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Abstract Background Correct classification of estrogen receptor (ER) status is essential for prognosis and treatment planning in patients with breast cancer (BC). Therefore, it is recommended to sample tumor tissue from an accessible metastasis. However, ER expression can show intra- and intertumoral heterogeneity. 16α-[18F]fluoroestradiol ([18F]FES) Positron Emission Tomography/Computed Tomography (PET/CT) allows noninvasive whole-body (WB) identification of ER distribution and is usually performed as a single static image 60 min after radiotracer injection. Using dynamic whole-body (D-WB) PET imaging, we examine [18F]FES kinetics and explore whether Patlak parametric images ( $${K}_{i}$$ K i ) are quantitative and improve lesion visibility. Results This prospective study included eight patients with metastatic ER-positive BC scanned using a D-WB PET acquisition protocol. The kinetics of [18F]FES were best characterized by the irreversible two-tissue compartment model in tumor lesions and in the majority of organ tissues. $${K}_{i}$$ K i values from Patlak parametric images correlated with $${K}_{i}$$ K i values from the full kinetic analysis, r2 = 0.77, and with the semiquantitative mean standardized uptake value (SUVmean), r2 = 0.91. Furthermore, parametric $${K}_{i}$$ K i images had the highest target-to-background ratio (TBR) in 162/164 metastatic lesions and the highest contrast-to-noise ratio (CNR) in 99/164 lesions compared to conventional SUV images. TBR was 2.45 (95% confidence interval (CI): 2.25–2.68) and CNR 1.17 (95% CI: 1.08–1.26) times higher in $${K}_{i}$$ K i images compared to SUV images. These quantitative differences were seen as reduced background activity in the $${K}_{i}$$ K i images. Conclusion [18F]FES uptake is best described by an irreversible two-tissue compartment model. D-WB [18F]FES PET/CT scans can be used for direct reconstruction of parametric $${K}_{i}$$ K i images, with superior lesion visibility and $${K}_{i}$$ K i values comparable to $${K}_{i}$$ K i values found from full kinetic analyses. This may aid correct ER classification and treatment decisions. Trial registration ClinicalTrials.gov: NCT04150731, https://clinicaltrials.gov/study/NCT04150731

Introduction To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c 120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5–

These datasets contain measures from multi-modal data sources. They include objective and subjective measures commonly used to determine cognitive states of workload, situational awareness, stress, and fatigue using data collection tools such as NASA-TLX, SART, eye tracking, EEG, Health Monitoring Watch, a survey to assess training, and a think-aloud situational awareness assessment following the SPAM methodology. Also, data from a simulation formaldehyde production plant based on the interaction of the participants in a controlled control room experimental setting is included. The interaction with the plant is based on a human-in-the-loop alarm handling and process control task flow, which includes Monitoring, Alarm Handling, Recovery planning, and intervention (Troubleshooting, Control and Evaluation). Data was collected from 92 participants, split into four groups while they underwent the described task flow. Each participant tested three scenarios lasting 15–18 min with a –10-min survey completion and break period in between using different combinations of decision support tools. The decision support tools tested and varied for each group include alarm prioritisation vs. none, paper-based vs. Digitised screen-based procedures, and an AI recommendation system. This is relevant to compare current practices in the industry and the impact on operators’ performance and safety. It is also applicable to validate proposed solutions for the industry. A statistical analysis was performed on the dataset to compare the outcomes of the different groups. Decision-makers can use these datasets for control room design and optimisation, process safety engineers, system engineers, human factors engineers, all in process industries, and researchers in similar or close domains.

Introduction: Obsessive-compulsive disorder (OCD) has been associated with abnormal brain activation in regions related to response inhibition, such as the dorsal anterior cingulate cortex (dACC), as well as dysregulation of the glutamate system. We studied how the neurometabolites glutamate and glutamine (Glx) in the dACC are related to task performance and task-related brain activation during a response inhibition task in OCD patients and healthy controls (HC). Methods: We combined resting-state magnetic resonance spectroscopy (1H-MRS) in the dACC and functional MRI (fMRI) during the Stop Signal Task (SST), using data from two sites (43 OCD patients and 41 HC). For fMRI data, region of interest (ROI) and whole brain analyses were performed during successful inhibition and error processing. Subsequently, the relation between baseline Glx concentrations, task-related activation, functional connectivity, and task performance was tested using correlational analyses. Results: In HC, Glx concentration in dACC showed a positive correlation with inhibition-related activation in the right thalamus (based on ROI analyses) and the brain stem (based on whole brain analyses). No relation between Glx and task-related activation was observed in patients with OCD. SST performance was not different between groups and was not associated with dACC Glx concentrations. Limitations: Although we attempted to link neurometabolite levels and brain activation, the non-simultaneous acquisition of 1H-MRS with fMRI made it difficult to interpret the results. Conclusions: We conclude that dACC Glx is associated with inhibition-related activation and network function in HC, but not in OCD, suggesting altered inhibition processing in OCD.

BackgroundIn Norway, the introduction of an interdisciplinary subject named Public Health and Life skills has brought about renewed attention to how health is conceptualized and taught within and across school subjects. Physical education (PE) is one subject that has traditionally been linked to health outcomes. However, a narrow focus on increased physical activity as the main outcome of PE could be counterproductive in the pursuit of health. Critical health literacy (CHL) is put forward as a resource for health that can be nurtured in the PE context; this study hypothesizes that academic achievement in PE is positively associated with some aspects of CHL.MethodsThis cross-sectional study included 521 pupils aged 13–15 years old from five lower secondary schools in Norway. Structural equation models were used as the primary statistical analysis to test the hypothesis. The study controlled for parents’ education, leisure physical activity, and participation in sports club activities.ResultsThe results confirm the hypothesis, showing a positive and significant association between PE and CHL. The association remains when controlling for parents’ education, leisure physical activity, and participation in sports club activities (β^PE→CHL−C1 = 0.264, p = 0.001; β^PE→CHL−C2 = 0.351, p

Immunotherapy using checkpoint inhibitors targeting the interaction between PD-1 on T cells and PD-L1 on cancer cells has shown significant results in non-small-cell lung cancer (NSCLC). Not all patients respond to the therapy, and PD-L1 expression heterogeneity is proposed to be one determinant for this. The alternative processing of PD-L1 RNA, which depends on an alternative poly-A site in intron 4, generates a shorter mRNA variant (PD-L1v4) encoding soluble PD-L1 (sPD-L1), relative to the canonical PD-L1v1 mRNA encoding membrane-associated PD-L1 (mPD-L1). This study aimed to identify factors influencing the ratio between these two PD-L1 mRNAs in NSCLC cells. First, we verified the existence of the alternative PD-L1 RNA processing in NSCLC cells, and from in silico analyses, we identified a candidate list of regulatory factors. Examining selected candidates showed that CRISPR/Cas9-generated loss-of-function mutations in CDK12 increased the PD-L1v4/PD-L1v1 mRNA ratio and, accordingly, the sPD-L1/mPD-L1 balance. The CDK12/13 inhibitor THZ531 could also increase the PD-L1v4/PD-L1v1 mRNA ratio and impact the PD-L1 transcriptional response to IFN-γ stimulation. The fact that CDK12 regulates PD-L1 transcript variant formation in NSCLC cells is consistent with CDK12’s role in promoting transcriptional elongation over intron-located poly-A sites. This study lays the groundwork for clinical investigations to delineate the implications of the CDK12-mediated balancing of sPD-L1 relative to mPD-L1 for immunotherapeutic responses in NSCLC.

Abstract Large herbivores are often classed as ecosystem engineers, and when they become scarce or overabundant, this can alter ecosystem states and influence climate forcing potentials. This realization has spurred a call to integrate large herbivores in earth system models. However, we lack a good understanding of their net effects on climate forcing, including carbon and energy exchange. A possible solution to this lies in harmonizing data across the myriad of large herbivore exclosure experiments around the world. This is challenging due to differences in experimental designs and field protocols. We used airborne laser scanning (ALS) to describe the effect of herbivore removal across 43 young boreal forest stands in Norway and found that exclusion caused the canopy height to increase from 1.7 ± 0.2 to 2.5 ± 0.2 m (means ± se), and also causing a marked increase in vertical complexity and above‐ground biomass. We then go on to discuss some of the issues with using ALS; we propose ALS as an approach for studying the effects of multiple large herbivore exclosure experiments simultaneously, and producing area‐based estimates on canopy structure and forest biomass in a cheap, efficient, standardized and reproducible way. We suggest that this is a vital next step towards generating biome‐wide predictions for the effects of large herbivores on forest ecosystem structure which can both inform both local management goals and earth system models.

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via ‘Proteomics of Isolated Chromatin fragments’, applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.

Abstract Background Interventions directed at after school programs (ASPs) have the potential to support physical activity (PA) in young children. Research has indicated that interventions that emphasize competence building among the ASP staff can lead to increased PA among the children. The present study evaluates the effectiveness of the Active Play in ASP intervention—a program for ASP staff aimed at supporting physical activity among first graders in ASP. Methods We used a matched-pair cluster randomized design and included 456 first graders from 14 schools in Norway. From these, 7 ASPs received the intervention (N = 229), while 7 acted as controls (N = 227). Measurements were taken at baseline, immediately post intervention (7 month follow-up) and after a year (19 month follow-up). The primary outcome was moderate to vigorous physical activity (MVPA), which was estimated with predefined cut points of counts per minute (CPM) and expressed as minutes/hour. Secondary outcomes were vigorous and light intensity physical activity (VPA and LPA) and sedentary behavior. The analyses of intervention effects were based on between-group differences in outcome changes between the 3 measurement points and were conducted using a mixed-effects model for repeated measures using categorical time. In exploratory analyses, we investigated gender, baseline body mass index, and baseline CPM as potential effect modifiers. Results No significant intervention effects was observed on MVPA (0.55 min/hour [99% CI -0.55:1.64]) or on the secondary outcomes, min/hour of LPA, VPA or sedentary behavior. Exploratory analyses indicated that among the 50% least physically active children at baseline, children in intervention ASPs reduced sedentary time from baseline to 19 months follow up by 1.67 min/hour (95% CI -3.12:-0.21) compared to the controls. Conclusions Although the intervention did not significantly increase the mean MVPA among the children in the intervention ASPs compared to controls, it did seem to have a small effect by reducing sedentary behavior time among the least active children. An even stronger emphasis on how to identify less active children and support their activity may be needed in order to increase their PA and further reduce sedentary behavior time. Trial registration ClinicalTrials; NCT02954614 , Registered 3 November 2016, −Retrospectively registered, first participant enrolled August 2016

IntroductionCardiovascular dysfunction is a potentially lethal complication of hypothermia. Due to a knowledge gap, pharmacological interventions are not recommended at core temperatures below 30°C. Yet, further cooling is induced in surgical procedures and survival of accidental hypothermia is reported after rewarming from below 15°C, advocating a need for evidence-based treatment guidelines. In vivo studies have proposed vasodilation and afterload reduction through arteriole smooth muscle cGMP-elevation as a favorable strategy to prevent cardiovascular dysfunction in hypothermia. Further development of treatment guidelines demand information about temperature-dependent changes in pharmacological effects of clinically relevant vasodilators.Materials and MethodsHuman phosphodiesterase-enzymes and inverted erythrocytes were utilized to evaluate how vasodilators sildenafil and vardenafil affected cellular efflux and enzymatic breakdown of cAMP and cGMP, at 37°C, 34°C, 32°C, 28°C, 24°C, and 20°C. The ability of both drugs to reach their cytosolic site of action was assessed at the same temperatures. IC50- and Ki-values were calculated from dose–response curves at all temperatures, to evaluate temperature-dependent effects of both drugs.ResultsBoth drugs were able to reach the intracellular space at all hypothermic temperatures, with no reduction compared to normothermia. Sildenafil IC50 and Ki-values increased during hypothermia for enzymatic breakdown of both cAMP (IC50: 122 ± 18.9 μM at 37°C vs. 269 ± 14.7 μM at 20°C, p < 0.05) and cGMP (IC50: 0.009 ± 0.000 μM at 37°C vs. 0.024 ± 0.004 μM at 32°C, p < 0.05), while no significant changes were detected for vardenafil. Neither of the drugs showed significant hypothermia-induced changes in IC50 and Ki–values for inhibition of cellular cAMP and cGMP efflux.ConclusionSildenafil and particularly vardenafil were ableto inhibit elimination of cGMP down to 20°C. As the cellular effects of these drugs can cause afterload reduction, they show potential in treating cardiovascular dysfunction during hypothermia. As in normothermia, both drugs showed higher selectivity for inhibition of cGMP-elimination than cAMP-elimination at low core temperatures, indicating that risk for cardiotoxic side effects is not increased by hypothermia.

It is unknown if the somatic mutations in chronic myeloproliferative neoplasms (MPNs), JAK2V617F and Calreticulin, are associated with oxidative stress, or impaired mitochondrial defense against reactive oxygen species. In the Danish General Suburban Population Study (GESUS), including 116 JAK2V617F-mutated, 8 CALR-mutated, and 3310 mutation-negative participants without overt MPN, and in a study of 39 patients with myelofibrosis, the most advances type of MPNs, and 179 matched controls, we compared the urinary concentration of oxidized nucleosides – 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) – as markers of oxidative stress. In GESUS, we performed Mendelian randomization analyses, using the Ala16Val single nucleotide polymorphism in the superoxide dismutase2 (SOD2) gene. In the multivariate analyses in GESUS, the 8-oxodG and 8-oxoGuo concentration were 13% (95%CI: 6–21%, p

Abstract Background Former studies on smoking as a risk factor for Philadelphia‐negative myeloproliferative neoplasms (MPNs) have mainly been carried out in women's cohorts and studies with various definitions of MPNs. Herein, we conducted a cohort study with register‐based follow‐up of a general population from Denmark, to validate and substantiate prior observations. Methods In the Danish Health Examination Survey cohort, we used the Cox proportional‐hazards model adjusted for age, sex, body mass index, and level of education, to calculate hazard ratios (HRs), to investigate, whether daily smokers or occasional/ex‐smokers had an increased risk of MPNs compared to never‐smokers. Results From the time of data collection (September 2007 to October 2008) until 1 January 2015, 70 individuals were diagnosed with MPNs among 75 896 study participants. Similar results were observed in both the age and sex adjusted analysis and the multivariable analysis. The multivariable HR of any MPN diagnosis for daily smokers was 2.5 (95% CI: 1.3‐5.0). For essential thrombocytosis, polycythemia vera, myelofibrosis, and MPN‐unclassified, the HRs were 1.8 (95% CI: 0.5‐5.8), 1.7 (95% CI: 0.5‐5.8), 4.3 (95% CI: 0.9‐19), and 6.2 (95% CI: 1.5‐25), respectively. Among occasional/ex‐smokers the corresponding HRs were 1.9 (95% CI: 1.1‐3.3), 1.5 (95% CI: 0.6‐3.7), 0.8 (95% CI: 0.3‐2.4), 0.9 (95% CI: 0.2‐4.4), and 6.2 (95% CI: 1.8‐21). Participants, who smoked >15 g/day, had an overall HR of 3.4 (95% CI: 1.4‐8.2) for any MPN diagnosis, while participants who smoked ≤15 g/day, had an overall HR of 2.1 (95% CI: 0.9‐4.7). Conclusion Smoking was associated with MPN development when comparing smokers and never‐smokers. Further studies investigating smoking in MPNs are warranted to substantiate our findings.

Abstract Background Opsins are G protein-coupled receptors used for both visual and non-visual photoreception, and these proteins evolutionarily date back to the base of the bilaterians. In the current sequencing age, phylogenomic analysis has proven to be a powerful tool, facilitating the increase in knowledge about diversity within the opsin subclasses and, so far, at least nine types of opsins have been identified. Within echinoderms, opsins have been studied in Echinoidea and Ophiuroidea, which do not possess proper image forming eyes, but rather widely dispersed dermal photoreceptors. However, most species of Asteroidea, the starfish, possess true eyes and studying them will shed light on the diversity of opsin usage within echinoderms and help resolve the evolutionary history of opsins. Results Using high-throughput RNA sequencing, we have sequenced and analyzed the transcriptomes of different Acanthaster planci tissue samples: eyes, radial nerve, tube feet and a mixture of tissues from other organs. At least ten opsins were identified, and eight of them were found significantly differentially expressed in both eyes and radial nerve, with R-opsin being the most highly expressed in the eye. Conclusion This study provides new important insight into the involvement of opsins in visual and nonvisual photoreception. Of relevance, we found the first indication of an r-opsin photopigment expressed in a well-developed visual eye in a deuterostome animal. Additionally, we provided tissue specific A. planci transcriptomes that will aid in future Evo Devo studies.

Abstract Lymph vessels counteract edema by transporting interstitial fluid from peripheral tissues to the large veins and serve as conduits for immune cells, cancer cells, and pathogens. Because edema during inflammation and malignancies is frequently associated with acidosis, we tested the hypothesis that acid‐base disturbances affect human thoracic duct contractions. We studied, by isometric and isobaric myography, the contractile function of human thoracic duct segments harvested with written informed consent from patients undergoing esophageal cancer surgery. Human thoracic ducts produce complex contractile patterns consisting of tonic rises in tension (isometric myography) or decreases in diameter (isobaric myography) with superimposed phasic contractions. Active tone development decreases substantially (~90% at 30 vs. 7 mmHg) at elevated transmural pressure. Acidosis inhibits spontaneous as well as noradrenaline‐ and serotonin‐induced phasic contractions of human thoracic ducts by 70–90% at extracellular pH 6.8 compared to 7.4 with less pronounced effects observed at pH 7.1. Mean tension responses to noradrenaline and serotonin – averaged over the entire period of agonist exposure – decrease by ~50% at extracellular pH 6.8. Elevating extracellular [K+] from the normal resting level around 4 mmol/L increases overall tension development but reduces phasic activity to a level that is no different between human thoracic duct segments investigated at normal and low extracellular pH. In conclusion, we show that extracellular acidosis inhibits human thoracic duct contractions with more pronounced effects on phasic than tonic contractions. We propose that reduced phasic activity of lymph vessels at low pH attenuates lymph propulsion and increases the risk of edema formation.

Background: While statins may have anti-inflammatory effects, anti-oxidative effects are controversial. We investigated if statin treatment is associated with differences in oxidatively generated nucleotide damage and chronic inflammation, and the relationship between nucleotide damage and chronic inflammation. Methods: We included 19,795 participants from the Danish General Suburban Population Study. In 3420 participants, we measured urinary 8-oxodG and 8-oxoGuo by liquid chromatography-tandem mass spectrometry as markers of oxidatively generated damage to DNA and RNA, respectively. We used a composite score for chronic inflammation (INFLA score) of hsCRP, WBC, platelet count, and neutrophil granulocyte to lymphocyte ratio. Associations were assessed using multivariate linear regression models. Results: Compared with non-users, statin users had 4.3–6.0% lower 8-oxodG in three separate models (p 60 y, statin users had 11.4% lower 8-oxodG (95%CI: 6.7–15.9%, pinteraction

Summary: Emerging picture of hantavirus infection in the South America is characterized by greater proportion of childhood infection and wider spectrum of disease from mild asymptomatic to lethal cardiopulmonary disease. Barbados is endemic for dengue and leptospirosis, both of which share clinical features with hantavirus infection and in many cases neither of these diagnosis could be confirmed. We investigate whether some of the children hospitalized with suspected dengue could indeed have been hantavirus infections. In this prospective study children hospitalized with suspected dengue were tested for hantavirus infection using ELISA for the IgM antibodies. Thirty-eight children tested positive for hantavirus infection. They presented with fever, headache and mild respiratory and gastrointestinal symptoms and signs. None of them had features suggestive of hantavirus cardiopulmonary syndrome. Blood count values ranged from low to normal to high for their age. There were no deaths. Hantavirus infection is prevalent in this Caribbean country. It predominantly presents with milder disease and is responsible for some of the nonspecific febrile illnesses in children. Keywords: Hantavirus infection, Children, Caribbean, Clinical features

Summary: Long-term seroprevalence studies of dengue have provided a measure of the degree of endemicity and future trends in disease prevalence and severity. In this study, we describe the seroprevalence of dengue antibodies in febrile persons with suspected acute dengue in Barbados. It is a retrospective population-based study of all febrile persons with suspected dengue from 2006 to 2013. All of the cases had IgM and IgG antibodies in the blood sample drawn between days 3 and 5 of their illness. Among the 8296 cases that were tested for IgM antibodies, 3037 (36.6%) had recent dengue infection. In the age groups 20 years, 23.3%, 39.6% and 35.5% had acute infection, respectively. Of the 7227 cases with documented IgG results, 5473 (75.7%) were positive and had a past infection. In the age groups 20 years, 31.2%, 65.2% and 86.6%, respectively, had a past infection (IgG positive). During the first 5 years of life, 10–20% of febrile persons investigated for dengue had a positive IgM and a negative IgG titer, between 5 and 10% had a positive IgM and IgG titer, 5% had a positive IgG and a negative IgM titer, and between 45% and 65% had a negative IgM and a negative IgG titer. Throughout the study period, between 12% and 20% of febrile persons failed to show any evidence of current or previous dengue. In the age groups 20 years, 45.0%, 18.8% and 7.2%, respectively, had no evidence of recent or past dengue (both IgM and IgG negative). Between 37% and 59% of the febrile persons had serological evidence of past dengue in the absence of any current dengue. In conclusion, the pattern of IgG antibodies in this study was comparable to those in countries known to be hyperendemic for dengue. The age of infection is likely to shift to younger adults and children who are more likely to have severe dengue in the future. Keywords: Dengue, Seroprevalence, Febrile, Caribbean

We investigated the relation between dimensional aspects of inattention and hyperactivity-impulsivity in childhood and peer problems 4 years later, as well as the potential mediating effects of intellectual function. The sample included 127 children (32 with attention-deficit/hyperactivity disorder). Symptoms of inattention and hyperactivity-impulsivity were assessed via parent and teacher reports on Swanson Nolan and Pelham-IV questionnaire. Peer problems were assessed by parent reports on the Strengths and Difficulties Questionnaire, and children's intellectual functioning by the third edition of the Wechsler Intelligence Scale for Children. Linear regressions showed a significant effect of inattention on future peer problems, partially mediated by slow processing speed. These effects remained significant when ADHD status was covaried. Findings highlight the importance of processing speed in explaining the predictive relation between childhood inattention and later peer problems. Inattention and processing speed in early childhood are potentially malleable factors influencing adolescent social functioning.

Species occurrence data records the location and time of an encounter with a species, and is valuable for many aspects of ecological and evolutionary analyses. A key distinction within species occurrence data is between (1) collected and preserved specimens that can be taxonomically validated (i.e., natural history collections), and (2) observations, which are more error prone but richer in terms of number and spread of observations. In this study we analyse the distribution in temporal, spatial, taxonomic and environmental coverage of specimen- and observation based species occurrence data for land plants in Norway, a region with strong climatic and human population density gradients. Of 4.8 million species occurrence records, the majority (78%) were observations. However, there was a greater species richness in the specimen record (N = 4691) than in the observation record (N = 3193) and most species were recorded more as specimens than observations. Specimen data was on average older, and collected later during the year. Both record types were highly influenced by a small number of prolific contributors. The species most highly represented in the observation data set were widespread or invasive, while in the specimen records, taxonomically challenging species were overrepresented. Species occurrence records were unevenly spatially distributed. Both specimen and observation records were concentrated in regions of Norway with high human population density and with high temperatures and precipitation, but in different regions within Norway. Observation and specimen records thus differ in taxonomic, temporal, spatial and environmental coverage for a well-sampled group and study region, potentially influencing the ecological inferences made from studies utilizing species occurrence data. The distribution of observation data dominates the dataset, so inferences of species diversity and distributions do not correspond to the evolutionary or physiological knowledge of species, which is based on specimen data. We make recommendations for users of biodiversity data, and collectors to better exploit the complementary strengths of these distinct biodiversity data types.

A growing body of research points to the value of multiple group memberships for individual well-being. However, much of this work considers group memberships very broadly and in terms of number alone. We conducted two correlational studies exploring how the relationship between multiple group membership and well-being is shaped by (a) the complexity of those groups within the overall self-concept (i.e., social identity complexity: SIC), and (b) the perceived value and visibility of individual group memberships to others (i.e., stigma). Study 1 (N = 112) found a positive relationship between multiple group membership and well-being, but only for individuals high in SIC. This effect was mediated by perceived identity expression and access to social support. Study 2 (N = 104) also found that multiple group memberships indirectly contributed to well-being via perceived identity expression and social support, as well as identity compatibility and perceived social inclusion. But, in this study the relationship between multiple group memberships and well-being outcomes was moderated by the perceived value and visibility of group memberships to others. Specifically, possessing multiple, devalued and visible group memberships compromised well-being relative to multiple valued group memberships, or devalued group memberships that were invisible. Together, these studies suggest that the benefits of multiple group membership depend on factors beyond their number. Specifically, the features of group memberships, individually and in combination, and the way in which these guide self-expression and social action, determine whether these are a benefit or burden for individual well-being.

The control of human Campylobacteriosis is a priority in public health agendas all over the world. Poultry is considered a significant risk factor for human infections with Campylobacter and risk assessment models indicate that the successful implementation of Campylobacter control strategies in poultry will translate on a reduction of human Campylobacteriosis cases. Efficient control strategies implemented during primary production will reduce the risk of Campylobacter introduction in chicken houses and/or decrease Campylobacter concentration in infected chickens and their products. Consequently, poultry producers need to make difficult decisions under conditions of uncertainty regarding the implementation of Campylobacter control strategies. This manuscript presents the development of probabilistic graphical models to support decision making in order to control Campylobacter in poultry. The decision support systems are constructed as probabilistic graphical models (PGMs) which integrate knowledge and use Bayesian methods to deal with uncertainty. This paper presents a specific model designed to integrate epidemiological knowledge from the United Kingdom (UK model) in order to assist poultry managers in specific decisions related to vaccination of commercial broilers for the control of Campylobacter. Epidemiological considerations and other crucial aspects including challenges associated with the quantitative part of the models are discussed in this manuscript. The outcome of the PGMs will depend on the qualitative and quantitative data included in the models. Results from the UK model and sensitivity analyses indicated that the financial variables (cost/reward functions) and the effectiveness of the control strategies considered in the UK model were driving the results. In fact, there were no or only small financial gains when using a hypothetical vaccine B (able to decrease Campylobacter numbers from two to six logs in 20% of the chickens with a cost of 0.025 £/chicken) and reward system 1 (based on similar gross profits in relation to Campylobacter levels) under the specific assumptions considered in the UK model. In contrast, significant reductions in expected Campylobacter numbers and substantial associated expected financial gains were obtained from this model when considering the reward system 2 (based on quite different gross profits in relation to Campylobacter levels) and the use of a hypothetical cost-effective vaccine C (able to reduce the level of Campylobacter from two to six logs in 90% of the chickens with a cost of 0.03 £/chicken). The flexibility of probabilistic graphical models allows for the inclusion of more than one Campylobacter vaccination strategy and more than one reward system and consequently, diverse potential solutions for the control of Campylobacter may be considered. Cost-effective Campylobacter control strategies that can significantly reduce the probability of Campylobacter introduction into a flock and/or the numbers of Campylobacter in already infected chickens, and translate to an attractive cost-reward balance will be preferred by poultry producers.

For cellular and animal transgenesis, FLP- and Cre-recombinase gene capture systems are highly effective to provide stable integration of a donor plasmid carrying the transgene cassette of interest into an engineered genomic locus in a given cell line. However, in many protocols, the entire plasmid bacterial backbone is integrated along with the transgene cassette. Here, we present a very simple yet highly efficient method for excluding plasmid bacterial backbone integration. The transgene cassette, including a single FLP recognition target site, is specifically amplified by PCR, and the resulting DNA ligated into minicircles can serve as donor DNA in FLP-mediated recombination. Interestingly, the elimination of the bacterial backbone increased expression of the inserted transgene. The presented method is simple and efficient for generating transgene cassette insertions devoid of the bacterial backbone.

We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis.

Incidentally discovered adrenal masses (incidentalomas) are common and present challenges both in diagnosis and management. When incidentally discovered adrenal masses are bilateral, a refined diagnostic approach is warranted since bilateral disease is more likely to be pathologic. We review a case of a 34-year-old man with incidentally discovered bilateral adrenal nodules. A comprehensive diagnostic strategy led to the diagnosis of bilateral pheochromocytoma caused by von Hippel-Lindau syndrome. He was successfully treated with bilateral laparoscopic adrenalectomy and has recovered well. While the initial diagnostic approach is similar to the unilateral incidentaloma, additional testing and/or genetic testing should be considered in the case of the bilateral adrenal mass.

Objective. Barbados, a small developing state at the end of the nutrition transition, faces an obesity epidemic. Although there is hope of stemming the epidemic in childhood, no descriptions of children's dietary and physical activity (PA) patterns are available for planning purposes. We describe the food and activity preferences and adult encouragement of active and sedentary behaviors for children 9–11 years in relation to weight status and the cultural context. Design. We used data from a pilot study preceding a large-scale ongoing study on the local drivers of the obesity epidemic among preadolescent children. PA, sedentary activity, and dietary intakes were assessed from recalls. Weight and height were measured. Setting. Barbados. Subjects. Sixty-two (62), 9–11-year-old school children. Results. Sugar-sweetened beverages provided 21% of energy consumed. Energy intake significantly explained BMI. Parents selected significantly more of children’s sedentary activities and encouraged mostly homework and chores (59%). Children’s self-selected school-based activity was significantly related to BMI. Conclusions. Childhood obesity prevention recommendations and research should focus on culture-specific practices that promote acquired taste for excess sugar and parent-child interactions regarding PA. Child influenced by school-based activity intervention may an important area for preventive intervention research.

Objectives. There are no published studies on the Barbados Emergency Ambulance Service and no assessment of the calls that end in nontransported individuals. We describe reasons for the nontransport of potential clients. Methods. We used the Emergency Medical Dispatch (Medical Priority Dispatch System) instrument, augmented with five local call types, to collect information on types of calls. The calls were categorised under 7 headings. Correlations between call types and response time were calculated. Results. Most calls were from the category medical (54%). Nineteen (19%) percent of calls were in the non-transported category. Calls from call type Cancelled accounted for most of these and this was related to response time, while Refused service was inversely related (). Conclusions. The Barbados Ambulance Service is mostly used by people with a known illness and for trauma cases. One-fifth of calls fall into a category where the ambulance is not used often due to cancellation which is related to response time. Other factors such as the use of alternative transport are also important. Further study to identify factors that contribute to the non-transported category of calls is necessary if improvements in service quality are to be made.

Background: Schools are important arenas for the promotion of critical health literacy (CHL) among adolescents. Key domains of CHL are information appraisal, understanding social determinants of health, and abilities to act on determinants of health. In this paper, we examine the psychometric properties of the Critical Health Literacy for Adolescents Questionnaire (CHLA-Q). Methods: A cross-sectional survey study was performed at 5 schools in Norway. Respondents included 522 pupils aged 13-15 years old. Confirmatory factor analysis (CFA) was conducted to examine the structural validity. Internal reliability was assessed using ordinal Cronbach's alpha. Results: The estimated model had acceptable closeness of fit. Five of 6 scales displayed adequate internal reliability. Conclusion: The results indicate acceptable fit of the CHLA-Q framework and that 5 of the 6 scales are applicable to inform future research and interventions. More research is needed on measurement of the second domain of CHL.

Background: The major objectives of this study were to evaluate the existing primary health care service provisions in the public and private sector and utilization of the services, and to assess the existing manpower and material resources. Methods: Data were collected through interviews with the primary health care providers. Data were also collected from the records maintained at the polyclinics and the Ministry of Health Statistics. An analysis and discussion of all the available data was conducted to develop a comprehensive primary health care service utilization and resources inventory at the polyclinics. Similar data were collected from the primary care providers in the private sector. Results: In the public sector, there are 8 polyclinics that provide primary health care to the children. All the polyclinics have immunization services and curative acute care. Some of the polyclinics have a range of services, including dental care, eye care, and rehabilitative care services that common to both adults and children. In the private sector, primary health care is delivered through the 76 private office and of the individual physicians and 11 grouped private practices. All of the private offices and group practices have curative acute care for children and some of the offices have immunization services. Over all 87.5% of all the immunizations were done at the polyclinics. Over all 60.1% of acute care visits were to the private sector and 39.9% to the public sector. In the public sector, 59.5% were under 5 years children while 40.5% were 5 years or older. The corresponding figures in the private care settings were 80.9% and 11.9%. Conclusions: The findings demonstrate the complimentary role of the public and the private sector in the primary health care of children in this country. While the private sector has a major role in the curative acute care of children, the public sector plays a pivotal role in the immunization services.

Aims: The aim was to demonstrate a method for automated image analysis of immunohistochemically stained tissue samples for extracting features that correlate with patient disease. We address the problem of quantifying tumor tissue and segmenting and counting cell nuclei. Materials and Methods: Our method utilizes a flexible segmentation method based on sparse coding trained from representative image samples. Nuclei counting is based on a nucleus model that takes size, shape, and nucleus probability into account. Nuclei clustering and overlays are resolved using a gray-weighted distance transform. We obtain a probability measure for pixels belonging to a nucleus from our segmentation procedure. Experiments are carried out on two sets of immunohistochemically stained images - one set based on the estrogen receptor (ER) and the other on antigen KI-67. For the nuclei separation we have selected 207 ER image samples from 58 tissue micro array-cores corresponding to 58 patients and 136 KI-67 image samples also from 58 cores. The images are hand-annotated by marking the center position of each nucleus. For the ER data we have a total of 1006 nuclei and for the KI-67 we have 796 nuclei. Segmentation performance was evaluated in terms of missing nuclei, falsely detected nuclei, and multiple detections. The proposed method is compared to state-of-the-art Bayesian classification. Statistical analysis used: The performance of the proposed method and a state-of-the-art algorithm including variations thereof is compared using the Wilcoxon rank sum test. Results: For both the ER experiment and the KI-67 experiment the proposed method exhibits lower error rates than the state-of-the-art method. Total error rates were 4.8 % and 7.7 % in the two experiments, corresponding to an average of 0.23 and 0.45 errors per image, respectively. The Wilcoxon rank sum tests show statistically significant improvements over the state-of-the-art method. Conclusions: We have demonstrated a method and obtained good performance compared to state-of-the-art nuclei separation. The segmentation procedure is simple, highly flexible, and we demonstrate how it, in addition to the nuclei separation, can perform precise segmentation of cancerous tissue. The complexity of the segmentation procedure is linear in the image size and the nuclei separation is linear in the number of nuclei. Additionally the method can be parallelized to obtain high-speed computations.