The lexicographic treatment of the demonstrative copulative in Sesotho sa Leboa — an exercise in multiple cross-referencing

In this research article an in-depth investigation is presented of the lexicographic treatment of the demonstrative copulative (DC) in Sesotho sa Leboa. This one case study serves as an example to illustrate the so-called 'paradigmatic lemmatisation' of closed-class words in the African languages. The need for such an approach follows a discussion, in Sections 1 and 2 respectively, of the present and missing directions in African-language metalexicography. A theoretical conspectus of the DC in Sesotho sa Leboa is then offered in Section 3, while Section 4 examines the treatment of the DC in the four existing desktop dictionaries for this language. The outcomes from the two latter sections are then used in Section 5, which analyses the problems of and options for a sound lexicographic treatment of the DC in bilingual and monolingual dictionaries. The next two sections proceed with a review of the practical implementation of the DC lemmatisation suggestions in PyaSsaL, i.e. the Pukuntšutlhaloši ya Sesotho sa Leboa 'Explanatory Sesotho sa Leboa Dictionary' — with Section 6 focussing on the hardcopy and Section 7 on the online version. In the process, the very first fully monolingual African-language dictionary on the Internet is introduced. Section 8, finally, concludes briefly. Keywords: lexicography, paradigmatic lemmatisation, african languages, sesotho sa leboa (northern sotho, sepedi), demonstrative copulative, cross-referencing, corpus, monolingual dictionary, bilingual dictionar

From junior to senior Pinocchio: A cross-sectional lifespan investigation of deception

We present the first study to map deception across the entire lifespan. Specifically, we investigated age-related difference in lying proficiency and lying frequency. A large community sample (n = 1005) aged between 6 and 77 were surveyed on their lying frequency, and performed a reaction-time (RT) based deception task to assess their lying proficiency. Consistent with the inverted U-shaped pattern of age-related changes in inhibitory control that we observed in a stop signal task, we found that lying proficiency improved during childhood (in accuracy, not RTs), excelled in young adulthood (in accuracy and RTs), and worsened throughout adulthood (in accuracy and RTs). Likewise, lying frequency increased in childhood, peaked in adolescence, and decreased during adulthood. In sum, we observed important age-related difference in deception that generally fit with the U-shaped pattern of age-related changes observed in inhibitory control. Theoretical and practical implications are discussed from a cognitive view of deception

Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes

Syndromic primary immunodeficiencies are rare genetic disorders that affect both the immune system and other organ systems. More often, the immune defect is not the major clinical problem and is sometimes only recognized after a diagnosis has been made based on extra-immunological abnormalities. Here, we report two sibling pairs with syndromic primary immunodeficiencies that exceptionally presented with a phenotype resembling early-onset common variable immunodeficiency, while extra-immunological characteristics were not apparent at that time. Additional features not typically associated with common variable immunodeficiency were diagnosed only later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed KMT2-Aassociated Wiedemann-Steiner syndrome in one sibling pair and their mother. In the other sibling pair, targeted testing of the known disease gene for Roifman syndrome (RNU4ATAC) provided a definite diagnosis. With this study, we underline the importance of an early-stage and thorough genetic assessment in paediatric patients with a common variable immunodeficiency phenotype, to establish a conclusive diagnosis and guide patient management. In addition, this study extends the mutational and immunophenotypical spectrum of Wiedemann-Steiner and Roifman syndromes and highlights potential directions for future pathophysiological research

Lipid homeostasis and inflammatory activation are disturbed in classically activated macrophages with peroxisomal β-oxidation deficiency

Macrophage activation is characterized by pronounced metabolic adaptation. Classically activated macrophages show decreased rates of mitochondrial fatty acid oxidation and oxidative phosphorylation and acquire a glycolytic state together with their pro-inflammatory phenotype. In contrast, alternatively activated macrophages require oxidative phosphorylation and mitochondrial fatty acid oxidation for their anti-inflammatoryfunction. Although it is evident that mitochondrial metabolism is regulated during macrophage polarization and essential for macrophagefunction, little is known on the regulation and role of peroxisomal -oxidation during macrophage activation. In this study, we show that peroxisomal -oxidation is strongly decreased in classically activated bone-marrow-derived macrophages (BMDM) and mildly induced in alternatively activated BMDM. To examine the role of peroxisomal -oxidation in macrophages, we used Mfp2(-/-) BMDM lacking the key enzyme of this pathway. Impairment of peroxisomal -oxidation in Mfp2(-/-) BMDM did not cause lipid accumulation but rather an altered distribution of lipid species with very-long-chain fatty acids accumulating in the triglyceride and phospholipid fraction. These lipid alterations in Mfp2(-/-) macrophages led to decreased inflammatory activation of Mfp2(-/-) BMDM and peritoneal macrophages evidenced by impaired production of several inflammatory cytokines and chemokines, but did not affect anti-inflammatory polarization. The disturbed inflammatory responses of Mfp2(-/-) macrophages did not affect immune cell infiltration, as mice with selective elimination of MFP2 from myeloid cells showed normal monocyte and neutrophil influx upon challenge with zymosan. Together, these data demonstrate that peroxisomal -oxidation is involved in fine-tuning the phenotype of macrophages, probably by influencing the dynamic lipid profile during macrophage polarization

Correctly validating results from single molecule data: the case of stretched exponential decay in the catalytic activity of single lipase B molecules

The question of how to validate and interpret correctly the waiting time probability density functions (WT-PDFs) from single molecule data is addressed. It is shown by simulation that when a stretched exponential WT-PDF, with a stretched exponent alfa and a time scale parameter tau, generates the off periods of a two-state trajectory, a reliable recovery of the input WT-PDF from the trajectory is obtained even when the bin size used to define the trajectory, dt, is much larger than the parameter tau. This holds true as long as the first moment of the WT-PDF is much larger than dt. Our results validate the results in an earlier study of the activity of single Lipase B molecules and disprove recent related critique

Genetic and environmental susceptibility to food allergy in a registry of twins

Non peer reviewe

Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain Suffering from Opioid-Induced Constipation

Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC. A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of a parts per thousand yen1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with a parts per thousand yen3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored. More patients had an increase from baseline of a parts per thousand yen1 SCBM per week (weeks 1-4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1-4, more patients in the prucalopride groups achieved an average of a parts per thousand yen3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters. In this population with OIC, prucalopride improved bowel function and was safe and well tolerated

Poly-β-hydroxybutyrate administration during early life: effects on performance, immunity and microbial community of European sea bass yolk-sac larvae

The reliable production of marine fish larvae is one of the major bottlenecks in aquaculture due to high mortalities mainly caused by infectious diseases. To evaluate if the compound poly-β-hydroxybutyrate (PHB) might be a suitable immunoprophylactic measure in fish larviculture, its capacity to improve immunity and performance in European sea bass (Dicentrarchus labrax) yolk-sac larvae was explored. PHB was applied from mouth opening onwards to stimulate the developing larval immune system at the earliest possible point in time. Larval survival, growth, microbiota composition, gene expression profiles and disease resistance were assessed. PHB administration improved larval survival and, furthermore, altered the larva-associated microbiota composition. The bacterial challenge test using pathogenic Vibrio anguillarum revealed that the larval disease resistance was not influenced by PHB. The expression profiles of 26 genes involved e.g. in the immune response showed that PHB affected the expression of the antimicrobial peptides ferritin (fer) and dicentracin (dic), however, the response to PHB was inconsistent and weaker than previously demonstrated for sea bass post-larvae. Hence, the present study highlights the need for more research focusing on the immunostimulation of different early developmental stages for gaining a more comprehensive picture and advancing a sustainable production of high quality fry

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015