential in predicting fulvestrant benefit. Method: Among 695 patients with ABC prospectively included in a Danish Breast Cancer Cooperative Group (DBCG) cohort we retrospectively included 226 patients who received fulvestrant as monotherapy. The DRP result was based on mRNA extracted from tumour biopsies and analysed using Affymetrix array. Primary endpoint was time to progression (TTP). Results: For patients who received fulvestrant in line one to four and were previously unexposed to adjuvant endocrine therapy, we identified a hazard ratio (HR) of 0.44 (90% confidence interval (90% CI) upper limit of 1.08, one sided p = 0.066) for a predicted positive vs negative outcome. A weaker association was seen when including patients exposed to adjuvant endocrine treatment or received fulvestrant in fifth or later lines. Exploratory analyses showed that the DRP was efficient when using recent biopsies for DRP estimate and among recently treated patients. Conclusion: The DRP showed a potential in predicting fulvestrant treatment but was not significant in the overall analysis. Use of older biopsies, long-term endocrine treatment and multiple therapies between biopsy used for analysis and fulvestrant treatment, probably affect the predictive accuracy. [ABSTRACT FROM AUTHOR]

This paper contributes to the debate on the impact of agricultural productivity on long run economic development. It presents evidence that widespread adoption of clover contributed to local economic development based on a panel of 56 Danish market towns. We adopt a differences-in-differences approach augmented by an instrumental variable and find that the adoption of clover accounts for about 8 percent of the growth in market town population from 1672 to 1901. The analysis suggests that the effect of the adoption of clover on the process of development was mediated by its impact on human capital formation. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with physical inactivity and impaired health-related quality of life (HRQoL). We aim to test the hypothesis that Roux-en-Y gastric bypass (RYGB) followed by supervised physical training improves physical activity (PA) levels and HRQoL.Methods: Sixty patients, qualified for RYGB, were at 6 months post-surgery randomized to 26 weeks of a supervised physical training intervention (INT) or to a control (CON) group. PA was assessed by accelerometry and using the questionnaire RPAQ. HRQoL was measured by the SF-36 questionnaire. All assessments were performed pre-surgery and 6, 12, and 24 months post-surgery.Results: RYGB did not improve objectively or self-reported PA, but improved all domains of SF-36 (all p < 0.01). Objectively measured light PA, moderate to vigorous PA, and step counts tended to increase in INT compared to CON 12 months after RYGB (0.05 < p < 0.09), but the effects failed to persist. The SF-36 domain "general health" increased in INT compared to CON 24 months after RYGB (p = 0.041).Conclusion: RYGB improves HRQoL, but does not increase PA. Supervised physical training intervention improves general health 24 months after RYGB and tends to improve certain domains of PA right after the intervention period, but fails to increase the patients' overall PA level over time. Clinical Trial Registration Registered at ClinicalTrials.gov-no. NCT01690728. [ABSTRACT FROM AUTHOR]

To better understand the types and quantity of mental health services and medication usage for youth diagnosed with bipolar disorder (BD) within an integrated healthcare system, medical records were reviewed from 2000 to 2011. Eighty-five youth diagnosed with BD were identified and healthcare services (medication and psychotherapy follow-up appointments, emergency room (ER) visits, admissions, phone contacts) and visit-related details (medication usage) were abstracted for 2 years after initial BD diagnosis. Despite complex medication regimens (91.7 and 81.2 % received mood stabilizers and antipsychotic agents, respectively), medication appointments were infrequent, averaging 1 visit every 2 months. Only 36 (42 %) of 85 youth were noted to receive psychotherapy services following BD diagnosis, also averaging 1 visit every 2 months. Most (58.8 %) patients needed one or more hospitalizations during the follow-up period; nearly half (48.2 %) had psychiatric ER visits. The relative lack of psychotherapy and infrequent follow-up visits suggests need for improvement to optimize healthcare delivery. [ABSTRACT FROM AUTHOR]

Purpose: Anthracyclines remain a cornerstone in the treatment of primary and advanced breast cancer (BC). This study has evaluated the predictive value of a multigene mRNA-based drug response predictor (DRP) in the treatment of advanced BC with epirubicin. The DRP is a mathematical method combining in vitro sensitivity and gene expression with clinical genetic information from > 3000 clinical tumor samples.Methods: From a DBCG cohort, 140 consecutive patients were treated with epirubicin between May 1997 and November 2016. After patient informed consent, mRNA was isolated from archival formalin-fixed paraffin-embedded primary breast tumor tissue and analyzed using Affymetrix arrays. Using time to progression (TTP) as primary endpoint, the efficacy of epirubicin was analyzed according to DRP combined with clinicopathological data collected retrospectively from patients’ medical records. Statistical analysis was done using Cox proportional hazards model stratified by treatment line.Results: Median TTP was 9.3 months. The DRP was significantly associated to TTP (P = 0.03). The hazard ratio for DRP scores differing by 50 percentage points was 0.55 (95% CI -0.93, one-sided). A 75% DRP was associated with a median TTP of 13 months compared to 7 months following a 25% DRP. Multivariate analysis showed that DRP was independent of age and number of metastases.Conclusion: The current study prospectively validates the predictive capability of DRP regarding epirubicin previously shown retrospectively allowing the patients predicted to be poor responders to choose more effective alternatives. Randomized prospective studies are needed to demonstrate if such an approach will lead to increased overall survival. [ABSTRACT FROM AUTHOR]

Automatic strategy synthesis for a given control objective can be used to generate correct-by-construction controllers of real-time reactive systems. The existing symbolic approach for continuous timed game is a computationally hard task and current tools like UPPAAL TiGa often scale poorly with the model complexity. We suggest an explicit approach for strategy synthesis in the discrete-time setting and show that even for systems with closed guards, the existence of a safety discrete-time strategy does not imply the existence of a safety continuous-time strategy and vice versa. Nevertheless, we prove that the answers to the existence of discrete-time and continuous-time safety strategies coincide on a practically motivated subclass of urgent controllers that either react immediately after receiving an environmental input or wait with the decision until a next event is triggered by the environment. We then develop an on-the-fly synthesis algorithm for discrete timed-arc Petri net games. The algorithm is implemented in our tool TAPAAL, and based on the experimental evidence, we discuss the advantages of our approach compared to the symbolic continuous-time techniques. [ABSTRACT FROM AUTHOR]

Fine-tuning the expression level of multiple genes is usually pivotal for metabolic optimization. We have developed a tool for this purpose for the important industrial workhorse Corynebacterium glutamicum that allows for the introduction of synthetic promoter-driven expression libraries of arbitrary genes. We first devised a method for introducing genetic elements into the chromosome repeatedly, relying on site-specific recombinases and the vector pJS31 serving as the carrier. The pJS31 vector contains a synthetic cassette including a phage attachment site attP for integration, a bacterial attachment site attB for subsequent integration, a multiple cloning site, and two modified loxP sites to facilitate easy removal of undesirable vector elements. Meanwhile, we constructed a derivative of the wild-type strain ATCC 13032 carrying an attB site in its chromosome (JS34) and demonstrated that pJS31 readily could integrate into the attB site in this strain providing expression of the corresponding integrase. Subsequent expression of the Cre recombinase promoted recombination between the modified loxP sites, resulting in a strain only retaining the target insertions and an attB site. To simplify the procedure, non-replicating circular expression units for the phage integrase and the Cre recombinase were used. As a showcase, we used the tool to construct a battery of strains simultaneously expressing the two reporter genes, lacZ (encoding β-galactosidase) and gusA (encoding β-glucuronidase), to arbitrary levels. In principle, an unlimited number of genes, whether native, heterologous, or synthetic, can be introduced using the developed approach, and this should greatly facilitate metabolic optimization of this important platform organism. [ABSTRACT FROM AUTHOR]

Understanding socioeconomic inequalities in health care is critical for achieving health equity. The aim of this paper is threefold: 1) to quantify inequality in diabetes health care service utilization; 2) to understand determinants of these inequalities in relation to socio-demographic and clinical morbidity factors; and 3) to compare the empirical outcome of using income level and educational level as proxies for Socio Economic Status (SES). Data on the entire Danish population of diabetes patients in 2011 ( N = 318,729) were applied. Patients' unique personal identification number enabled individual patient data from several national registers to be linked. A concentration index approach with decomposition into contributing factors was applied. Differences in diabetes patients' health care utilization patterns suggest that use of services differ among patients of lower and higher SES, despite the Danish universal health care system. Especially, out-patient services, rehabilitation and specialists in primary care show different utilization patterns according to SES. Comparison of the empirical outcome from using educational level and income level as proxy for patients' SES indicate important differences in inequality estimates. While income, alike other measures of labor market attachment, to a certain extent is explained by morbidity and thus endogenous, education is more decisive for patients' ability to take advantage of the more specialized services provided in a universal health care system. [ABSTRACT FROM AUTHOR]

Possible mediators of the relation between maternal depressive symptomatology and parenting behavior were examined for 96 children with ADHD and their mothers drawn from the Multimodal Treatment Study of Children with ADHD (MTA) as part of an add-on investigation conducted by two of the six MTA sites. General cognitions (i.e., maternal locus of control and self-esteem) and parenting-specific factors (i.e., maternal parenting efficacy and parenting stress) were examined as possible mediators. Findings provide initial support that maternal parenting stress, as well as maternal locus of control and self-esteem mediate the relation between maternal depressive symptomatology and parenting behavior. This provides support for the argument that some families of children with ADHD may benefit from an expanded version of parent management training that includes sessions directly targeting affective and cognitive factors in parents, similar to treatment programs used to treat childhood conduct problems. [ABSTRACT FROM AUTHOR]

Having a sufficient supply of energy, usually in the form of ATP, is essential for all living organisms. In this study, however, we demonstrate that it can be beneficial to reduce ATP availability when the objective is microbial production. By introducing the ATP hydrolyzing F-ATPase into a Lactococcus lactis strain engineered into producing acetoin, we show that production titer and yield both can be increased. At high F-ATPase expression level, the acetoin production yield could be increased by 10 %; however, because of the negative effect that the F-ATPase had on biomass yield and growth, this increase was at the cost of volumetric productivity. By lowering the expression level of the F-ATPase, both the volumetric productivity and the final yield could be increased by 5 % compared to the reference strain not overexpressing the F-ATPase, and in batch fermentation, it was possible to convert 176 mM (32 g/L) of glucose into 146.5 mM (12.9 g/L) acetoin with a yield of 83 % of the theoretical maximum. To further demonstrate the potential of the cell factory developed, we complemented it with the lactose plasmid pLP712, which allowed for growth and acetoin production from a dairy waste stream, deproteinized whey. Using this cheap and renewable feedstock, efficient acetoin production with a titer of 157 mM (14 g/L) acetoin was accomplished. [ABSTRACT FROM AUTHOR]

It is well established that the contamination sources of cholera causing bacteria, Vibrio cholerae, are water and food, but little is known about the transmission role of the fomites (surfaces that can carry pathogens) commonly used in households. In the absence of appropriate nutrients or growth conditions on fomites, bacteria have been known to assume a viable but non-culturable (VBNC) state after a given period of time. To investigate whether and when V. cholerae O1 assumes such a state, this study investigated the survival and viable quantification on a range of fomites such as paper, wood, glass, plastic, cloth and several types of metals under laboratory conditions. The fomites were inoculated with an outbreak strain of V. cholerae and its culturability was examined by drop plate count method at 30 min intervals for up to 6 h. For molecular detection, the viable/dead stain ethidium monoazide (EMA) which inhibits amplification of DNA from dead cells was used in combination with real-time polymerase chain reaction (EMA-qPCR) for direct quantitative analyses of viable V. cholerae at 2, 4, 6, 24 h and 7 day time intervals. Results showed that V. cholerae on glass and aluminum surfaces lost culturability within one hour after inoculation but remained culturable on cloth and wood for up to four hours. VBNC V. cholerae on dry fomite surfaces was detected and quantified by EMA-qPCR even 7 days after inoculation. In conclusion, the prolonged survival of V. cholerae on various household fomites may play vital role in cholera transmission and needs to be further investigated. [ABSTRACT FROM AUTHOR]

This research proposes the hypothesis that societies with long histories of agriculture have less equality in gender roles as a consequence of more patriarchal values and beliefs regarding the proper role of women in society. We test this hypothesis in a world sample of countries, in a sample of European regions, as well as among immigrants and children of immigrants living in the US. This evidence reveals a significant negative relationship between years of agriculture and female labor force participation rates, as well as other measures of equality in contemporary gender roles. This finding is robust to the inclusion of an extensive set of possible confounders, including historical plough-use and the length of the growing season. We argue that two mechanisms can explain the result: (1) societies with longer agricultural histories had a higher level of technological advancement which in the Malthusian Epoch translated into higher fertility and a diminished role for women outside the home; (2) the transition to cereal agriculture led to a division of labor in which women spend more time on processing cereals rather than working in the field. [ABSTRACT FROM AUTHOR]

Background: The objective of the present study was to evaluate the cost-utility of bariatric surgery in a lifetime horizon from a Swedish health care payer perspective. Methods: A decision analytic model using the Markov process was developed covering cardiovascular diseases, type 2 diabetes, and surgical complications. Clinical effectiveness and safety were based on the literature and data from the Scandinavian Obesity Surgery Registry. Gastric bypass, sleeve gastrectomy, and gastric banding were included in the analysis. Cost data were obtained from Swedish sources. Results: Bariatric surgery was cost saving in comparison with conservative management. It also led to a substantial reduction in lifetime risk of events: from a 16 % reduction in the risk of transient ischaemic attacks to a 62 % reduction in the incidence of type 2 diabetes. Over a lifetime, surgery led to savings of €8408 and generated an additional 0.8 years of life and 4.1 quality-adjusted life years (QALYs) per patient, which translates into gains of 32,390 quality-adjusted person-years and savings of €66 million for the cohort, operated in 2012. Analysis of the consequences of a 3-year delay in surgery provision showed that the overall lifetime cost of treatment may be increased in patients with diabetes or a body mass index >40 kg/m. Delays in surgery may also lead to a loss of clinical benefits: up to 0.6 life years and 1.2 QALYs per patient over a lifetime. Conclusion: Bariatric surgery, over a lifetime horizon, may lead to significant cost savings to health care systems in addition to the known clinical benefits. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate the current utilization, the level of endorsement by professional societies, and health technology assessment bodies, as well as the reimbursement levels for bariatric surgery in European countries. Materials and Methods: We performed an analysis of the indications for bariatric surgery based on national clinical and commissioning guidelines, current utilization of surgery, characteristics of patients who underwent surgery, and reimbursement tariffs in Belgium, Denmark, England, France, Germany, Italy, and Sweden. Data were obtained from national patient registries, administrative databases, and published literature for the year 2012. Results: Despite clear consensus outlined in clinical guidelines, significant differences were found in the eligibility criteria for surgery. Patients with no significant comorbidities were deemed eligible if they had a body mass index (BMI) of 40 or 50 kg/m in Denmark. Irrespective of the country, patients with comorbidities were eligible if they had a BMI of 35 kg/m. The highest utilization of bariatric surgery (number of surgeries per 1 M population) was observed in Belgium (928), Sweden (761), and France (571) while Italy (128), England (117), and Germany (72) had the lowest utilization. There was a strong negative correlation between utilization and average BMI level of the patient population ( r = −.909, p = 0.005). The annual per capita spending on surgery differed significantly between countries, ranging from €0.54 in Germany to €4.33 in Belgium. Conclusions: There are significant variations in the clinical indications, utilization, and funding of bariatric surgery in European countries. [ABSTRACT FROM AUTHOR]

Background: The approach to repair of paraesophageal hernias (PEHs) is controversial. Recent data suggest that mesh repair leads to recurrence rates similar to non-mesh approaches, while subjecting patients to mesh-associated complications. Routine fundoplication during PEH repair has been favored despite significant dysphagia rates. We present our multicenter prospective data on laparoscopic PEH repairs using a modified Boerema anterior gastropexy without fundoplication. Methods: We prospectively followed patients after modified Boerema PEH repair at three institutions. Patient demographics, perioperative data, and postoperative outcomes were evaluated. Subjective and objective outcomes were assessed via clinical assessment, follow-up questioning, endoscopy, and radiographic swallow studies. Results: A total of 101 patients were followed a mean of 10.8 (median, 12) months. We encountered 9 (8.9 %) intraoperative complications and 13 (12.9 %) postoperative complications. There was no mortality. Reflux symptoms were absent in 71 patients (70.3 %) postoperatively. Of the remaining subjects, 8 (7.9 %) had mild intermittent reflux without the need for proton pump inhibitors (PPI), 12 (11.9 %) had moderate reflux necessitating PPI as needed, and 10 (9.9 %) had reflux requiring daily PPI. Our recurrence rate, assessed at postoperative endoscopy/barium swallow, was 16.8 %. Of these, 10 (9.9 %) were small segmental recurrences and 7 (6.9 %) were large recurrences. Conclusion: Herein, we demonstrate a favorable recurrence rate while avoiding the potential major complications associated with mesh hiatoplasty. Our data tend to support a tailored approach to incorporation of fundoplication during PEH repair. Postoperative acid reflux was absent in most of our patients, and pharmacotherapy alone was sufficient for those experiencing reflux symptoms. [ABSTRACT FROM AUTHOR]

The current study presents the implementation of a set of school based interventions in a greater New Orleans school district one year following Hurricane Katrina. The interventions included adaptation and implementation of evidence based treatments in a crisis situation with at-risk youth which involved training and clinical challenges. 386 students found to have significant depressive and/or disruptive disorder symptoms received treatment from the School Therapeutic Enhancement Program (STEP). Further, a district-wide mental health needs assessment of middle and high school students (N = 11,861) screened for behavioral and emotional difficulties at the beginning and end of the school year provided a benchmark for community youth's emotional and behavioral distress. High-need intervention students demonstrated clinically significant lower levels of emotional and behavioral problems, depression and inattention in comparison to pre-treatment levels as indicated by multiple informants (i.e., self, parent, teacher). Self-reported distress levels were also lower than screening group students at post-test. These findings support the efficacy of a school-based intervention for youth struggling with the aftereffects of a highly disruptive natural disaster. Implications for utilizing a flexible adaptation of an evidence-based training model involving coaching and consultation are discussed. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis. Methods: Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox regression with time-dependent covariates and joint modelling techniques. Results: Of 267 eligible patients, we analysed 260 patients with TEG data. At 90 days, 68 (26 %) had bled and 139 (53 %) had died. For all TEG variables, hypocoagulability according to the reference range was significantly associated with increased risk of death. In a linear model, hazard ratios for death were 6.03 (95 % confidence interval, 1.64-22.17) for increased clot formation speed, 1.10 (1.04-1.16) for decreased angle, 1.09 (1.05-1.14) for decreased clot strength and 1.12 (1.06-1.18) for decreased fibrinogen contribution to clot strength (functional fibrinogen MA), showing that deterioration towards hypocoagulability in any TEG variable significantly increased the risk of death. Patients treated with HES had lower functional fibrinogen MA than those treated Ringer's acetate, which significantly increased the risk of subsequent bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial. Conclusions: In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding. [ABSTRACT FROM AUTHOR]

This study examines the prevalence and characteristics of services reported by school staff for 543 high school students participating in the 8-year follow-up of the multi-site Multimodal Treatment study of ADHD (MTA). Overall, 51.6 % of students with a history of attention-deficit/hyperactivity disorder (ADHD) were receiving services through an individualized educational plan (IEP) or a 504 plan, a rate higher than expected for this age group. Less than 5 % of these had 504 plans; 35.5 % attended special education classes. Very few services (except tutoring) were provided outside of an IEP or 504 plan. Almost all students with services received some type of academic intervention, whereas only half received any behavioral support or learning strategy. Less than one-fourth of interventions appear to be evidence based. Students receiving services showed greater academic and behavioral needs than those not receiving services. Services varied based upon type of school, with the greatest number of interventions provided to students attending schools that only serve those with disabilities. Original MTA treatment randomization was unrelated to services, but cumulative stimulant medication and greater severity predicted more service receipt. Results highlight a need for accommodations with greater evidence of efficacy and for increased services for students who develop academic difficulties in high school. [ABSTRACT FROM AUTHOR]