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There are special challenges in implementing parenteral nutrition (PN) in paediatric patients, which arises from the wide range of patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg, and their varying substrate requirements. Age and maturity-related changes of the metabolism and fluid and nutrient requirements must be taken into consideration along with the clinical situation during which PN is applied. The indication, the procedure as well as the intake of fluid and substrates are very different to that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy needs of premature infants and newborns per kg body weight are markedly higher than of older paediatric and adult patients. Premature infants <35 weeks of pregnancy and most sick term infants usually require full or partial PN. In neonates the actual amount of PN administered must be calculated (not estimated). Enteral nutrition should be gradually introduced and should replace PN as quickly as possible in order to minimise any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. If energy and nutrient demands in children and adolescents cannot be met through enteral nutrition, partial or total PN should be considered within 7 days or less depending on the nutritional state and clinical conditions.
Systematic reviews represent the core and backbone of evidence-based medicine (EBM) strategies in all fields of medicine. In order to depict a first global sketch of the international efforts in the Cochrane database systematic reviews (CDSR), we analyzed the systematic reviews of the Cochrane database. Our global maps of systematic reviewing offer intriguing structural insights into the world of EBM strategies. They demonstrate that for the CDSR, the UK and Commonwealth countries take the lead position. Since patients, care providers and health systems all over the world benefit from systematic reviewing, institutions in other countries should increase their commitment.
Using experimental data from a comprehensive field study, we explore the causal effects of algorithmic discrimination on economic efficiency and social welfare. We harness economic, game-theoretic, and state-of-the-art machine learning concepts allowing us to overcome the central challenge of missing counterfactuals, which generally impedes assessing economic downstream consequences of algorithmic discrimination. This way, we are able to precisely quantify downstream efficiency and welfare ramifications, which provides us a unique opportunity to assess whether the introduction of an AI system is actually desirable. Our results highlight that AI systems’ capabilities in enhancing welfare critically depends on the degree of inherent algorithmic biases. While an unbiased system in our setting outperforms humans and creates substantial welfare gains, the positive impact steadily decreases and ultimately reverses the more biased an AI system becomes. We show that this relation is particularly concerning in selective-labels environments, i.e., settings where outcomes are only observed if decision-makers take a particular action so that the data is selectively labeled, because commonly used technical performance metrics like the precision measure are prone to be deceptive. Finally, our results depict that continued learning, by creating feedback loops, can remedy algorithmic discrimination and associated negative effects over time.
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a "selfie" altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app "Smokerface" (=mixed − methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18–40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2–3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students
Serum levels of the lipid mediator sphingosine-1-phosphate (S1P) are reduced in septic patients and are inversely associated with disease severity. We show that serum S1P is reduced in human sepsis and in murine models of sepsis. We then investigated whether pharmacological or genetic approaches that alter serum S1P may attenuate cardiac dysfunction and whether S1P signaling might serve as a novel theragnostic tool in sepsis. Mice were challenged with lipopolysaccharide and peptidoglycan (LPS/PepG). LPS/PepG resulted in an impaired systolic contractility and reduced serum S1P. Administration of the immunomodulator FTY720 increased serum S1P, improved impaired systolic contractility and activated the phosphoinositide 3-kinase (PI3K)-pathway in the heart. Cardioprotective effects of FTY720 were abolished following administration of a S1P receptor 2 (S1P2) antagonist or a PI3K inhibitor. Sphingosine kinase-2 deficient mice had higher endogenous S1P levels and the LPS/PepG-induced impaired systolic contractility was attenuated in comparison with wild-type mice. Cardioprotective effects of FTY720 were confirmed in polymicrobial sepsis. We show here for the first time that the impaired left ventricular systolic contractility in experimental sepsis is attenuated by FTY720. Mechanistically, our results indicate that activation of S1P2 by increased serum S1P and the subsequent activation of the PI3K-Akt survival pathway significantly contributes to the observed cardioprotective effect of FTY720.
In current discussions on large language models (LLMs) such as GPT, understanding their ability to emulate facets of human intelligence stands central. Using behavioral economic paradigms and structural models, we investigate GPT’s cooperativeness in human interactions and assess its rational goal-oriented behavior. We discover that GPT cooperates more than humans and has overly optimistic expectations about human cooperation. Intriguingly, additional analyses reveal that GPT’s behavior isn’t random; it displays a level of goal-oriented rationality surpassing human counterparts. Our findings suggest that GPT hyper-rationally aims to maximize social welfare, coupled with a strive of self-preservation. Methodologically, our esearch highlights how structural models, typically employed to decipher human behavior, can illuminate the rationality and goal-orientation of LLMs. This opens a compelling path for future research into the intricate rationality of sophisticated, yet enigmatic artificial agents.
In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.
In the upcoming years, the internet of things (IoT)will enrich daily life. The combination of artificial intelligence(AI) and highly interoperable systems will bring context-sensitive multi-domain services to reality. This paper describesa concept for an AI-based smart living platform with open-HAB, a smart home middleware, and Web of Things (WoT) askey components of our approach. The platform concept con-siders different stakeholders, i.e. the housing industry, serviceproviders, and tenants. These activities are part of the Fore-Sight project, an AI-driven, context-sensitive smart living plat-form.
Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus. Translation of these findings would benefit from evidence of efficacy in non-status epilepticus models and validation in another species. Here, we report that electrographic seizures and convulsive behavior are strongly reduced in adult mice pre-treated with Ant-134 in the pentylenetetrazol model. Pre-treatment with Ant-134 did not affect the severity of status epilepticus induced by perforant pathway stimulation in adult rats, a toxin-free model of acquired epilepsy. Nevertheless, Ant-134 post-treatment reduced the number of rats developing spontaneous seizures by 86% in the perforant pathway stimulation model and Ant-134 delayed epileptiform activity in a rat ex vivo hippocampal slice model. The potent anticonvulsant effects of Ant-134 in multiple models may encourage pre-clinical development of this approach to epilepsy therapy.
The formation of secondary particles in the atmosphere accounts for more than half of global cloud condensation nuclei. Experiments at the CERN CLOUD (Cosmics Leaving OUtdoor Droplets) chamber have underlined the importance of ions for new particle formation, but quantifying their effect in the atmosphere remains challenging. By using a novel instrument setup consisting of two nano-particle counters, one of them equipped with an ion filter, we were able to further investigate the ion-related mechanisms of new particle formation. In autumn 2015, we carried out experiments at CLOUD on four systems of different chemical compositions involving monoterpenes, sulfuric acid, nitrogen oxides, and ammonia. We measured the influence of ions on the nucleation rates under precisely controlled and atmospherically relevant conditions. Our results indicate that ions enhance the nucleation process when the charge is necessary to stabilize newly formed clusters, i.e. in conditions where neutral clusters are unstable. For charged clusters that were formed by ion-induced nucleation, we were able to measure, for the first time, their progressive neutralization due to recombination with oppositely charged ions. A large fraction of the clusters carried a charge at 1.2 nm diameter. However, depending on particle growth rates and ion concentrations, charged clusters were largely neutralized by ion–ion recombination before they grew to 2.2 nm. At this size, more than 90 % of particles were neutral. In other words, particles may originate from ion-induced nucleation, although they are neutral upon detection at diameters larger than 2.2 nm. Observations at Hyytiälä, Finland, showed lower ion concentrations and a lower contribution of ion-induced nucleation than measured at CLOUD under similar conditions. Although this can be partly explained by the observation that ion-induced fractions decrease towards lower ion concentrations, further investigations are needed to resolve the origin of the discrepancy.