Undecidability of Equality for Codata Types

International audienceDecidability of type checking for dependently typed languages usually requires a decidable equality on types. Since bisimilarity on (weakly final) coalgebras such as streams is undecidable, one cannot use it as the equality in type checking. Instead, languages based on dependent types with decidable type checking such as Coq or Agda use intensional equality for type checking. Two streams are definitionally equal if the underlying terms reduce to the same normal form, i.e. if the underlying programs are syntactically equivalent. For reasoning about equality of streams one introduces bisimilarity as a propositional rather than judgemental equality.In this paper we show that it is not possible to strengthen intensional equality in a decidable way while having the property that equality respects one step expansion, which means that a stream with head n and tail s is equal to $\mathrm {cons}(n,s)$ cons(n,s). This property, which would be very useful in type checking, would not necessarily imply that bisimilar streams are equal, and we prove that there exist equalities with this properties which do not coincide with bisimilarity. Whereas a proof that bisimilarity on streams is undecidable is straightforward, proving that respecting one step expansion makes equality undecidable is much more involved and relies on an inseparability result for sets of codes for Turing machines. We prove this theorem both for streams with primitive corecursion and with coiteration as introduction rule.Therefore, pattern matching on streams is, understood literally, not a valid principle, since it assumes that every stream is equal to a stream of the form $\mathrm {cons}(n,s)$ cons(n,s). We relate this problem to the subject reduction problem found when adding pattern matching on coalgebras to Coq and Agda. We discuss how this was solved in Agda by defining coalgebras by their elimination rule and replacing pattern matching on coalgebras by copattern matching, and how this relates to the approach in Agda which uses the type of delayed computations, i.e. the so called “musical notation” for codata types

Applications of Non-invasive Neuromodulation for the Management of Disorders Related to COVID-19

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19. Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders. Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders. Results: Non-invasive neuromodulationmaymanage disorders associated with COVID- 19 through four pathways: (1) Direct infection mitigation through the stimulation of regions involved in the regulation of systemic anti-inflammatory responses and/or autonomic responses and prevention of neuroinflammation and recovery of respiration; (2) Amelioration of COVID-19 symptoms of musculoskeletal pain and systemic fatigue; (3) Augmenting cognitive and physical rehabilitation following critical illness; and (4) Treating outbreak-relatedmental distress including neurological and psychiatric disorders exacerbated by surrounding psychosocial stressors related to COVID-19. The selection of the appropriate techniques will depend on the identified target treatment pathway. Conclusion: COVID-19 infection results in a myriad of acute and chronic symptoms, both directly associated with respiratory distress (e.g., rehabilitation) or of yet-tobe- determined etiology (e.g., fatigue). Non-invasive neuromodulation is a toolbox of techniques that based on targeted pathways and empirical evidence (largely in non- COVID-19 patients) can be investigated in the management of patients with COVID-19

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

Sarcomatoid Change in Intrahepatic Cholangiocarcinoma

Sarcomatoid transformation is a rare but well documented change that may occur in intrahepatic cholangiocarcinomas. We report a tumor of this type to illustrate the difficulties in properly diagnosing cholangiocarcinoma when only the sarcomatous component is sampled by transcutaneous needle biopsy. The proper diagnosis of the tumor was suggested by finding the expression of cytokeratin 7 in the sarcomatous spindle cells. The surgically resected tumor comprised a spindle cell sarcomatous and an adenocarcinomatous component accounting for approximately 30% and 70% of the total tumor mass respectively

Sarcomatoid change in intrahepatic cholangiocarcinoma

Sarcomatoid transformation is a rare but well documented change that may occur in intrahepatic cholangiocarcinomas. We report a tumor of this type to illustrate the difficulties in properly diagnosing cholangiocarcinoma when only the sarcomatous component is sampled by transcutaneous needle biopsy. The proper diagnosis of the tumor was suggested by finding the expression of cytokeratin 7 in the sarcomatous spindle cells. The surgically resected tumor comprised a spindle cell sarcomatous and an adenocarcinomatous component accounting for approximately 30% and 70% of the total tumor mass respectivel

In vivo Anti-diarrheal and CNS Depressant Activities of Hemigraphis hirta (Vahl) T. Anders.

Hemigraphis hirta has been used by folk practitioners to alleviate symptoms of several diseases, although the pharmacological activities of this plant have not been thoroughly explored. The current study was designed to assess the anti-diarrheal and CNS depressant activities of H. hirta in mice model. For both assays, the experimental mice received the methanolic crude extract and its petroleum ether soluble fraction at dose of 200 and 400 mg/kg body weight which are denoted as CME 200, CME 400, PESF 200 and PESF 400, respectively. Both fractions remarkably attenuated castor oil-induced diarrheal effect in a dose-dependent manner and the results were comparable to standard loperamide (89.47%). Among all, PESF 400 exhibited statistically significant (p &lt; 0.01) anti-diarrheal activity as demonstrated by 78.95% inhibition of defacetion. Compared to reference drug diazepam, all the tested samples considerably shortened the time for onset of sleep and prolonged the duration of phenobarbitoneinduced sleep in mice. The results of our present study, being reported for the first time, demonstrate that the methanol extract of leaves of H. hirta and its organic soluble partionates possesses significant anti-diarrheal and CNS depressant properties. However, this preliminary screening requires further detailed investigation to confirm these findings as well as to isolate and characterize the bioactive compounds.&#x0D; Bangladesh Pharmaceutical Journal 22(2): 176-180, 2019</jats:p