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Abstract Aims Describe the characteristics, management and outcomes of hospitalized ST-segment elevation myocardial infarction (STEMI) patients according to national ongoing myocardial infarction registries in Estonia, Hungary, Norway, and Sweden. Methods and results Country-level aggregated data was used to study baseline characteristics, use of in-hospital procedures, medications at discharge, in-hospital complications, 30-day and 1-year mortality for all patients admitted with STEMI during 2014–2017 using data from EMIR (Estonia; n = 4584), HUMIR (Hungary; n = 23 685), NORMI (Norway; n = 12 414, data for 2013–2016), and SWEDEHEART (Sweden; n = 23 342). Estonia and Hungary had a higher proportion of women, patients with hypertension, diabetes, and peripheral artery disease compared to Norway and Sweden. Rates of reperfusion varied from 75.7% in Estonia to 84.0% in Sweden. Rates of recommendation of discharge medications were generally high and similar. However, Estonia demonstrated the lowest rates of dual antiplatelet therapy (78.1%) and statins (86.5%). Norway had the lowest rates of beta-blockers (80.5%) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (61.5%). The 30-day mortality rates ranged between 9.9% and 13.4% remaining lowest in Sweden. One-year mortality rates ranged from 14.8% in Sweden and 16.0% in Norway to 20.6% in Hungary and 21.1% in Estonia. Age-adjusted lethality rates were highest for Hungary and lowest for Sweden. Conclusion This inter-country comparison of data from four national ongoing European registries provides new insights into the risk factors, management and outcomes of patients with STEMI. There are several possible reasons for the findings, including coverage of the registries and variability of baseline-characteristics’ definitions that need to be further explored.

Post-ingestive nutrient signals to the brain regulate eating behaviour in rodents, and impaired responses to these signals have been associated with pathological feeding behaviour and obesity. To study this in humans, we performed a single-blinded, randomized, controlled, crossover study in 30 humans with a healthy body weight (females N  = 12, males N  = 18) and 30 humans with obesity (females N  = 18, males N  = 12). We assessed the effect of intragastric glucose, lipid and water (noncaloric isovolumetric control) infusions on the primary endpoints cerebral neuronal activity and striatal dopamine release, as well as on the secondary endpoints plasma hormones and glucose, hunger scores and caloric intake. To study whether impaired responses in participants with obesity would be partially reversible with diet-induced weight loss, imaging was repeated after 10% diet-induced weight loss. We show that intragastric glucose and lipid infusions induce orosensory-independent and preference-independent, nutrient-specific cerebral neuronal activity and striatal dopamine release in lean participants. In contrast, participants with obesity have severely impaired brain responses to post-ingestive nutrients. Importantly, the impaired neuronal responses are not restored after diet-induced weight loss. Impaired neuronal responses to nutritional signals may contribute to overeating and obesity, and ongoing resistance to post-ingestive nutrient signals after significant weight loss may in part explain the high rate of weight regain after successful weight loss. Brain responses to food are severely diminished in individuals with obesity, and are not improved by 10% body weight loss. These findings point to an important role for the brain in weight regain after weight loss.

We present a detailed description of TOPAZ4, the latest version of TOPAZ – a coupled ocean-sea ice data assimilation system for the North Atlantic Ocean and Arctic. It is the only operational, large-scale ocean data assimilation system that uses the ensemble Kalman filter. This means that TOPAZ features a time-evolving, state-dependent estimate of the state error covariance. Based on results from the pilot MyOcean reanalysis for 2003–2008, we demonstrate that TOPAZ4 produces a realistic estimate of the ocean circulation in the North Atlantic and the sea-ice variability in the Arctic. We find that the ensemble spread for temperature and sea-level remains fairly constant throughout the reanalysis demonstrating that the data assimilation system is robust to ensemble collapse. Moreover, the ensemble spread for ice concentration is well correlated with the actual errors. This indicates that the ensemble statistics provide reliable state-dependent error estimates – a feature that is unique to ensemble-based data assimilation systems. We demonstrate that the quality of the reanalysis changes when different sea surface temperature products are assimilated, or when in-situ profiles below the ice in the Arctic Ocean are assimilated. We find that data assimilation improves the match to independent observations compared to a free model. Improvements are particularly noticeable for ice thickness, salinity in the Arctic, and temperature in the Fram Strait, but not for transport estimates or underwater temperature. At the same time, the pilot reanalysis has revealed several flaws in the system that have degraded its performance. Finally, we show that a simple bias estimation scheme can effectively detect the seasonal or constant bias in temperature and sea-level.

Solid fuel (SF) combustions, including coal and biomass, are important sources of pollutants in the particle and gas phase and therefore have significant implications for air quality, climate, and human health. In this study, we systematically examined gas-phase emissions, using the Vocus proton-transfer-reaction time-of-flight (PTR-TOF) mass spectrometer, from a variety of solid fuels, including beech logs, spruce/pine logs, spruce/pine branches and needles, straw, cow dung, and coal. The average emission factors (EFs) for organic vapors ranged from 4.8 to 74.2 g kg−1, depending on the combustion phases and solid fuel types. Despite slight differences in modified combustion efficiency (MCE) for some experiments, increasing EFs for organic vapors were observed with lower MCE. The relative contribution of different classes showed large similarities between the combustion phases in beech logs stove burning, relative to the large change in EFs observed. The CxHyOz family is the most abundant group of the organic vapor emitted from all SF combustion. However, among these SF combustions, a greater contribution of nitrogen-containing species and CxHy families (related to polycyclic aromatic hydrocarbons) is observed in the organic vapors from cow dung burning and coal burning, respectively. Intermediate-volatility organic compounds (IVOCs) constituted a significant fraction of emissions in solid fuel combustion, ranging from 12.6 % to 39.3 %. This was particularly notable in the combustion of spruce/pine branches and needles (39.3 %) and coal (31.1 %). Using the Mann–Whitney U test on the studied fuels, we identified specific potential new markers for these fuels based on the Vocus measurements. The product from pyrolysis of coniferyl-type lignin and the extract of cedar pine needle were identified as markers in the open burning of spruce/pine branches and needles (e.g., C10H14O2, C11H14O2, C10H10O2). The product (C9H12O) from the pyrolysis of beech lignin was identified as the potential new marker for beech log stove burning. Many series of nitrogen-containing homologues (e.g., C10H11–21NO, C12H11–21N, C11H11–23NO, and C15H15–31N) and nitrogen-containing species (e.g., acetonitrile, acrylonitrile, propanenitrile, methylpentanenitrile) were specifically identified in cow dung burning emissions. Polycyclic aromatic hydrocarbons (PAHs) with 9–12 carbons were identified with significantly higher abundance from coal burning compared to emissions from other studied fuels. The composition of these organic vapors reflects the burned solid fuel types and can help constrain emissions of solid fuel burning in regional models.

Background Most breast cancer patients undergoing mastectomy are candidates for breast reconstruction. Deciding about breast reconstruction is complex and the preference-sensitive nature of this decision requires an approach of shared decision making between patient and doctor. Women considering breast reconstruction have expressed a need for decision support. We developed an online patient decision aid (pDA) to support decision making in women considering immediate breast reconstruction. The primary aim of this study is to assess the impact of the pDA in reducing decisional conflict, and more generally, on the decision-making process and the decision quality. Additionally, we will investigate the pDA’s impact on health outcomes, explore predictors, and assess its cost-effectiveness. Methods A multicenter, two-armed randomized controlled trial (1:1) will be conducted. Women with breast cancer or ductal carcinoma in situ who will undergo a mastectomy and are eligible for immediate breast reconstruction will be invited to participate. The intervention group will receive access to the online pDA, whereas the control group will receive a widely available free information leaflet on breast reconstruction. Participants will complete online questionnaires at: baseline (T0), 1 week after consultation with a plastic surgeon (T1), and 3 (T2) and 12 months (T3) after surgery. The primary outcome is decisional conflict. Secondary outcomes include other measures reflecting the decision-making process and decision quality (e.g., decision regret), patient-reported health outcomes (e.g., satisfaction with the breasts) and costs. Discussion This study will provide evidence about the impact of an online pDA for women who will undergo mastectomy and are deciding about breast reconstruction. It will contribute to the knowledge on how to optimally support women in making this difficult decision. Trial registration This study is retrospectively registered at ClinicalTrials.gov ( NCT03791138 ).

A randomized, placebo-controlled treatment trial was conducted among 546 anemic (hemoglobin concentration, 7–11 g/dL) children aged 2–36 months in an area with intense malaria transmission in western Kenya. All children used bednets and received a single dose of sulfadoxine-pyrimethamine (SP) on enrollment, followed by either intermittent preventive treatment (IPT) with SP at 4 and 8 weeks and daily iron for 12 weeks, daily iron and IPT with SP placebo, IPT and daily iron placebo, or daily iron placebo and IPT with SP placebo (double placebo). The mean hemoglobin concentration at 12 weeks, compared with that for the double-placebo group, was 1.14 g/dL (95% confidence interval [CI], 0.82–1.47 g/dL) greater for the IPT+iron group, 0.79 g/dL (95% CI, 0.46–1.10 g/dL) greater for the iron group, and 0.17 g/dL (95% CI, −0.15–0.49 g/dL) greater for the IPT group. IPT reduced the incidence of malaria parasitemia and clinic visits, but iron did not. The combination of IPT and iron supplementation was most effective in the treatment of mild anemia. Although IPT prevented malaria, the hematological benefit it added to that of a single dose of SP and bednet use was modest

Deep brain stimulation is a treatment for Parkinson's disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target structures on routine clinical MR images, direct targeting of structures can be challenging. Non-clinical MR scanners with ultra-high magnetic field (7T or higher) have the potential to improve the quality of these images. This technology report provides an overview of the current possibilities of visualizing deep brain stimulation targets and their related structures with the aid of ultra-high field MRI. Reviewed studies showed improved resolution, contrast- and signal-to-noise ratios at ultra-high field. Sequences sensitive to magnetic susceptibility such as T2(*) and susceptibility weighted imaging and their maps in general showed the best visualization of target structures, including a separation between the subthalamic nucleus and the substantia nigra, the lamina pallidi medialis and lamina pallidi incompleta within the globus pallidus and substructures of the thalamus, including the ventral intermediate nucleus (Vim). This shows that the visibility, identification, and even subdivision of the small deep brain stimulation targets benefit from increased field strength. Although ultra-high field MR imaging is associated with increased risk of geometrical distortions, it has been shown that these distortions can be avoided or corrected to the extent where the effects are limited. The availability of ultra-high field MR scanners for humans seems to provide opportunities for a more accurate targeting for deep brain stimulation in patients with Parkinson's disease and related disorders.

Background Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. Methods Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-1 19kDa ) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children <5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001). Results A total of 12 MSP-1 19kDa haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P . falciparum were the most prevalent (range 32–37%), with an overall haplotype diversity of > 0.7. No MSP-1 19kDa 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points. Conclusion High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide information that could be useful in the design of future malaria vaccines for deployment in endemic areas with high ITN coverage and in interpretation of efficacy data for malaria vaccines based on 3D7 parasite strains.

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a \"jelly-roll\" fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure due to vasodilatation in pregnant animals suggest its therapeutic potential in preeclampsia.

Circulating tumor cells (CTCs) play an important role in metastasis formation. Aberrant signaling of oncogenic pathways (e.g., PI3K/AKT/mTOR pathway) drives tumor progression. In this work, the susceptibility of the colon cancer CTC‐derived cell line CTC‐MCC‐41 to AKT and mammalian target of rapamycin (mTOR) inhibitors was evaluated. Additionally, the functional role of the expressed AKT isoforms was characterized in this cell line. The efficacy of the AKT inhibitor MK2206, the mTOR inhibitor RAD001, and the combination was examined in CTC‐MCC‐41 cells in a murine intracardiac xenotransplantation model. Furthermore, stable isoform‐specific AKT1 or AKT2 knockdowns (KDs) as well as AKT1/AKT2 double‐KD cells were generated. Differentially regulated proteins and phospho‐peptides were identified using liquid chromatography coupled mass spectrometry (LC–MS). CTC‐MCC‐41 cells showed a high susceptibility for dual targeting of AKT and mTOR in vivo, indicating that selective eradication of CTCs by AKT/mTOR inhibitors may be considered a new treatment option in cancer. KD of AKT1 or AKT2 significantly reduced the proliferation of CTC‐MCC‐41 cells. AKT KDs share commonly regulated proteins and phospho‐proteins, but also regulate a large number uniquely. AKT1/AKT2 double‐KD cells show a strongly dysregulated replication machinery, as well as a decrease in cell cycle activity and stem‐cell‐associated processes, underlining the non‐redundant role of AKT isoforms. Dual targeting of AKT and mTOR using MK2206 and RAD001 reduces tumor burden in an intracardiac colon cancer circulating tumor cell xenotransplantation model. Analysis of AKT isoform‐specific knockdowns in CTC‐MCC‐41 reveals differentially regulated proteins and phospho‐proteins by liquid chromatography coupled mass spectrometry.