Was zu tun ist, damit Maschinen den Menschen dienen

Prozesse algorithmischer Entscheidungsfindung berühren in vielen Bereichen gesellschaftliche Teilhabe. Daraus ergeben sich Herausforderungen auf vier Feldern: 1. Gesellschaftliche Angemessenheit (Haben algorithmische Systeme sinnvolle Optimierungsziele?) 2. Überprüfen und erklären der Umsetzung (Verwirklichen algorithmische Systeme die sinnvollen Ziele?) 3. Schaffen von Diversität (Ist die Vielfalt der Systeme und Betreibermodelle groß genug, um gesellschaftlich angemessen zu sein?) 4. Übergreifende Rahmenbedingungen für teilhabeförderliche algorithmische Systeme (Genügen staatliche und individuelle Gestaltungskompetenzen dem gesellschaftlichen Anspruch?) Der Beitrag stellt eine Auswahl von Lösungsideen in allen vier skizzierten Handlungsfeldern vor. Die Auswahl ist nicht umfassend und abschließend. Sie veranschaulicht aber auch in dieser Form, dass Akteure aus allen drei Sektoren Möglichkeiten haben, algorithmische Entscheidungsfindung für mehr gesellschaftliche Teilhabe zu gestalten. Es gibt viele Ideen für Maßnahmen und Methoden bzgl. der gesellschaftlichen Gestaltung, Intervention und Kontrolle algorithmischer Entscheidungsfindung. Keineswegs scheint der Mensch der Maschine ausgeliefert

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Influence of Ocean Acidification on a Natural Winter-to-Summer Plankton Succession : First Insights from a Long-Term Mesocosm Study Draw Attention to Periods of Low Nutrient Concentrations

Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions. Five of the ten mesocosms were left unperturbed and served as controls (similar to 380 mu atm pCO(2)), whereas the others were enriched with CO2-saturated water to simulate realistic end-of-the-century carbonate chemistry conditions (mu 760 mu atm pCO(2)). We ran the experiment for 113 days which allowed us to study the influence of high CO2 on an entire winter-to-summer plankton succession and to investigate the potential of some plankton organisms for evolutionary adaptation to OA in their natural environment. This paper is the first in a PLOS collection and provides a detailed overview on the experimental design, important events, and the key complexities of such a "long-term mesocosm" approach. Furthermore, we analyzed whether simulated end-of-the-century carbonate chemistry conditions could lead to a significant restructuring of the plankton community in the course of the succession. At the level of detail analyzed in this overview paper we found that CO2-induced differences in plankton community composition were non-detectable during most of the succession except for a period where a phytoplankton bloom was fueled by remineralized nutrients. These results indicate: (1) Long-term studies with pelagic ecosystems are necessary to uncover OA-sensitive stages of succession. (2) Plankton communities fueled by regenerated nutrients may be more responsive to changing carbonate chemistry than those having access to high inorganic nutrient concentrations and may deserve particular attention in future studies.Peer reviewe

A Selective Screening Strategy Performed in Pre-School Children and Siblings to Detect Familial Hypercholesterolemia

(1) Background: Familial hypercholesterolemia (FH), a most common genetic disorder, is underdiagnosed and untreated, especially in children. Individuals with heterozygous familial hypercholesterolemia mostly present without clinical symptoms and are not informed about their high risk for myocardial infarction. Early diagnosis and treatment can prevent premature atherosclerosis and cardiovascular events in patients with FH. The aim was to evaluate the detection rate of pre-school children with FH at school doctor visits in Vienna and, moreover, to examine the frequency of FH identified in the children’s siblings by this type of screening. (2) Methods: The selective FH- screening was implemented at the school enrolment examinations in the public primary schools of Vienna. The study period included the school years starting in 2017 to 2020. FH was suspected if a questionnaire on hypercholesterolemia, or cardiovascular events in the family history or on the presence of xanthomas or xanthelasma, was positive. Subsequently, lipid testing was performed on pre-school children and their siblings and elevated lipid screening was defined as either positive by LDL-C ≥ 160 mg/dL and/or non-HDL-C ≥ 190 mg/dL or as borderline by LDL-C ≥ 130 mg/dL and/or non-HDL-C ≥ 160 mg/dL. (3) Results: 66,108 pre-school children participated in the school enrolment examination in 868 public elementary schools in Vienna. In 512 (4%) children, the questionnaire caused suspicion of FH. 344 families agreed their participation in the study. Out of 344 (52% male) tested pre-school children, 20 individuals (40% male) had elevated blood lipid levels with a mean LDL-C of 155 ± 29 mg/dL and a non-HDL-C of 180 ± 24 mg/dL. Out of 291 (44% male) tested siblings, 17 individuals (41% male) showed elevated lipids with a mean LDL-C of 144 ± 19 mg/dL, and a non-HDL-C of 174 ± 19 mg/dL. (4) Conclusions: Screening is the key for early diagnosis and treatment of FH. We have implemented a pre-school screening strategy in cooperation with school physicians. We could identify 20 pre-school children and 17 siblings with an elevated lipid screening test. Full implementation of FH-screening in the pre-school examination visits in Vienna would help to detect high-risk children

Relative Enhancement in Gadoxetate Disodium-Enhanced Liver MRI as an Imaging Biomarker in the Diagnosis of Non-Alcoholic Fatty Liver Disease in Pediatric Obesity

Relative enhancement (RE) in gadoxetate disodium (Gd-EOB-DTPA)-enhanced MRI is a reliable, non-invasive method for the evaluation and differentiation between simple steatosis and non-alcoholic steatohepatitis in adults. This study evaluated the diagnostic accuracy of RE in Gd-EOB-DTPA-enhanced liver MRI and hepatic fat fraction (HFF) in unenhanced liver MRI and ultrasound (US) for non-alcoholic fatty liver disease (NAFLD) screening in pediatric obesity. Seventy-four liver US and MRIs from 68 pediatric patients (13.07 ± 2.95 years) with obesity (BMI > BMI-for-age + 2SD) were reviewed with regard to imaging biomarkers (liver size, volume, echogenicity, HFF, and RE in Gd-EOB-DTPA-enhanced MRIs, and spleen size), blood biomarkers, and BMI. The agreement between the steatosis grade, according to HFF in MRI and the echogenicity in US, was moderate. Alanine aminotransferase correlated better with the imaging biomarkers in MRI than with those in US. BMI correlated better with liver size and volume on MRI than in US. In patients with RE < 1, blood biomarkers correlated better with RE than those in the whole sample, with a significant association between gamma-glutamyltransferase and RE (p = 0.033). In conclusion, the relative enhancement and hepatic fat fraction can be considered as non-invasive tools for the screening and follow-up of NAFLD in pediatric obesity, superior to echogenicity on ultrasound

Plasma Myostatin Increases with Age in Male Youth and Negatively Correlates with Vitamin D in Severe Pediatric Obesity

Obesity already causes non-communicable diseases during childhood, but the mechanisms of disease development are insufficiently understood. Myokines such as myostatin and irisin are muscle-derived factors possibly involved in obesity-associated diseases. This explorative study aims to investigate whether myostatin and irisin are associated with metabolic parameters, including the vitamin D status in pediatric patients with severe obesity. Clinical, anthropometric and laboratory data from 108 patients with severe obesity (>97th percentile) aged between 9 and 19 years were assessed. Myostatin, its antagonist follistatin, and irisin, were measured from plasma by ELISA. Myostatin concentrations, particularly in males, positively correlated with age and pubertal stage, as well as metabolic parameters such as insulin resistance. Irisin concentrations correlated positively with HDL and negatively with LDL cholesterol values. For follistatin, the associations with age and pubertal stage were inverse. Strikingly, a negative correlation of myostatin with serum vitamin D levels was observed that remained significant after adjusting for age and pubertal stage. In conclusion, there is an independent association of low vitamin D and elevated myostatin levels. Further research may focus on investigating means to prevent increased myostatin levels in interventional studies, which might open several venues to putative options to treat and prevent obesity-associated diseases

Vascular access for lipid apheresis: a challenge in young children with homozygous familial hypercholesterolemia

Background: Homozygous familial hypercholesterolemia (hoFH) is a rare genetic disorder leading to extremely increased LDL-cholesterol (LDL-C), resulting in high cardiovascular risk in early childhood. Lipid apheresis (LA) is an effective treatment and should be started as early as possible to prevent premature cardiovascular events. As peripheral punctures in children can be challenging due to small vessels and anxiety, this study aimed to evaluate feasibility and safety of central venous catheters (CVCs) as vascular access for LA in young children with hoFH. Methods: Retrospective analysis (2016-2019) on four children with hoFH aged 3-5 years, performing weekly or biweekly LA with a CVC. Results: LDL-C decreased by> 60%. In three children, the use of a permanent CVC for 698, 595, and 411 days, respectively, avoided difficult peripheral access, without the occurrence of occlusion or thrombosis. Unfortunately, one child had recurrent CVC-related infections and needed an arteriovenous fistula from the age of 5.Although the mean dwell time per catheter was 212 days, there were, as expected, severe side effects of early catheter infections with sepsis and accidental self-removal. Starting LA at an early age improved or stabilized carotid intima-media thickness (IMT) in three children. However, IMT did increase in one child caused by intolerance to peripheral punctures and LA interruption. Conclusions: Permanent CVCs are a viable temporary access choice for LA in young children with hoFH until peripheral venipuncture is practicable. The risk of CVC-related infections needs to be taken into account

Allogenic Fc Domain-Facilitated Uptake of IgG in Nasal Lamina Propria: Friend or Foe for Intranasal CNS Delivery?

Background: The use of therapeutic antibodies for the treatment of neurological diseases is of increasing interest. Nose-to-brain drug delivery is one strategy to bypass the blood brain barrier. The neonatal Fc receptor (FcRn) plays an important role in transepithelial transcytosis of immunoglobulin G (IgG). Recently, the presence of the FcRn was observed in nasal respiratory mucosa. The aim of the present study was to determine the presence of functional FcRn in olfactory mucosa and to evaluate its role in drug delivery. Methods: Immunoreactivity and messenger RNA (mRNA) expression of FcRn was determined in ex vivo porcine olfactory mucosa. Uptake of IgG was performed in a side-by-side cell and analysed by immunofluorescence. Results: FcRn was found in epithelial and basal cells of the olfactory epithelium as well as in glands, cavernous bodies and blood vessels. Allogenic porcine IgGs were found time-dependently in the lamina propria and along axonal bundles, while only small amounts of xenogenic human IgGs were detected. Interestingly, lymphoid follicles were spared from allogenic IgGs. Conclusion: Fc-mediated transport of IgG across the nasal epithelial barrier may have significant potential for intranasal delivery, but the relevance of immune interaction in lymphoid follicles must be clarified to avoid immunogenicity

Net sampling to assess the cephalopod biodiversity of Cabo Verde

Net catches of cephalopods were obtained during the cruises POS320/2 (March 2005), MSM49 (November/December 2015) and WH383 (March/April 2015) off Cabo Verde at a total of 18 stations at depths between 0 and 1000 m. Cephalopods were caught during POS320/2 with either a Isaacs-Kidd midwater trawl (IKMT) with a 6 m2 net opening, 4 mm mesh size equipped with a flowmeter, a Hydro-Bios Multinet Maxi with a 0.5 m2 net opening and 500 µm mesh size between the surface and 250 m water depth, or an 80 feet bottom trawl. Net sampling during MSM49 was conducted with two types of multiple opening/closing nets (MOCNESS) and an IKMT. The smaller MOCNESS had a net opening of 1 m2 opening (three nets with a mesh size of 2 mm and six nets with a mesh size of 335 μm) and the larger MOCNESS a net opening of 10 m2 opening (five nets, mesh size: 1.5 mm) and were deployed between the surface to 1000 m. The IKMT had a net opening of 7 m2 and ended in a cod end of 500 µm mesh size. It was deployed to a maximum depth of 500 m. During WH383 a pelagic trawl ('Aalnetz', Engel Netze, Bremerhaven, Germany) with a mouth opening of 16 x 30 m, length of 150 m including multiple opening-closing device, 260 meshes by 180 cm stretched mesh size at the front, a cod end 20 mm stretched mesh-opening and a 1.8 mm inlet sewn into last 1 m of cod end was used with a multisampler (Construction Services AS, Bergen, Norway) allowing depth-stratified sampling. During WH383 three strata (mean vertical extension of ca. 40 m) were trawled mostly during night and one time during daytime at depths between 30 and 700 m in horizontal tows for 30 minutes per stratum with a mean speed of three knots (2.8-3.3 kn). During this cruise, night trawls took place at 22:00 local time, and the day-time trawl at 12:00 local time. Onboard, cephalopods were identified morphologically to the lowest taxonomic level possible (species, genus or family), and whole specimens were preserved in formalin as voucher

In situ video observations to assess the cephalopod biodiversity of Cabo Verde

Pelagic video transects with the Pelagic In-Situ Observation System (PELAGIOS, (Hoving et al., 2019a)) were conducted during the cruises MSM49 (Christiansen et al., 2016) (transects between 30 and 1000 m, total towing duration > 80h), MSM61 (Fiedler et al., 2020) (transects between 80 and 1200 m, total hours of observations > 32h), POS520 (Hoving et al., 2018, p. 520) (transects between 30 and 2500 m, total hours of observations 27h), POS532 (Hoving et al., 2019b) (transects between 30 and 990 m, total hours of observations 19h) and M119 (Brandt, 2016) (transects between 50 and 700 m, total hours of observations > 20h) between 2015 and 2019 (Figure 1). PELAGIOS is a battery powered, high-definition camera system that is towed horizontally via a single-wired conductive sea-cable at 0.5 m s -1. Around 0.45 m2 of the water column in front of the camera is illuminated with an LED array. The attached depth sensor and/or a sensor for conductivity, temperature and depth (CTD) with oxygen sensor allows for hydrographic measurements and depth monitoring during transects. Pelagic video transects were conducted between 11-33 minutes per depth, towing the camera horizontally at specified depths. A deep-sea telemetry system allows for transmission of a low-resolution preview of the recorded video. During the cruises POS520 and POS532 the manned submersible JAGO (GEOMAR, Helmholtz Centre for Ocean Research) was used for 30 deployments of about four hours each between the surface and 350 m water depth. During the dives, video was recorded by a high-resolution camera. The videos taken during the PELAGIOS and JAGO dives were annotated manually using the Video Annotation and Reference System (VARS) developed at the Monterey Bay Aquarium Research Institute, which allows annotation and congruent collection of video frames. We also provide raw data on environmental DNA samples taken during POS532 in February 2019 at five stations. The stations off the islands Santo Antão and Fogo were close to the coast (maximum sampled depth 2500 m), CVOO was a reference station in the open ocean (maximum sampled depth 3000 m) and the stations Cyclone and Anticyclone were located eddies that had formed in the wake of Fogo and had propagated southwards (maximum sampled depths 2200 and 600 m, respectively). Per sampled depth, three biological replicates of two liters of seawater each were collected from three different 10 liter Niskin bottles mounted on a CTD rosette. For filtration, 0.22 µm pore size Sterivex-GP filter (Merck Millipore) were directly connected to the Niskin bottle with sterile tubing. The weight of the water in the Niskin bottles was sufficient to filter two liters of seawater per filter. The filters were closed with sterile plastic caps and stored at -80°C until further processing in the laboratory