Production of Inflected Novel Words in Older Adults With and Without Dementia

While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish‐conforming pseudo‐words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer's disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants' inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single‐route models) and contradict theories advocating for formal symbolic rules (dual‐route models).While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish-conforming pseudo-words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer’s disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants’ inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single-route models) and contradict theories advocating for formal symbolic rules (dual-route models).Peer reviewe

Osteoprotegerin, soluble receptor activator nuclear factor-κB ligand, nuclear factor kappa B and intestinal trefoil factor 3 are promising biomarkers in diagnosis and follow- up inflammatory bowel disease patients

Background: Inflammatory bowel disease (IBD) is a condition in which the gastrointestinal system becomes inflamed for no apparent reason. Its incidence increased during the last few decades. As a result, it's critical to understand how to validate a clinical diagnosis and monitor any progress using a simple procedure. Osteoprotegerin (OPG), which interacts with RANKL, regulates RANK/RANKL signaling. OPG is a decoy receptor for soluble receptor activator of nuclear factor-B ligand (sRANKL), which stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the healing trefoil factor 3 (TFF3), which could be employed as in the diagnosis and follow-up of IBD patients, biomarkers are used. Objectives: The aim of the current work was to evaluate the role of RANKL (sRANKL), OPG, NF-κB , and TFF3 in in the diagnosis of active IBD. Subjects and methods: Thirty-five newly diagnosed untreated IBD patients and thirty-five healthy controls were included in this study. Patients were then given particular treatment either in the form of cortisone, mesalamin, immunotherapy or infliximab and immunotherapy for 3 months and attend for second visit. OPG, sRANKL, NF-κB and TFF3 levels were estimated by ELISA method using commercial kits in patients before and after treatment and healthy control. Results: Patients with IBD had significantly increased levels of OPG, sRANKL, NF-B, and TFF3 than healthy controls (P =0.0001). After 3 months of treatment, patients' levels of NF-B and TFF3 were significantly lower (p = 0.0001 and 0.03, respectively). Conclusion: The biomarkers OPG, sRANKL, NF-κB , and TFF3 show promise in the diagnosis of active IBD. The decrease in NF-κB and TFF3 following treatment suggests that be used as biomarkers to track disease activity and treatment effectiveness

The acute mania of King George III: A computational linguistic analysis.

We used a computational linguistic approach, exploiting machine learning techniques, to examine the letters written by King George III during mentally healthy and apparently mentally ill periods of his life. The aims of the study were: first, to establish the existence of alterations in the King's written language at the onset of his first manic episode; and secondly to identify salient sources of variation contributing to the changes. Effects on language were sought in two control conditions (politically stressful vs. politically tranquil periods and seasonal variation). We found clear differences in the letter corpus, across a range of different features, in association with the onset of mental derangement, which were driven by a combination of linguistic and information theory features that appeared to be specific to the contrast between acute mania and mental stability. The paucity of existing data relevant to changes in written language in the presence of acute mania suggests that lexical, syntactic and stylometric descriptions of written discourse produced by a cohort of patients with a diagnosis of acute mania will be necessary to support the diagnosis independently and to look for other periods of mental illness of the course of the King's life, and in other historically significant figures with similarly large archives of handwritten documents

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030