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The focus of this study was to learn from the operational variabilities in offshore wind projects by investigating the overall delays in offshore wind projects related to arrival time (flow) or job time (process-time) variability. This research was motivated by the general understanding that flow variability is dominant within the offshore wind domain. The case study presented is based on 183,197 historical data-points from six different cases, the selection of cases was based on overall controllable project features. The findings reveal that from a variability perspective onshore performs better than offshore. The distribution also reveals that the process-time variability is dominant for both the onshore and offshore assembly location. This indicates that the offshore wind project variabilities are controllable and oppose the general understanding within the body of knowledge, however, further research would be required to understand the probable causations. The analysis and its results can be used for later predictions of project schedule outcomes or as explicit external knowledge for comparison. The results of this research project are relevant to both academics and practitioners, not only in offshore wind projects, but also onshore wind and other operations handling remote assembly locations.

Maternal immune activation (MIA) during pregnancy is implicated in offspring psychiatric disorders. However, it is unknown to what extent MIA affects neurodevelopment, particularly cerebrocortical anatomy, in the general population, and whether effects differ by sex. The current study used vertex-wise statistics to examine the association between maternal prenatal CRP, an archetypal systemic inflammatory marker, and offspring cortical thickness, surface area, and volume, in 2635 mother-child dyads (5.4-26.5 years) from three population-based cohorts, and one clinical cohort enriched for presence of inflammation markers. Maternal CRP within a normal physiological range (<10 mg/L) exhibited sex-specific quadratic associations with cortical morphological measures in 2 regions in males and 1 region in females at childhood. Elevated (>10 mg/L) CRP was associated with regional cortical morphology in females and in a pooled sample of sexes. Overall, MIA is associated with cortical development in a regional and sex-specific manner in studies spanning childhood to adulthood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Expecting mothers with high sense of coherence (SOC) exhibit improved physical, emotional, and childbearing health. However, the dimensions of SOC and the factor structure of the SOC-13 scale during prenatal period is slightly known. Especially the differences in experiencing SOC and its components (comprehensibility, manageability, meaningfulness) among both expecting parents (mothers and fathers) is poorly understood. The association between SOC and mood disorder symptoms (depression and anxiety) during pregnancy is scarcely studied., Methods: The structure of the SOC-13 scale, differences in SOC experiences, and the associations between SOC and depressive and anxiety symptoms were studied in a sample of 2784 pregnant women (mothers) and 1661 men/partners (fathers) belonging to the FinnBrain Birth Cohort Study. Self-reports (SOC-13, EPDS, SCL-90: ANX) from gestational week 24 were used. Confirmatory factor analysis (CFA) and invariance testing was carried out to investigate the factorial structure of SOC-13 among both groups (mothers and fathers). Group comparisons were used to study differences in the level of SOC among mothers vs. fathers, low vs. high depression and anxiety subgroups, and multiparous vs. nulliparous mothers., Results: A two-factor model for SOC-13 consisting of comprehensibility-manageability and meaningfulness fitted the data best. Mothers reported higher levels of meaningfulness, whereas fathers reported higher levels of comprehensibility-manageability. SOC was significantly higher among fathers vs. mothers, but mothers with depressive symptoms reported higher SOC than fathers with depressive symptoms., Conclusions: During pregnancy, SOC can be viewed as a two-dimensional (vs. one- or three-dimensional) concept, and mothers and fathers have differences in the components of SOC. Importantly, mothers vs. fathers with depressive symptoms express higher overall SOC indicating that pregnancy may relate to higher than usual SOC especially among women with psychological distress. Understanding how expecting mothers and fathers experience SOC during pregnancy, particularly in relation to depressive symptoms, helps midwives and maternity care providers to focus health promoting support more precisely., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prenatal and postnatal maternal psychological distress predicts various detrimental consequences on social, behavioral, and cognitive development of offspring, especially in girls. Maturation of white matter (WM) continues from prenatal development into adulthood and is thus susceptible to exposures both before and after birth., Methods: WM microstructural features of 130 children (mean age, 5.36 years; range, 5.04-5.79 years; 63 girls) and their association with maternal prenatal and postnatal depressive and anxiety symptoms were investigated with diffusion tensor imaging, tract-based spatial statistics, and regression analyses. Maternal questionnaires were collected during first, second, and third trimesters and at 3, 6, and 12 months postpartum with the Edinburgh Postnatal Depression Scale (EPDS) for depressive symptoms and Symptom Checklist-90 for general anxiety. Covariates included child's sex; child's age; maternal prepregnancy body mass index; maternal age; socioeconomic status; and exposures to smoking, selective serotonin reuptake inhibitors, and synthetic glucocorticoids during pregnancy., Results: Prenatal second-trimester EPDS scores were positively associated with fractional anisotropy in boys (p < .05, 5000 permutations) after controlling for EPDS scores 3 months postpartum. In contrast, postpartum EPDS scores at 3 months correlated negatively with fractional anisotropy (p < .01, 5000 permutations) in widespread areas only in girls after controlling for prenatal second-trimester EPDS scores. Perinatal anxiety was not associated with WM structure., Conclusions: These results suggest that prenatal and postnatal maternal psychological distress is associated with brain WM tract developmental alterations in a sex- and timing-dependent manner. Future studies including behavioral data are required to consolidate associative outcomes for these alterations., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Although instrumental learning deficits are, among other deficits, assumed to contribute to attention-deficit/hyperactivity disorder (ADHD), no comprehensive systematic review of instrumental learning deficits in ADHD exists. This review examines differences between ADHD and typically developing (TD) children in basic instrumental learning and the effects of reinforcement form, magnitude, schedule, and complexity, as well as effects of medication, on instrumental learning in children with ADHD., Method: A systematic search of PubMed, PsyINFO, CINAHL, EMBASE+EMBASE CLASSIC, ERIC, and Web of Science was conducted for articles up to March 16, 2020. Experimental studies comparing instrumental learning between groups (ADHD versus TD) or a manipulation of reinforcement/medication within an ADHD sample were included. Quality of studies was assessed with an adapted version of the Hombrados and Waddington criteria to assess risk of bias in (quasi-) experimental studies., Results: A total of 19 studies from among 3,384 non-duplicate screened articles were included. No difference in basic instrumental learning was found between children with ADHD and TD children, nor effects of form or magnitude of reinforcement. Results regarding reinforcement schedule and reversal learning were mixed, but children with ADHD seemed to show deficits in conditional discrimination learning compared to TD children. Methylphenidate improved instrumental learning in children with ADHD. Quality assessment showed poor quality of studies with respect to sample sizes and outcome and missing data reporting., Conclusion: The review identified very few and highly heterogenous studies, with inconsistent findings. No clear deficit was found in instrumental learning under laboratory conditions. Children with ADHD do show deficits in complex forms of learning, that is, conditional discrimination learning. Clearly more research is needed, using more similar task designs and manipulations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

After 5 months of age, infants begin to prioritize attention to fearful over other facial expressions. One key proposition is that amygdala and related early-maturing subcortical network, is important for emergence of this attentional bias - however, empirical data to support these assertions are lacking. In this prospective longitudinal study, we measured amygdala volumes from MR images in 65 healthy neonates at 2-5 weeks of gestation corrected age and attention disengagement from fearful vs. non-fearful facial expressions at 8 months with eye tracking. Overall, infants were less likely to disengage from fearful than happy/neutral faces, demonstrating an age-typical bias for fear. Left, but not right, amygdala volume (corrected for intracranial volume) was positively associated with the likelihood of disengaging attention from fearful faces to a salient lateral distractor (r = .302, p = .014). No association was observed with the disengagement from neutral or happy faces in equivalent conditions (r = .166 and .125, p = .186 and .320, respectively). These results are the first to link the amygdala volume with the emerging perceptual vigilance for fearful faces during infancy. They suggest a link from the prenatally defined variability in the amygdala size to early postnatal emotional and social traits., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A method for the prediction of the magnetization in flow NMR experiments is presented, which can be applied to mixtures. It enables a quantitative evaluation of NMR spectra of flowing liquid samples even in cases in which the magnetization is limited by the flow. A transport model of the nuclei's magnetization, which is based on the Bloch-equations, is introduced into a computational fluid dynamics (CFD) code. This code predicts the velocity field and relative magnetization of different nuclei for any chosen flow cell geometry, fluid and flow rate. The prediction of relative magnetization is used to correct the observed reduction of signal intensity caused by incomplete premagnetization in fast flowing liquids. By means of the model, quantitative NMR measurements at high flow rates are possible. The method is predictive and enables calculating correction factors for any flow cell design and operating condition based on simple static T 1 time measurements. This makes time-consuming calibration measurements for assessing the influence of flow effects obsolete, which otherwise would have to be carried out for each studied condition. The new method is especially interesting for flow measurements with compact medium field NMR spectrometers, which have small premagnetization volumes. In the present work, experiments with three different flow cells in a medium field NMR spectrometer were carried out. Acetonitrile, water, and mixtures of these components were used as model fluids. The experimental results for the magnetization were compared to the predictions from the CFD model and good agreement was observed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is associated with risk of venous thromboembolism (VTE). It remains unknown whether individual respiratory symptoms and lowered oxygen saturation (SpO 2 ), individually and in combination with COPD, affect the risk of VTE., Objectives: To investigate whether measures of respiratory impairments including respiratory symptoms and SpO 2 , individually and combined with COPD, were associated with an increased risk of VTE., Methods: Spirometry, SpO 2 , and self-reported respiratory symptoms were collected in 8686 participants from the fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study. Incident VTE events were registered from the date of inclusion to December 31, 2016. Cox regression models with exposures and confounders as time-varying covariates (for repeated measurements) were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE., Results: During a median follow-up of 9.1 years, 330 participants developed incident VTE. Subjects with SpO 2  ≤ 96% (lowest 20th percentile) had a 1.5-fold higher risk of VTE (adjusted HR, 1.48; 95% CI, 1.13-1.93) compared with those with SpO 2  ≥ 98%. Severe respiratory symptoms (dyspnea, cough, and phlegm) were associated with a 1.4- to 2.0-fold higher risk of VTE compared with no such symptoms. COPD, combined with respiratory symptoms or lowered SpO 2 , had an additive effect on the VTE risk., Conclusions: Lowered SpO 2 and severe respiratory symptoms were associated with increased VTE risk. COPD combined with respiratory impairments had an additive effect on VTE risk, and may suggest particular attention on VTE preventive strategies in COPD patients with respiratory impairments., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.)

Maternal psychological distress during pregnancy (PPD) 1 has been associated with changes in offspring amygdalar and hippocampal volumes. Studies on child amygdalae suggest that sex moderates the vulnerability of fetal brains to prenatal stress. However, this has not yet been observed in these structures in newborns. Newborn studies are crucial, as they minimize the confounding influence of postnatal life. We investigated the effects of maternal prenatal psychological symptoms on newborn amygdalar and hippocampal volumes and their interactions with newborn sex in 123 newborns aged 2-5 weeks (69 males, 54 females). Based on earlier studies, we anticipated small, but statistically significant effects of PPD on the volumes of these structures. Maternal psychological distress was measured at gestational weeks (GW) 2 14, 24 and 34 using Symptom Checklist-90 (SCL-90, anxiety scale) 3 and Edinburgh Postnatal Depression Scale (EPDS) 4 questionnaires. Newborn sex was found to moderate the relationship between maternal distress symptoms at GW 24 and the volumes of left and right amygdala. This relationship was negative and significant only in males. No significant main effect or sex-based moderation was found for hippocampal volumes. This newborn study provides evidence for a sex-dependent influence of maternal psychiatric symptoms on amygdalar structural development. This association may be relevant to later psychopathology., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: One of the key behavioral phenotypes in infancy are different temperament traits, and certain early life temperament traits have been shown to precede later mental health problems. Differences in the gut microbiota composition (GMC) have been suggested to link with neurodevelopment. For example, toddler temperament traits have been found to associate with differences in GMC; however, studies in infants are lacking although infancy is a rapid period of neurodevelopment as well as GM development. Thus, we aimed to investigate association between infant GMC and temperament., Methods: The study population (n = 301, 53% boys) was drawn from the FinnBrain Birth Cohort Study. Stool samples were collected from the 2.5-month-old infants and sequenced with 16S Illumina MiSeq platform. GMC taxonomic composition (at Genus and OTU level), observed sample clusters, diversity and richness were investigated in relation to the maternal reports of Infant Behavior Questionnaire -Revised (IBQ-R) at the age of 6 months., Results: Three sample clusters (Bifidobacterium/Enterobacteriaceae, Bacteroides, V. Dispar) based on GMC were identified, of which Bifidobacterium/Enterobacteriaceae-cluster presented with higher scores on the IBQ-R main dimension regulation and its subscale duration of orienting compared to Bacteroides-cluster. The clusters associated with temperament in a sex-dependent manner. The IBQ-R main dimension surgency (positive emotionality) was associated positively both with genus Bifidobacterium and Streptococcus. Alpha diversity had a negative association with negative emotionality and fear reactivity., Conclusion: This is the first study demonstrating associations, but not causal connections, between GMC and temperament in young infants in a prospective design., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Physical expressions of affection play a foundational role in early brain development, but the neural correlates of affective touch processing in infancy remain unclear. We examined brain responses to gentle skin stroking, a type of tactile stimulus associated with affectionate touch, in young infants. Thirteen term-born infants aged 11-36days, recruited through the FinnBrain Birth Cohort Study, were included in the study. Soft brush strokes, which activate brain regions linked to somatosensory as well as socio-affective processing in children and adults, were applied to the skin of the right leg during functional magnetic resonance imaging. We examined infant brain responses in two regions-of-interest (ROIs) known to process gentle skin stroking - the postcentral gyrus and posterior insular cortex - and found significant responses in both ROIs. These results suggest that the neonate brain is responsive to gentle skin stroking within the first weeks of age, and that regions linked to primary somatosensory as well as socio-affective processing are activated. Our findings support the notion that social touch may play an important role in early life sensory processing. Future research will elucidate the significance of these findings for human brain development., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Stressors affect populations exposed to them as well as offspring. Strategies preventing the intergenerational propagation of effects of stress would benefit public health. Olfactory cue-based fear conditioning provides a framework to address this issue., Methods: We 1) exposed adult male mice to an odor, acetophenone (Ace) or Lyral (parental generation [F0]-Exposed), 2) trained mice to associate these odors with mild foot shocks (F0-Trained), and 3) trained mice to associate these odors with mild foot shocks and then extinguished their fear toward these odors with odor-only presentations (F0-Extinguished). We then examined sensitivity of future generation (F1) offspring to these odors, expression of M71 odorant (Ace-responsive) and MOR23 odorant (Lyral-responsive) receptor-expressing cell populations in F1 offspring, and DNA methylation at genes encoding the Ace- (Olfr151, Olfr160) and Lyral- (Olfr16) responsive receptors in F0 sperm., Results: Extinguishing fear toward Ace or Lyral of F0 male mice (F0-Extinguished) that had been fear conditioned with Ace or Lyral, respectively, results in F1-Extinguished offspring that do not demonstrate behavioral sensitivity to Ace or Lyral, respectively, and do not have enhanced representation for M71 or MOR23 odorant receptors in the olfactory system, as is observed in F1-Trained-Ace or F1-Trained-Lyral cohorts, respectively. The promoters of genes encoding Olfr151 and Olfr160 receptors are less methylated in F0-Trained-Ace sperm compared with F0-Exposed-Ace sperm. The Olfr16 promoter is less methylated in F0-Trained-Lyral sperm compared with F0-Exposed-Lyral sperm, and F0-Extinguished-Lyral sperm have methylation levels comparable to F0-Exposed-Lyral sperm., Conclusions: Our study demonstrates the potential of using extinction-based behavioral strategies to reverse influences of parental stress in offspring and in the parental germline., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Major depressive disorder constitutes one of the leading causes of disability worldwide. However, it is not a unitary disease-it is a heterogeneous syndrome, with patients differing remarkably in symptom profile, pathophysiology and treatment responsiveness. Previous attempts to subtype major depressive disorder have showed limited clinical applicability. We present a classification of major depressive disorder episodes based on the proximate mechanisms that led to the original mood change that caused the depressive episode. We identify discrete depression subtypes that are induced by: 1) infection, 2) long-term stress, 3) loneliness, 4) traumatic experience, 5) hierarchy conflict, 6) grief, 7) romantic rejection, 8) postpartum events, 9) the season, 10) chemicals, 11) somatic diseases and 12) starvation. We further examine the ultimate functions of these subtypes and show that not all types of mood changes that trigger depression are adaptive. Instead, some are clearly maladaptive and some are byproducts of other adaptations. In modern societies, low mood after adverse life events may turn into a pathological depressive state. Modern lifestyle increases susceptibility to inflammatory dysregulation and chronic stress, both of which increase the amount of proinflammatory cytokines in peripheral blood, leading to low mood and sickness behaviour. Proinflammatory cytokines may aggravate the previously adaptive short-term mood changes to a chronic maladaptive depressive state by preventing the normalization of mood after adverse life events. Subtyping depression enables an effective and intelligent long-term treatment of patients in each subtype by treating the underlying causes of depression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Antigen receptor gene assembly is accomplished in developing lymphocytes by the V(D)J recombination reaction, which can be separated into two steps: DNA cleavage by the recombination-activating gene (RAG) nuclease and joining of DNA double strand breaks (DSBs) by components of the nonhomologous end joining (NHEJ) pathway. Deficiencies for NHEJ factors can result in immunodeficiency and a propensity to accumulate genomic instability, thus highlighting the importance of identifying all players in this process and deciphering their functions. Bcl2 transgenic v-Abl kinase-transformed pro-B cells provide a pseudo-physiological cellular system to study V(D)J recombination. Treatment of v-Abl/Bcl2 pro-B cells with the Abl kinase inhibitor Imatinib leads to G1 cell cycle arrest, the rapid induction of Rag1/2 gene expression and V(D)J recombination. In this system, the Bcl2 transgene alleviates Imatinib-induced apoptosis enabling the analysis of induced V(D)J recombination. Although powerful, the use of mouse models carrying the Bcl2 transgene for the generation of v-Abl pro-B cell lines is time and money consuming. Here, we describe a method for generating v-Abl/Bcl2 pro-B cell lines from wild type mice and for performing gene knock-out using episomal CRISPR/Cas9 targeting vectors. Using this approach, we generated distinct NHEJ-deficient pro-B cell lines and quantified V(D)J recombination levels in these cells. Furthermore, this methodology can be adapted to generate pro-B cell lines deficient for any gene suspected to play a role in V(D)J recombination, and more generally DSB repair., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Using salt mixtures instead of single salts can be beneficial for hydrophobic interaction chromatography (HIC). The effect of electrolytes on the adsorption of proteins, however, depends on the pH. Little is known on that dependence for mixed electrolytes. Therefore, the effect of the pH on protein adsorption from aqueous solutions containing mixed salts is systematically studied in the present work for a model system: the adsorption of bovine serum albumin (BSA) on the mildly hydrophobic resin Toyopearl PPG-600M. The pH is adjusted to 4.0, 4.7 or 7.0 using 25mM sodium phosphate or sodium citrate buffer. Binary and ternary salt mixtures of sodium chloride, ammonium chloride, sodium sulfate and ammonium sulfate as well as the pure salts are used at overall ionic strengths between 1500 and 4200mM. The temperature is always 25°C. The influence of the mixed electrolytes on the adsorption behavior of BSA changes completely with varying pH. Positive as well as negative cooperative effects of the mixed electrolytes are observed. The results are analyzed using a mathematical model which was recently introduced by our group. In that model the influence of the electrolytes is described by a Taylor series expansion in the individual ion molarities. After suitable parametrization using a subset of the data determined in the present work, the model successfully predicts the influence of mixed electrolytes on the protein adsorption. Furthermore, results for BSA from the present study are compared to literature data for lysozyme, which are available for the same adsorbent, temperature and salts. By calculating the ratio of the loading of the adsorbent for both proteins particularly favorable separation conditions can be selected. Hence, a model-based optimization of solvents for protein separation is possible., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Oxytocin (OXT) modulates several aspects of social behavior. Intranasal OXT is a leading candidate for treating social deficits in patients with autism spectrum disorder, and common genetic variants in the human OXTR gene are associated with emotion recognition, relationship quality, and autism spectrum disorder. Animal models have revealed that individual differences in Oxtr expression in the brain drive social behavior variation. Our understanding of how genetic variation contributes to brain OXTR expression is very limited., Methods: We investigated Oxtr expression in monogamous prairie voles, which have a well-characterized OXT system. We quantified brain region-specific levels of Oxtr messenger RNA and oxytocin receptor protein with established neuroanatomic methods. We used pyrosequencing to investigate allelic imbalance of Oxtr mRNA, a molecular signature of polymorphic genetic regulatory elements. We performed next-generation sequencing to discover variants in and near the Oxtr gene. We investigated social attachment using the partner preference test., Results: Our allelic imbalance data demonstrate that genetic variants contribute to individual differences in Oxtr expression, but only in particular brain regions, including the nucleus accumbens, where oxytocin receptor signaling facilitates social attachment. Next-generation sequencing identified one polymorphism in the Oxtr intron, near a putative cis-regulatory element, explaining 74% of the variance in striatal Oxtr expression specifically. Males homozygous for the high expressing allele display enhanced social attachment., Conclusions: Taken together, these findings provide convincing evidence for robust genetic influence on Oxtr expression and provide novel insights into how noncoding polymorphisms in OXTR might influence individual differences in human social cognition and behavior., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to social cognition, including parental behavior, social bonding, and individual recognition. Taken together, these studies in humans appear to provide compelling, but sometimes bewildering, evidence for the role of OT in influencing a vast array of complex social cognitive processes in humans. In this article, we investigate to what extent the human intranasal OT literature lends support to the hypothesis that intranasal OT consistently influences a wide spectrum of social behavior in humans. We do this by considering statistical features of studies within this field, including factors like statistical power, prestudy odds, and bias. Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects. Thus, the remarkable reports that intranasal OT influences a large number of human social behaviors should be viewed with healthy skepticism, and we make recommendations to improve the reliability of human OT studies in the future., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The influence of temperature on the adsorption of PEGylated lysozyme and pure PEG on Toyopearl PPG-600M, a hydrophobic resin, is studied by batch equilibrium measurements and pulse response experiments. Differently PEGylated lysozymes are used for the studies, enabling a systematic variation of the solute properties. Either ammonium sulfate or sodium chloride are added. The enthalpy of adsorption is calculated from a van't Hoff analysis based on these data. It is also directly measured by Isothermal Titration Calorimetry. In the investigated temperature range from 5 °C to 35 °C adsorption is favored by higher temperatures and hence endothermic. The results of the van't Hoff analysis of the equilibrium and the pulse response data agree well. Discrepancies between enthalpies of adsorption obtained by calorimetry and van't Hoff analysis are found and discussed. We conclude that the most likely explanation is that thermodynamic equilibrium is not reached in the experiments even though they were carried out carefully and in the generally accepted way., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To explore clinicians' views on antibiotic and/or steroid 'rescue packs' used as self-treatment for patients with exacerbations of COPD., Methods: 21 focus groups conducted in 7 countries--Netherlands, Russia, Norway, China (Hong Kong), Wales, Germany and Poland involving 142 primary care clinicians and pulmonologists., Results: We found wide variation in reported use of and attitudes to self-treatment among GPs and pulmonologists in the participating countries. Clinicians highlighted the importance of identifying patients who were most likely to benefit (those with more severe disease) and most likely to use the treatment appropriately (demonstrated by previous behaviour), and the importance of adequate patient education and ongoing communication in regard to use of self-treatment packs. Clinicians recognised patient empowerment and facilitating prompt treatment as potential benefits of self-treatment. However, many felt they did not have the time or resources for appropriate patient selection and education., Conclusion: Clinicians do not feel it is appropriate to offer self-treatment rescue packs to all patients routinely without careful consideration of patient understanding of their illness and their capacity for self-management., Practice Implications: Adequate resources and continuity of patient care are required for clinicians to feel confident in the safe and effective implementation of this strategy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A novel nuclear magnetic resonance (NMR) probe head for monitoring fast chemical reactions is described. It combines micro-reaction technology with capillary flow NMR spectroscopy. Two reactants are fed separately into the probe head where they are effectively mixed in a micro-mixer. The mixed reactants then pass through a capillary NMR flow cell that is equipped with a solenoidal radiofrequency coil where the NMR signal is acquired. The whole flow path of the reactants is thermostatted using the liquid FC-43 (perfluorotributylamine) so that exothermic and endothermic reactions can be studied under almost isothermal conditions. The set-up enables kinetic investigation of reactions with time constants of only a few seconds. Non-reactive mixing experiments carried out with the new probe head demonstrate that it facilitates the acquisition of constant highly resolved NMR signals suitable for quantification of different species in technical mixtures. Reaction kinetic measurements on a test system are presented that prove the applicability of the novel NMR probe head for monitoring fast reactions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The influence of mixed electrolytes on the adsorption of macromolecules on a hydrophobic resin is explored. The macromolecules are native lysozyme, di-PEG-lysozyme-5kDa and pure PEG-6kDa, the adsorbent is Toyopearl PPG-600M, a mildly hydrophobic resin. The solvent is a 25 mM aqueous sodium phosphate buffer at pH 7.0 containing additional salts with an overall ionic strength of 3000 mM. The studied salts are sodium chloride, ammonium sulfate, sodium sulfate and ammonium chloride. Both pure salts as well as binary and ternary mixtures of these salts with varying ratios of the amounts of the salts are studied. For all solvents adsorption equilibrium isotherms are measured at 25°C. Mixing electrolytes can lead to synergetic effects, i.e. the adsorption in the mixed electrolyte system is sometimes distinctly larger than expected from the results of the single electrolyte systems. The single ions, not the salts, drive the adsorption. A mathematical model is developed, which describes the influence of the different ions and their cross-interactions on the studied adsorption process., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: High-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance. Education of physicians and patients can lower prescribing levels, but it frequently relies on highly trained staff. We assessed whether internet-based training methods could alter prescribing practices in multiple health-care systems., Methods: After a baseline audit in October to December, 2010, primary-care practices in six European countries were cluster randomised to usual care, training in the use of a C-reactive protein (CRP) test at point of care, in enhanced communication skills, or in both CRP and enhanced communication. Patients were recruited from February to May, 2011. This trial is registered, number ISRCTN99871214., Results: The baseline audit, done in 259 practices, provided data for 6771 patients with lower-respiratory-tract infections (3742 [55·3%]) and upper-respiratory-tract infections (1416 [20·9%]), of whom 5355 (79·1%) were prescribed antibiotics. After randomisation, 246 practices were included and 4264 patients were recruited. The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0·54, 95% CI 0·42-0·69) and with enhanced-communication training than without (36% vs 45%, 0·69, 0·54-0·87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0·53, 95% CI 0·36-0·74, p<0·0001; enhanced communication 0·68, 0·50-0·89, p=0·003; combined 0·38, 0·25-0·55, p<0·0001)., Interpretation: Internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries., Funding: European Commission Framework Programme 6, National Institute for Health Research, Research Foundation Flanders., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The adsorption of native bovine serum albumin (BSA) and 12 kDa-PEG-BSA on 12 different commercially available strong and weak anion-exchange resins is studied at 25 °C and pH 7. The resins differ in their base matrix material, their functional groups and the type of polymer modification. A combination of equilibrium measurements and microcalorimetric experiments is used to determine the specific enthalpy of adsorption of the proteins. From these data, the entropic contributions to the specific Gibbs energy of adsorption are determined. The results strongly differ for different resins. They also depend on the loadings. The adsorption of BSA on strong (Q) anion-exchangers is exothermic and enthalpy-driven. The adsorption of BSA on weak (DEAE) anion-exchangers is endothermic and entropy-driven. The adsorption of PEG-BSA on strong (Q) anion-exchangers is exothermic or endothermic, depending on the resin, while the adsorption of PEG-BSA on weak (DEAE) anion-exchangers is exothermic for all studied resins. The present study provides a large body of new experimental data that contribute to the understanding of the nature of protein adsorption on ion exchange resins and the influence of the resin properties and polymer modification of the proteins on this process., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Pulse oximetry has become an important tool in evaluating, and monitoring pulmonary diseases, but the knowledge about arterial oxygen saturation (SpO(2)) values in a general population is limited. The aim of this study was to describe the distribution of low pulse oximetry values in a general adult population and their association with certain predictors., Methods: A cross-sectional population based survey was performed in Tromsø, Norway, in 2007-2008. Valid SpO(2) and pre-bronchodilator spirometry was recorded in 6317 participants aged 38-87 years (57% women). Resting SpO(2) ≤95% was defined as an abnormal value. Predictors of SpO(2) ≤95% with p < 0.05 were entered into a binary multivariable logistic regression., Results: The prevalence of SpO(2) ≤95% was 6.3%. The strongest predictors in the logistic regression were increased body mass index (BMI) (OR of BMI ≥35 = 6.2, CI(4.2, 9.2)), and reduced forced expiratory volume in 1 s (FEV(1)) % predicted (OR of FEV1% predicted <50 = 4.1, CI(2.5, 6.7)), followed by increased age, male gender, and smoking (p < 0.001). Other significant predictors were elevated C-reactive protein (CRP) (p < 0.005), former smoking, breathlessness and elevated hemoglobin (p < 0.01)., Conclusion: Airflow limitation and other known signs of pulmonary diseases were, as expected, strongly associated with decreased oxygen saturation. Obesity was also a strong predictor of low SpO(2), and should be included among possible explanations when low SpO(2) values are encountered., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Extrahepatic portal vein obstruction can have severe health consequences. Variceal bleeding associated with this disorder causes upper gastrointestinal bleeding, leading to substantial morbidity and mortality. We report the clinical transplantation of a deceased donor iliac vein graft repopulated with recipient autologous stem cells in a patient with extrahepatic portal vein obstruction., Methods: A 10 year old girl with extrahepatic portal vein obstruction was admitted to the Sahlgrenska University Hospital in Gothenburg, Sweden, for a bypass procedure between the superior mesenteric vein and the intrahepatic left portal vein (meso Rex bypass). A 9 cm segment of allogeneic donor iliac vein was decellularised and subsequently recellularised with endothelial and smooth muscle cells differentiated from stem cells obtained from the bone marrow of the recipient. This graft was used because the patient's umbilical vein was not suitable and other strategies (eg, liver transplantation) require lifelong immunosuppression., Findings: The graft immediately provided the recipient with a functional blood supply (25-30 cm/s in the portal vein and 40 mL/s in the artery was measured intraoperatively and confirmed with ultrasound). The patient had normal laboratory values for 9 months. However, at 1 year the blood flow was low and, on exploration, the shunt was patent but too narrow due to mechanical obstruction of tissue in the mesocolon. Once the tissue causing the compression was removed the graft dilated. We therefore used a second stem-cell populated vein graft to lengthen the previous graft. After this second operation, the portal pressure was reduced from 20 mm Hg to 13 mm Hg and blood flow was 25-40 cm/s in the portal vein. With restored portal circulation the patient has substantially improved physical and mental function and growth. The patient has no anti-endothelial cell antibodies and is receiving no immunosuppressive drugs., Interpretation: An acellularised deceased donor vein graft recellularised with autologous stem cells can be considered for patients in need of vascular vein shunts without the need for immunosuppression., Funding: Swedish Government., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: In specific vole and primate species the neuropeptide oxytocin plays a central role in the regulation of pair-bonding behavior. Here we investigate the extent to which genetic variants in the oxytocin receptor gene (OXTR) are associated with pair-bonding and related social behaviors in humans., Methods: We first genotyped twelve single nucleotide polymorphisms (SNPs) in the TOSS (Twin and Offspring Study in Sweden) (n = 2309) and the TCHAD (Swedish Twin Study of Child and Adolescent Development) (n = 1240), comprising measures of self-reported pair-bonding behavior. In the TOSS sample we further investigated one of the SNPs for measures of marital status and quality. Moreover, in the TCHAD sample we explored the longitudinal relationship between precursors of pair-bonding during childhood and subsequent behavior in romantic relationships. Finally, in the TCHAD study and in the Child and Adolescent Twin Study of Sweden (CATSS) (n = 1771), the association between the same SNP and childhood behaviors was investigated., Results: One SNP (rs7632287) in OXTR was associated with traits reflecting pair-bonding in women in the TOSS and TCHAD samples. In girls the rs7632287 SNP was further associated with childhood social problems, which longitudinally predicted pair-bonding behavior in the TCHAD sample. This association was replicated in the CATSS sample in which an association between the same SNP and social interaction deficit symptoms from the autism spectrum was detected., Conclusion: These results suggest an association between variation in OXTR and human pair-bonding and other social behaviors, possibly indicating that the well-described influence of oxytocin on affiliative behavior in voles could also be of importance for humans.

Adsorption of native as well as mono-, di-, and tri-PEGylated lysozyme on Toyopearl Gigacap S-650M in sodium phosphate buffer is studied by isothermal titration calorimetry and by independent adsorption equilibrium measurements at pH 6 and 25°C. The production and separation of PEGylated lysozyme is discussed. Two different PEG sizes are used (5 kDa and 10 kDa) which leads to six different forms of PEGylated lysozyme which were systematically studied. The sodium chloride concentration is varied according to the elution conditions in the production process. The specific enthalpy of adsorption Δh(p)(ads) is determined from the calorimetric and the adsorption equilibrium data. It was found to be exothermal and constant with increasing adsorber loading for native lysozyme. For all PEGylated forms there is an influence of the adsorber loading on Δh(p)(ads) which is found to become more important with increasing PEGylation degree (total molecular weight of conjugated PEG). At low loadings the adsorption of all PEGylated lysozyme forms is exothermal. With increasing loading the adsorption becomes less exothermal and for the species with higher PEGylation degree also endothermal effects are observed at higher loadings. A thermodynamic analysis is carried out by which the enthalpic and entropic contributions to the binding constants are quantified. The findings are discussed on a molecular level. The results provide insight into the adsorption mechanisms of polymer-modified proteins on chromatographic resins., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Adsorption of two human monoclonal antibodies on two different strong cation exchange resins is studied by isothermal titration microcalorimetry and independent adsorption isotherm measurements. The pH value is varied between 4.5 and 7.0, using different buffer systems, the temperature is always 25 degrees C. The adsorption isotherm data is fitted using two different Langmuir type models. Combining the calorimetric and the adsorption data, the specific enthalpy of adsorption of the protein Deltah(p)(ads) is determined. At pH values near 7.0, where the antibodies are only weakly charged, the adsorption is exothermal. At small loadings the absolute number of Deltah(p)(ads) is then large and almost constant but it significantly decreases at higher loadings. This shows that the arrangement of antibody molecules on the absorber material depends on the loading and is less favourable at higher loadings. Despite the high positive charge of the antibody at pH values of about 5 the value of Deltah(p)(ads) is almost zero along the entire isotherm. Furthermore, at pH 4.5 even endothermal effects are observed, although high binding capacities are found. At these conditions the adsorption process seems to be strongly influenced by the ions bound to the antibody. Their release upon absorption explains the endothermal caloric effect. The adsorption equilibrium constant K(eq) is calculated from the isotherms. From Deltag(p)(ads) and the calorimetric results for Deltah(p)(ads), Deltas(p)(ads), the entropy change upon adsorption of the protein is found for the different studied conditions.

Background: Some authors have suggested that the background of alexithymia is related to affective development during early childhood., Objective: Authors studied the associations between alexithymia and childhood emotional neglect and sexual and physical abuse, also taking into account the significance of concomitant psychopathology., Method: Associations between childhood difficulties and adulthood alexithymia were studied with samples of primary-care (N=1,033) and mental-health center (N=243) outpatients assessed by The Toronto Alexithymia Scale and questionnaires for depressive, manic, and psychotic symptoms, and childhood difficulties., Results: No association between alexithymia and childhood abuse was found in mental-health center patients. Among primary-care patients, alexithymia total score and difficulty in identifying feelings and difficulty in describing feelings were associated with childhood emotional, sexual, and physical abuse., Conclusion: After controlling for psychopathology, there still remained an association with difficulty in identifying feelings and most abuse and neglect variables. These findings serve to strengthen the theory of alexithymia as a developmental process starting in childhood.

Background: Bronchial airflow limitation is a known predictor of raised C-reactive protein (CRP) level. The aim of this study was to explore this association in an elderly population, as well as the influence of other known and possible predictors of the CRP level, like smoking and the use of statins and inhaled corticosteroids., Population and Methods: The study population consists of 3877 Norwegians aged 60 years or more who took part in the fifth Tromsø study in 2001, a cross-sectional study. The examinations included questionnaires, spirometry and the measurement of CRP., Results: A geometric mean CRP value of 3.15 mg/L was found in subjects with severe airflow limitation (FEV(1)%<50 predicted and FEV(1)/FVC<70%), compared to 1.64 mg/L in subjects with normal spirometry, (p<0.001), and 19% of the subjects with severe airflow limitation had a CRP value above 10 mg/L compared to 4.9% in those with mild airflow limitation or normal spirometry. Elevated body mass index (BMI), smoking, hormone replacement therapy, and increasing age, were also strong independent predictors of increased CRP. Statin use was a strong predictor of decreased CRP level, while the use of inhaled corticosteroids was not associated with decreased CRP values., Conclusion: We found a strong link between bronchial airflow limitation and the circulating CRP level in an elderly population, independent of self-reported diseases, medication, smoking, and elevated BMI. The CRP value increased with increasing age in men, but not in women, which may be partly explained by a greater impact of chronic obstructive pulmonary disease (COPD) morbidity on the CRP level in men than in women. Measuring CRP may show to be a useful part of the diagnostic work-up in COPD patients.

Background: Chronic obstructive pulmonary disease (COPD) can be diagnosed when the FEV(1)/FVC ratio is below 70%, according to global initiative for chronic obstructive lung disease (GOLD). COPD is known as a disease which is frequently under-diagnosed. However, there is a risk of over diagnosis when this diagnostic threshold is applied among the elderly., Aims: To contribute to the discussion about the criteria for diagnosing COPD, by describing lung function and pulmonary symptoms in a population aged 60 years or more, and in particular the changes in the mean and 5% percentile of the FEV(1)/FVC ratio by increasing age., Methods: A cross sectional population-based study was performed in the city of Tromsø, Norway, in 2001-2002. Spirometry was performed in 4102 people 60 years and older (54.6% women), who also filled in a questionnaire., Results: Decreased FEV(1)% predicted and FEV(1)/FVC ratio were associated with smoking, increasing age, and reported pulmonary and cardiovascular diseases. Dyspnoea and coughing were also strongly associated with smoking and reported pulmonary and cardiovascular diseases, but coughing did not become more frequent by increasing age. In never smokers aged 60-69 years the frequency of FEV(1)/FVC ratio<70% was approximately 7% compared to 16-18% in those 70 years or more (p<0.001). FEV(1)/FVC ratio<70% among never smokers aged 60-69 years was just as frequent as FEV(1)/FVC ratio <65% in never smokers older than 70 years., Conclusion: Adjustments of the GOLD criteria for diagnosing COPD are needed, and FEV(1)/FVC ratios down to 65% should be regarded as normal when aged 70 years and older.

Dopamine antagonists, such as metoclopramide and domperidone, and the motilin receptor agonist erythromycin have been the cornerstones in drug treatment of severe gastroparesis for more than a decade. No new drugs have been approved for treatment of this disorder in this period. Instead, the 5-HT4 agonist cisapride has been withdrawn due to side-effects. The effectiveness of intrapyloric botulinum toxin for gastroparesis remains to be shown. In the last decade, gastric electrical stimulation (GES) with a fully implantable device has evolved as a promising treatment, with significant effects on nausea and vomiting in most patients with severe, drug-refractory diabetic gastroparesis and postsurgical gastroparesis. A proportion of patients with severe idiopathic gastroparesis and patients with idiopathic nausea and vomiting also respond. More research is needed to achieve precise selection of responders/non-responders to GES, and to study the potential benefit of GES in other patient groups suffering from severe nausea or vomiting.

Objective: To address the role of alcohol intake and tobacco smoking and the combination of the two on subsequent risk of Dupuytren's disease., Study Design and Setting: Cohort study of 7,254 subjects enrolled in the Copenhagen City Heart Study (1981-1983). Both self-reported information on lifestyle and objective measures at the baseline examination were linked to presence of Dupuytren's disease at a subsequent examination (1991-1994) using multivariate logistic regression analysis., Results: A total of 772 subjects had signs of Dupuytren's disease at follow-up. After adjustment for age, sex, educational level, diabetes, and either alcohol or tobacco consumption, respectively, odds ratios for having the disease increased in a dose-dependent manner with increasing levels of alcohol or tobacco intake; however, there was no statistical interaction between heavy smoking and heavy drinking., Conclusion: Alcohol intake and tobacco smoking are independently associated with increased risk of Dupuytren's disease, and the combination of the two conveys a very large risk.

On-line nuclear magnetic resonance spectroscopy (on-line NMR) is a powerful technique for reaction and process monitoring. Different set-ups for direct coupling of reaction and separation equipment with on-line NMR spectroscopy are described. NMR spectroscopy can be used to obtain both qualitative and quantitative information from complex reacting multicomponent mixtures for equilibrium or reaction kinetic studies. Commercial NMR probes can be used at pressures up to 35 MPa and temperatures up to 400 K. Applications are presented for studies of equilibria and kinetics of complex formaldehyde-containing mixtures as well as homogeneously and heterogeneously catalyzed esterification kinetics. Direct coupling of a thin-film evaporator is described as an example for the benefits of on-line NMR spectroscopy in process monitoring.