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

Spatiotemporal Patterns of Menin Localization in Developing Murine Brain: Co-Expression with the Elements of Cholinergic Synaptic Machinery

Menin, a product of MEN1 (multiple endocrine neoplasia type 1) gene is an important regulator of tissue development and maintenance; its perturbation results in multiple tumors—primarily of the endocrine tissue. Despite its abundance in the developing central nervous system (CNS), our understanding of menin’s role remains limited. Recently, we discovered menin to play an important role in cholinergic synaptogenesis in the CNS, whereas others have shown its involvement in learning, memory, depression and apoptosis. For menin to play these important roles in the CNS, its expression patterns must be corroborated with other components of the synaptic machinery imbedded in the learning and memory centers; this, however, remains to be established. Here, we report on the spatio-temporal expression patterns of menin, which we found to exhibit dynamic distribution in the murine brain from early development, postnatal period to a fully-grown adult mouse brain. We demonstrate here that menin expression is initially widespread in the brain during early embryonic stages, albeit with lower intensity, as determined by immunohistochemistry and gene expression. With the progression of development, however, menin expression became highly localized to learning, memory and cognition centers in the CNS. In addition to menin expression patterns throughout development, we provide the first direct evidence for its co-expression with nicotinic acetylcholine, glutamate and GABA (gamma aminobutyric acid) receptors—concomitant with the expression of both postsynaptic (postsynaptic density protein PSD-95) and presynaptic (synaptotagamin) proteins. This study is thus the first to provide detailed analysis of spatio-temporal patterns of menin expression from initial CNS development to adulthood. When taken together with previously published studies, our data underscore menin’s importance in the cholinergic neuronal network assembly underlying learning, memory and cognition

Phytosterol-Loaded Surface-Tailored Bioactive-Polymer Nanoparticles for Cancer Treatment: Optimization, In Vitro Cell Viability, Antioxidant Activity, and Stability Studies

This study aimsto optimize, characterize, and assess the phytosterol-loaded surface-tailored bioactive Alginate/Chitosan NPs for antitumor efficacy against breast cancer. β-Sitosterol-loaded Alginate/Chitosan nanoparticles (β-SIT-Alg/Ch-NPs) were fabricated using an ion-gelation technique, and then the NPs’ surfaces were activated using an EDC/sulfo-NHS conjugation reaction. The activated chitosan NPs werefunctionalized with folic acid (FA), leveled as β-SIT-Alg/Ch-NPs-FA. Moreover, the functionalized NPs were characterized for size distribution, polydispersity index (PDI), and surface charge, FT-IR and DSC. β-SIT released from β-SIT-Alg/Ch-NPs was estimated in various biorelevant media of pH 7.4, 6.5, and 5.5, and data werefitted into various kinetic models. The cytotoxic study of β-SIT-Alg/Ch-NPs-FA against the cancer cell line was established. The antioxidant study of developed β-SIT-Alg/Ch-NPs was performed using DPPH assay. The stability of developed optimized formulation was assessed in phosphate buffer saline (PBS, pH 7.4), as per ICH guidelines. The drug-entrapped Alg/Ch-NPs-FA appeared uniform and nonaggregated, and the nanoscale particle measured a mean size of 126 ± 8.70 nm. The %drug encapsulation efficiency and %drug loading in β-SIT-Alg/Ch-NPs-FA were 91.06 ± 2.6% and 6.0 ± 0.52%, respectively. The surface charge on β-SIT-Alg/Ch-NPs-FA was measured as +25 mV. The maximum β-SIT release from β-SIT-Alg/Ch-NPs-FA was 71.50 ± 6.5% in pH 5.5. The cytotoxic assay expressed an extremely significant antitumor effect by β-SIT-Alg/Ch-NPs-FA when compared to β-SIT-suspension (p p > 0.05) in particle sizes and other parameters under study in the specific period

Phytosterol-Loaded Surface-Tailored Bioactive-Polymer Nanoparticles for Cancer Treatment: Optimization, In Vitro Cell Viability, Antioxidant Activity, and Stability Studies

This study aimsto optimize, characterize, and assess the phytosterol-loaded surface-tailored bioactive Alginate/Chitosan NPs for antitumor efficacy against breast cancer. &beta;-Sitosterol-loaded Alginate/Chitosan nanoparticles (&beta;-SIT-Alg/Ch-NPs) were fabricated using an ion-gelation technique, and then the NPs&rsquo; surfaces were activated using an EDC/sulfo-NHS conjugation reaction. The activated chitosan NPs werefunctionalized with folic acid (FA), leveled as &beta;-SIT-Alg/Ch-NPs-FA. Moreover, the functionalized NPs were characterized for size distribution, polydispersity index (PDI), and surface charge, FT-IR and DSC. &beta;-SIT released from &beta;-SIT-Alg/Ch-NPs was estimated in various biorelevant media of pH 7.4, 6.5, and 5.5, and data werefitted into various kinetic models. The cytotoxic study of &beta;-SIT-Alg/Ch-NPs-FA against the cancer cell line was established. The antioxidant study of developed &beta;-SIT-Alg/Ch-NPs was performed using DPPH assay. The stability of developed optimized formulation was assessed in phosphate buffer saline (PBS, pH 7.4), as per ICH guidelines. The drug-entrapped Alg/Ch-NPs-FA appeared uniform and nonaggregated, and the nanoscale particle measured a mean size of 126 &plusmn; 8.70 nm. The %drug encapsulation efficiency and %drug loading in &beta;-SIT-Alg/Ch-NPs-FA were 91.06 &plusmn; 2.6% and 6.0 &plusmn; 0.52%, respectively. The surface charge on &beta;-SIT-Alg/Ch-NPs-FA was measured as +25 mV. The maximum &beta;-SIT release from &beta;-SIT-Alg/Ch-NPs-FA was 71.50 &plusmn; 6.5% in pH 5.5. The cytotoxic assay expressed an extremely significant antitumor effect by &beta;-SIT-Alg/Ch-NPs-FA when compared to &beta;-SIT-suspension (p &lt; 0.001). The antioxidant capacity of &beta;-SIT-Alg/Ch-NPs-FA was 91 &plusmn; 5.99% compared to 29 &plusmn; 8.02% for &beta;-SIT-suspension. The stability of NPs noticed an unworthy alteration (p &gt; 0.05) in particle sizes and other parameters under study in the specific period

Factors from Human Embryonic Stem Cell-derived Fibroblast-like Cells Promote Topology-dependent Hepatic Differentiation in Primate Embryonic and Induced Pluripotent Stem Cells*

The future clinical use of embryonic stem cell (ESC)-based hepatocyte replacement therapy depends on the development of an efficient procedure for differentiation of hepatocytes from ESCs. Here we report that a high density of human ESC-derived fibroblast-like cells (hESdFs) supported the efficient generation of hepatocyte-like cells with functional and mature hepatic phenotypes from primate ESCs and human induced pluripotent stem cells. Molecular and immunocytochemistry analyses revealed that hESdFs caused a rapid loss of pluripotency and induced a sequential endoderm-to-hepatocyte differentiation in the central area of ESC colonies. Knockdown experiments demonstrated that pluripotent stem cells were directed toward endodermal and hepatic lineages by FGF2 and activin A secreted from hESdFs. Furthermore, we found that the central region of ESC colonies was essential for the hepatic endoderm-specific differentiation, because its removal caused a complete disruption of endodermal differentiation. In conclusion, we describe a novel in vitro differentiation model and show that hESdF-secreted factors act in concert with regional features of ESC colonies to induce robust hepatic endoderm differentiation in primate pluripotent stem cells

University of Calgary - Zoology 435 Insect Survey Report

Students enrolled in Zoology 435 – Entomology, during fall term 2020 conducted a biodiversity survey of insects in the City of Calgary and their backyards in a variety of localities. Students collected insects where permits and permissions were available, and took digital observations for the iNaturalist platform from all localities

Measurement of inclusive and differential cross sections for W+^{+}W−^{-} production in proton-proton collisions at s= \sqrt{s} = 13.6 TeV

Measurements at $\sqrt{s}=$ 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb$^{-1}$. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavour and charge of the leptons, the number of jets, and number of jets originating from b quarks. An inclusive W$^{+}$W$^{-}$ production cross section of 125.7 $\pm$ 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For first time in proton-proton collisions, WW events with at least two reconstructed jets are studied and compared with recent theoretical predictions.Measurements at $\sqrt{s}$ = 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb$^{-1}$. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavour and charge of the leptons, the number of jets, and number of jets originating from b quarks. An inclusive W$^+$W$^-$ production cross section of 125.7 $\pm$ 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For first time in proton-proton collisions, WW events with at least two reconstructed jets are studied and compared with recent theoretical predictions

Observation of the J/ψ\psi →\to μ+μ−μ+μ−\mu^+\mu^-\mu^+\mu^- decay in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe J/$\psi$$\to$$\mu^+\mu^-\mu^+\mu^-$ decay has been observed with a statistical significance in excess of five standard deviations. The analysis is based on an event sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 33.6 fb${-1}$. Normalizing to the J/$\psi$$\to$$\mu^+\mu^-$ decay mode leads to a branching fraction [10.1$^{+3.3}_{-2.7}$ (stat) $\pm$ 0.4 (syst) ]$\times$ 10$^{-7}$, a value that is consistent with the standard model prediction

Enriching the physics program of the CMS experiment via data scouting and data parking

International audienceSpecialized data-taking and data-processing techniques were introduced by the CMS experiment in Run 1 of the CERN LHC to enhance the sensitivity of searches for new physics and the precision of standard model measurements. These techniques, termed data scouting and data parking, extend the data-taking capabilities of CMS beyond the original design specifications. The novel data-scouting strategy trades complete event information for higher event rates, while keeping the data bandwidth within limits. Data parking involves storing a large amount of raw detector data collected by algorithms with low trigger thresholds to be processed when sufficient computational power is available to handle such data. The research program of the CMS Collaboration is greatly expanded with these techniques. The implementation, performance, and physics results obtained with data scouting and data parking in CMS over the last decade are discussed in this Report, along with new developments aimed at further improving low-mass physics sensitivity over the next years of data taking

Observation of the J/ψ\psi→\toμ+μ−μ+μ−\mu^+\mu^-\mu^+\mu^- decay in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe J/$\psi$$\to$$\mu^+\mu^-\mu^+\mu^-$ decay has been observed with a statistical significance in excess of five standard deviations. The analysis is based on an event sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 33.6 fb${-1}$. Normalizing to the J/$\psi$$\to$$\mu^+\mu^-$ decay mode leads to a branching fraction [10.1$^{+3.3}_{-2.7}$ (stat) $\pm$ 0.4 (syst) ]$\times$ 10$^{-7}$, a value that is consistent with the standard model prediction