bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended reduced-form framework for non-life insurance
Authors: Biagini Francesca , Zhang Yinglin
Published: June 2022

In this paper we propose a general framework for modeling an insurance liability cash flow in continuous time, by generalizing the reduced-form framework for credit risk and life insurance. In particular, we assume a nontrivial dependence structure between the reference filtration and the insurance internal filtration. We apply these results for pricing and hedging non-life insurance liabilities in hybrid financial and insurance markets, while taking into account the role of inflation under the benchmarked risk-minimization approach. This framework offers at the same time a general and flexible structure, and an explicit and treatable pricing-hedging formula.
Business portfolio reconfiguration and firm performance: The contingency role of organizational capabilities, slack and ownership
Authors: Chen Kuo-Liang , Chen Chung-Jen , Hsieh Jia-Shiuan , Lin Ya-Hui
Published: June 2022

The purpose of this study aims to explore the relationships between business portfolio reconfiguration and firm performance in developing countries as well as the moderating roles played by organizational slack, capabilities and ownership structure. By using the perspectives of dynamic capabilities, resources-based view and social network, this study proposes that there is aU-shaped relationship between business portfolio reconfiguration and firm performance. Furthermore, while R&D capability, marketing capability and foreign ownership are expected to positively moderate thisU-shaped relationship, organizational slack, state and domestic ownership may potentially make thisU-shaped relationship less pronounced. We draw our observations from Shanghai and Shenzhen Stock Exchanges in China from 2008 to 2017, and obtain 26,151 firm-year observations, which are consisted of 3,508 publicly traded companies. The results generally support our hypotheses, and some theoretical and practical implications are extracted from this study.
Why Join the Fed?
Authors: Calomiris Charles W. , Jaremski Matthew
Published: June 2022

We study the decisions of state-chartered banks to join the Fed in its first decade. Ours is the first study to combine state regulatory environment characteristics and individual bank characteristics to explain Fed membership choice. Regulatory environments that reduced the benefit of discount window access or increased the regulatory cost of joining the Fed led to fewer banks joining. Individual bank characteristics that affected the magnitude of benefits from accessing the discount window (either passing on liquidity risk reduction to respondents or reducing the member bank’s own seasonal liquidity risk) were even more important in determining which banks joined.

I believe that, through the Federal Reserve Banks, … the better shall we be equipped to cope with the problems ahead of us, of helping ourselves and of helping the world; I believe it to be the duty of every bank in the country to contribute its share in equipping our nation for this task; … I firmly believe that the future will belong to those banks—national or state—that are members of the Federal Reserve System.

—Paul Warburg, Speech at the New York State Bankers’ Association Convention, 9 June 1916
Current status of Clonorchis sinensis and clonorchiasis in Korea: epidemiological perspectives integrating the data from human and intermediate hosts
Authors: Yoo Won Gi , Sohn Woon-Mok , Na Byoung-Kuk
Published: June 2022

Clonorchis sinensis is a carcinogenic liver fluke that causes clonorchiasis in humans. Clonorchiasis is prevalent in East Asian countries, and approximately 15–20 million individuals are estimated to be infected with this fluke globally. This review highlights the current status of C. sinensis and clonorchiasis in Korea from the epidemiological perspective involving the analysis of humans and intermediate hosts. Despite the recent decline in C. sinensis infection rate in Korea, C. sinensis infections remain endemic in 5 major river basins (Han-gang, Geum-gang, Seomjin-gang, Yeongsan-gang and Nakdong-gang; gang means river) with a high incidence of cholangiocarcinoma. A noticeable pattern involves increasing mild infections among patients diagnosed positive for C. sinensis eggs. The infection rate of C. sinensis metacercariae in the second intermediate host, freshwater fish, is also maintained at a substantial level. Thus, the One Health approach integrating different sectors and disciplines is recommended to accelerate and sustain control of C. sinensis, thereby leading to successful eradication. Health promotion via information dissemination and health education should be extended to prevent the consumption of raw freshwater fish by residents living in high-risk areas.
Viewing the World through Cosmovision at Late Preclassic Noh K'uh in Chiapas, Mexico
Authors: Juarez Santiago
Published: June 2022

This article examines how landscape modification was key to the development of an urbanizing society within a valley in Chiapas, Mexico. The Late Preclassic (400bc–ad250) site of Noh K'uh demonstrates how both the altered and unaltered environment signified the importance of cosmological concepts within this society. In an area rich with mountains and caves, the natural landscape offered residents opportunities to create symbolically meaningful living spaces. Evidence from local settlements reveals how the cosmological universe played a guiding role during the site's peak growth period, suggesting that other common contributors (such as economic and militaristic needs) of expansion may have been secondary.
Enlarged Field of View in Spatially Modulated Selective Volume Illumination Microscopy
Authors: Calisesi Gianmaria , Ancora Daniele , Tacconi Carlotta , Fantin Alessandro , Perin Paola , Pizzala Roberto , Valentini Gianluca , Farina Andrea , Bassi Andrea
Published: June 2022

Three-dimensional fluorescence microscopy is a key technology for inspecting biological samples, ranging from single cells to entire organisms. We recently proposed a novel approach called spatially modulated Selective Volume Illumination Microscopy (smSVIM) to suppress illumination artifacts and to reduce the required number of measurements using an LED source. Here, we discuss a new strategy based on smSVIM for imaging large transparent specimens or voluminous chemically cleared tissues. The strategy permits steady mounting of the sample, achieving uniform resolution over a large field of view thanks to the synchronized motion of the illumination lens and the camera rolling shutter. Aided by a tailored deconvolution method for image reconstruction, we demonstrate significant improvement of the resolution at different magnification using samples of varying sizes and spatial features.
Veränderung des religiös- spirituellen Befindens während des qualifizierten Entzugs von Alkohol
Authors: Freund Henning , Neddens Anne-Katharina , Bacchus Mareike , Uphaus Mirja , Steffens Markus
Published: June 2022

Zusammenfassung: Hintergrund: Die Rolle von Religion und Spiritualität (R/S) bei Suchterkrankungen ist vergleichsweise gut untersucht, insbesondere im Rahmen des Programms der Zwölf Schritte der Anonymen Alkoholiker. Im Gegensatz dazu wissen wir fast nichts über die Rolle von Religion und Spiritualität in der frühen Behandlungsphase der Entgiftung. Zielsetzung: In dieser Pilotstudie wird die Hypothese einer Steigerung des Religiös-Spirituellen Befindens (RSB) während der Qualifizierten Entzugsbehandlung überprüft. Methodik: Dazu wurden 52 Patient_innen (36 m, 16 w) mit Abhängigkeitssyndrom von Alkohol (F 10.2.) zu Beginn und zum Abschluss ihres stationären Qualifizierten Entzugs mit einem Fragebogen zum RSB untersucht. Ergebnisse: Hypothesenkonform (einseitige Fragestellung, 5 % Niveau) konnte eine Zunahme des Gesamtscore RSB während der Behandlungszeit festgestellt werden (p = .007, d = 0.40). Dabei zeigte sich auf der Subskala Hoffnung (immanent) die größte Veränderung (p < .001, d = 0.51), während die fünf anderen Subskalen keine statistisch signifikanten Steigerungen aufwiesen. Schlussfolgerungen: Diskutiert werden mögliche Selektionseffekte bei der Stichprobe und die praktische Bedeutung von Hoffnung als Ressource für die Behandlung von Suchterkrankungen.
Sources of the Levantine Intermediate Water in Winter 2019
Authors: Taillandier V. , D’Ortenzio F. , Prieur L. , Conan P. , Coppola L. , Cornec M. , Dumas F. , Durrieu de Madron X. , Fach B. , Fourrier M. , Gentil M. , Hayes D. , Husrevoglu S. , Legoff H. , Le Ster L. , Örek H. , Ozer T. , Poulain P. M. , Pujo‐Pay M. , Ribera d’Alcalà M. , Salihoglu B. , Testor P. , Velaoras D. , Wagener T. , Wimart‐Rousseau C.
Published: June 2022

Climatic changes and interannual variability in the Mediterranean overturning circulation are crucially linked to dense water formation in the Levantine Sea, namely the Levantine Intermediate Water whose formation zone, comprising multiple and intermittent sources, extends over fluctuating pathways. To probe into the variability of this water formation and spreading, a unique dataset was collected during the winter of 2019 in the western Levantine Sea, via oceanographic cruises, profiling floats and a glider, at a spatio‐temporal distribution suited to resolve mesoscale circulation features and intermittent convection events. This study highlights the competition between two source regions, the Cretan Sea and the Rhodes Cyclonic Gyre, to supply the Mediterranean overturning circulation in Levantine Intermediate Water. The Cretan source was estimated as the most abundant, supported by increasingly saltier water masses coming from the Levantine Sea under the pumping effect of a water deficit caused by strong western outflow toward the Ionian Sea.
Fluid‐Driven Transport of Round Sediment Particles: From Discrete Simulations to Continuum Modeling
Authors: Zhang Qiong , Deal Eric , Perron J. Taylor , Venditti Jeremy G. , Benavides Santiago J. , Rushlow Matthew , Kamrin Ken
Published: June 2022

Bedload sediment transport is ubiquitous in shaping natural and engineered landscapes, but the variability in the relation between sediment flux and driving factors is not well understood. At a given Shields number, the observed dimensionless transport rate can vary over a range in controlled systems and up to several orders of magnitude in natural streams. Here, we (a) experimentally validate a resolved fluid‐grain numerical scheme (Lattice Boltzmann Method‐Discrete Element Method or DEM‐LBM), and use it to (b) explore the parameter space controlling sediment transport in simple systems. Wide wall‐free simulations show the dimensionless transport rate is not influenced by the slope, fluid depth, mean particle size, particle surface friction, or grain‐grain damping for gentle slopes (0.01–0.03) at a medium to high fixed Shields number. (c) Examination of small‐scale fluid‐grain interactions shows fluid torque is non‐negligible for the entrainment and sediment transport near the threshold. And (d) the simulations guide the formulation of continuum models for the transport process. We present an upscaled two‐phase continuum model for grains in a turbulent fluid and validate it against bedload transport DEM‐LBM simulations. To model the creeping granular flow under the bed surface, we use an extension of the Nonlocal Granular Fluidity model, which was previously shown to account for flow cooperativity from grain‐size‐effects in dry media. The model accurately predicts the exponentially decaying velocity profile deeper into the bed.
Simultaneous defect regulation by p–n type co-substitution in a Na3V2(PO4)3/C cathode for high performance sodium ion batteries
Authors: Liu Changcheng , Jiang Xiaomei , Huang Que , Chen Yanjun , Guo Li
Published: June 2022

The Na3V2(PO4)3 (NVP) cathode is deemed to be a promising candidate for sodium ion batteries due to its strong structural stability and high theoretical capacity.
The highly improved hydrogen evolution performance of a 0D/0D MoP-modified P-doped Mn0.5Cd0.5S photocatalyst
Authors: Yan Jiaowei , Wang Ying , Shi Lei
Published: June 2022

MoP-modified P-doped Mn0.5Cd0.5S composites were prepared and they showed excellent hydrogen production performance in pure water and sacrificial agent environments.
Access to densely functionalized spirocyclopentenonyl oxindole frameworks via aza- and carbo-Piancatelli rearrangement
Authors: Pramanik Sourav , Jagadeesh Chenna , Chatterjee Ayan , Debnath Subhas Chandra , Saha Jaideep
Published: June 2022

The Piancatelli rearrangement on an oxindole-based template enables access to highly functionalized spirooxindole moieties.
Beinvenenthrombose und Lungenembolie nach Varizensklerosierung
Authors: Elsner Peter , Meyer Jochen
Published: June 2022

Bei einer Patientin erfolgte unter der klinischen Diagnose „Venektasien Oberschenkel- und Unterschenkelbereich“ eine Schaumsklerosierungsbehandlung mittels Äthoxysklerolschaum. 5 Tage später stellte sich die Patientin mit starken Schmerzen im Wadenbereich und starker Behinderung beim Auftreten wieder vor, wobei nach klinischer Befunderhebung mit diskretem Rötungsnachweis der Verdacht auf eine Thrombophlebitis geäußert wurde. Die Behandlung erfolgte mit Ibuprofen. Ein Termin zu einer duplexsonografischen Untersuchung 11 Tage später wurde vereinbart, von der Patientin allerdings erst nach 16 Tagen wahrgenommen, wobei eine Phlebografie erfolgte, die eine tiefe Venenthrombose zeigte. Eine folgende stationäre Behandlung ergab zusätzlich eine Lungenarterienembolie.

Die Patientin bemängelte ihre Behandlung in der Hautarztpraxis. Durch eine fehlerhafte Verödungsbehandlung bzw. Nachkontrolle sei eine tiefe Thrombose mit nachfolgender Lungenembolie nicht erkannt worden und durch Verkennung offenkundiger Symptome eine Falschbehandlung erfolgt.

Von einem hinzugezogenen dermatologischen Gutachter und der Schlichtungsstelle wurde ein Behandlungsfehler bestätigt. Die Verödungstherapie stellte zwar eine anerkannte Behandlungsmethode der Varikosis nach Facharztstandard dar. Eine tiefe Venenthrombose nach Sklerosierungstherapie ist zwar sehr selten, jedoch wären nach Wiedervorstellung der Patientin wegen erheblicher Beschwerden weiterführende diagnostische Maßnahmen, insbesondere eine duplexsonografische Abklärung, ohne wesentliche Zeitverzögerung indiziert gewesen. Es handelte sich um einen Befunderhebungsmangel, der im konkreten Fall zu einer Beweislastumkehr hinsichtlich der Kausalität des Behandlungsfehlers für den eingetretenen Schaden führte.

Nach endovenösen Eingriffen bei Varikosis sind tiefe Venenthrombosen mit dem Risiko einer Lungenembolie seltene, aber typische Komplikationen. Bei nach einer Schaumsklerosierung auftretenden Extremitätenschmerzen sollte eine tiefe Venenthrombose differenzialdiagnostisch erwogen und unverzüglich durch eine Duplexsonografie und Bestimmung der D-Dimere bestätigt oder ausgeschlossen und ggf. leitliniengerecht therapiert werden. Die Verzögerung eines indizierten Thromboseausschlusses kann als schuldhafter Befunderhebungsfehler mit der Folge der Beweislastumkehr gewertet werden.
Interventionelle Behandlungsoptionen bei vaskulären Malformationen
Authors: Müller-Wille René , Wildgruber Moritz , Wohlgemuth Walter A.
Published: June 2022

Klassifikation von vaskulären Malformationen Während Hämangiome zu den vaskulären Tumoren zählen, sind vaskuläre Malformationen angeboren und bilden sich von selbst nicht zurück. Sie werden nach der ISSVA-Klassifikation unterschieden.

Indikation zur Therapie Ziele der Therapie von Gefäßmalformationen sind die Linderung der Symptome, der Organerhalt und die Verhinderung von Krankheitsprogress und Komplikationen.

Nichtinvasive Therapieoptionen Die Kompressionstherapie sowie physiotherapeutische Maßnahmen zählen zu den wichtigsten konservativen Therapieoptionen.

Invasive Therapieoptionen Die chirurgische Resektion, die oberflächliche Lasertherapie und die interventionelle Therapie stellen die invasiven Therapieoptionen dar. Für die Behandlung symptomatischer Gefäßmalformationen stehen mittlerweile zahlreiche minimalinvasive interventionelle Verfahren zur Verfügung. Slow-Flow-Malformationen können relativ komplikationsarm mittels perkutaner Sklerotherapie behandelt werden, die zu einem zeitversetzten entzündlichen Verschluss der Läsion führt. Dysplastische Venen wie die Marginalvene können mittels endoluminaler Verfahren erfolgreich verödet werden. Die zumeist Katheter-gesteuerten Embolisationsverfahren mittels Flüssigembolisaten, Plugs und Coils erlauben den Verschluss von Fast-Flow-Gefäßmalformationen.
Seltenes Schnapp-Phänomen in der proximalen ischiocruralen
Muskulatur einer 62-jährigen Pflegekraft
Authors: Schröder Achim , Greitemann Bernhard , Scharbrodt Astrid , Brinker Tatjana
Published: June 2022

Schnappende oder springende Phänomene im Hüftbereich werden durch
verschiedene angeborene oder erworbene biomechanische Störungen
hervorgerufen. Der Begriff „Schnappende Hüfte“ ist etabliert
und bezieht sich allerdings auf Störungen an der lateralen oder ventralen
Hüfte. Eine dorsal in der rückseitigen Oberschenkelmuskulatur
lokalisierte Störung ist höchst selten. Für die betroffene
Patientin ergaben sich auch sozialmedizinische Konsequenzen.
Männer- und Frauenhaut – Genderaspekte
Authors: Bayerl Christiane
Published: June 2022

Männer- und Frauenhaut sind unterschiedlich. Männerhaut ist dicker, hat mehr Talgdrüsen und Oberflächenlipide, eine höhere, nicht so divergente Keimzahl wie Frauen, niedrigere transepidermale Wasserverlust (TEWL)-Werte und einen niedrigeren pH-Wert. Die Wundheilung und das Niveau von Antioxidantien ist bei Frauenhaut besser. Männerhaut hat mehr Kollagen, altert an anderer Lokalisation, bei Männern finden sich mehr Falten an der Stirn, bei Frauen mehr Falten perioral. Studien sollten die Auswertung der Daten nach Geschlechtern mit beachten.
Air flow over a flapping bird’s wing at low Reynolds numbers: discussions in a teaching demonstration
Authors: Williams Hollis
Published: June 2022

Bird wings are frequently modelled in the aerodynamics literature under the assumption that they are static aerofoils. Air flows over real bird wings can violate this assumption, both because of the topology of the wing and the fact that real wings typically undergo flapping and twisting motions during flight. There are many computational and numerical studies of air flows on flapping bird’s wings at low Reynolds numbers, but relatively few experimental studies due to the difficulty of modelling a realistic flapping motion. In this article, the flow on a real flapping bird wing is visualised in a teaching demonstration using high-speed photography. It is found that the main features of the flow can be observed and that the demonstration is a teaching aid for assisting student understanding of principles of aerodynamics. The possibility of incorporating the demonstration into a standard teaching course is discussed, with relevant teaching objectives highlighted. In conclusion, it is recommended that the demonstration could be useful as part of a course on aerodynamics, with further follow-up demonstrations and studies suggested.
Membrane-boundd-mannose isomerase of acetic acid bacteria: finding, characterization, and application
Authors: Adachi Osao , Kataoka Naoya , Matsushita Kazunobu , Akakabe Yoshihiko , Harada Toshihiro , Yakushi Toshiharu
Published: June 2022

d-Mannose isomerase (EC 5.3.1.7) catalyzing reversible conversion between d-mannose and d-fructose was found in acetic acid bacteria. Cell fractionation confirmed the enzyme to be a typical membrane-bound enzyme, while all sugar isomerases so far reported are cytoplasmic. The optimal enzyme activity was found at pH 5.5, which was clear contrast to the cytoplasmic enzymes having alkaline optimal pH. The enzyme was heat stable, and the optimal reaction temperature was observed at around 40-60 °C. Purified enzyme after solubilization from membrane fraction showed the total molecular mass of 196 kDa composing of identical 4 subunits of 48 kDa. Washed cells or immobilized cells were well functional at nearly 80% of conversion ratio from d-mannose to d-fructose and reversely 20%-25% of d-fructose to d-mannose. Catalytic properties of the enzyme were discussed with respect to the biotechnological applications to high fructose syrup production from konjac taro.
A simple and general debiased machine learning theorem with finite-sample guarantees
Authors: Chernozhukov V , Newey W K , Singh R
Published: June 2022

Debiased machine learning is a meta-algorithm based on bias correction and sample splitting to calculate confidence intervals for functionals, i.e., scalar summaries, of machine learning algorithms. For example, an analyst may seek the confidence interval for a treatment effect estimated with a neural network. We present a non-asymptotic debiased machine learning theorem that encompasses any global or local functional of any machine learning algorithm that satisfies a few simple, interpretable conditions. Formally, we prove consistency, Gaussian approximation and semiparametric efficiency by finite-sample arguments. The rate of convergence is $n^{-1/2}$ for global functionals, and it degrades gracefully for local functionals. Our results culminate in a simple set of conditions that an analyst can use to translate modern learning theory rates into traditional statistical inference. The conditions reveal a general double robustness property for ill-posed inverse problems.
Serum Levels of Infliximab Biosimilar in a Child Delivered From a Mother Treated for Ulcerative Colitis
Authors: Kawamoto Ami , Fujii Toshimitsu , Mitani Ryuji , Suzuki Yasuhiro , Yauchi Tsunehito , Okamoto Ryuichi
Published: June 2022

Lay Summary

The infliximab biosimilar CT-P13 is used for the treatment of ulcerative colitis. We report for the first time the serum drug levels and long-term health status of the child of a patient treated with CT-P13 throughout her pregnancy.
Combined mitral valve replacement and coronary artery bypass grafting through a left thoracotomy after retrosternal oesophageal reconstruction
Authors: Numaguchi Ryosuke , Shiiku Chikara
Published: June 2022

A 74-year-old man with a history of retrosternal oesophageal reconstruction was referred for surgical treatment of mitral valve regurgitation and coronary artery disease. He underwent mitral valve replacement combined with coronary artery bypass grafting through a left thoracotomy. Combined mitral valve replacement and coronary artery bypass grafting through a left thoracotomy were feasible in this patient with a retrosternal neo-oesophageal conduit.
Strategy for lung parenchyma-sparing bronchial resection: a case series report
Authors: Ohsumi Akihiro , Kayawake Hidenao , Yamada Yoshito , Tanaka Satona , Yutaka Yojiro , Nakajima Daisuke , Hamaji Masatsugu , Menju Toshi , Date Hiroshi
Published: June 2022

Lung parenchyma-sparing bronchial resection is uncommon, and the operative procedure depends on the cause and location of the stenosis. We present 6 cases and discuss the different surgical strategies for sleeve resection of the central airway without lung resection. Bronchoplasty for the main bronchus and truncus intermedius was performed with a posterolateral approach. We resected the right main bronchus including the right lateral wall of the lower trachea and half of the carina obliquely and performed an anastomosis. The tumour in the left lobar bronchus was exposed and removed by transient division of the accompanying pulmonary artery. Although post-transplant stenosis and malacia can pose a challenge, bronchoplasty can be used as a definitive treatment in experienced centres.
A Novel Locus on 6p21.2 for Cancer Treatment–Induced Cardiac Dysfunction Among Childhood Cancer Survivors
Authors: Sapkota Yadav , Ehrhardt Matthew J , Qin Na , Wang Zhaoming , Liu Qi , Qiu Weiyu , Shelton Kyla , Shao Ying , Plyler Emily , Mulder Heather L , Easton John , Michael J Robert , Burridge Paul W , Wang Xuexia , Wilson Carmen L , Jefferies John L , Chow Eric J , Oeffinger Kevin C , Morton Lindsay M , Li Chunliang , Yang Jun J , Zhang Jinghui , Bhatia Smita , Mulrooney Daniel A , Hudson Melissa M , Robison Leslie L , Armstrong Gregory T , Yasui Yutaka
Published: June 2022

Background

Adult survivors of childhood cancer are at increased risk of cardiac late effects.

Methods

Using whole-genome sequencing data from 1870 survivors of European ancestry in the St. Jude Lifetime Cohort (SJLIFE) study, genetic variants were examined for association with ejection fraction (EF) and clinically assessed cancer therapy–induced cardiac dysfunction (CCD). Statistically significant findings were validated in 301 SJLIFE survivors of African ancestry and 4020 survivors of European ancestry from the Childhood Cancer Survivor Study. All statistical tests were 2-sided.

Results

A variant near KCNK17 showed genome-wide significant association with EF (rs2815063-A: EF reduction = 1.6%; P = 2.1 × 10-8) in SJLIFE survivors of European ancestry, which replicated in SJLIFE survivors of African ancestry (EF reduction = 1.5%; P = .004). The rs2815063-A also showed a 1.80-fold (P = .008) risk of severe or disabling or life-threatening CCD and replicated in 4020 Childhood Cancer Survivor Study survivors of European ancestry (odds ratio = 1.40; P = .04). Notably, rs2815063-A was specifically associated among survivors exposed to doxorubicin only, with a stronger effect on EF (3.3% EF reduction) and CCD (2.97-fold). Whole blood DNA methylation data in 1651 SJLIFE survivors of European ancestry showed statistically significant correlation of rs2815063-A with dysregulation of KCNK17 enhancers (false discovery rate <5%), which replicated in 263 survivors of African ancestry. Consistently, the rs2815063-A was associated with KCNK17 downregulation based on RNA sequencing of 75 survivors.

Conclusions

Leveraging the 2 largest cohorts of childhood cancer survivors in North America and survivor-specific polygenomic functional data, we identified a novel risk locus for CCD, which showed specificity with doxorubicin-induced cardiac dysfunction and highlighted dysregulation of KCNK17 as the likely molecular mechanism underlying this genetic association.
#42 A Retrospective Study of Valganciclovir Discontinuation Due to Toxicity or Intolerance in Pediatric Solid Organ Transplant Patients
Authors: Demirhan Salih
Published: June 2022

Background

Cytomegalovirus (CMV) prevention strategies in pediatric solid organ transplantation (SOT) recipients include universal prophylaxis or pre-emptive therapy with valganciclovir (VGCV) based on CMV risk stratification. However, VGCV is associated with myelosuppresion and nephrotoxicity, which may result in premature termination or dose modifications of VGCV and/or discontinuation of Pneumocystis jirovecii pneumonia (PJP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX), which is also myelosupressive. There are no currently approved alternatives for CMV prevention in pediatric SOT patients. Thus, the specific aims of this study were to determine the frequency with which SOT recipients receiving VGCV develop neutropenia or lymphopenia, how often VGCV or TMP-SMX are discontinued or have a dose reduction, and whether changes in CMV prophylaxis are associated with increased rates of CMV DNAemia or disease.

Method

A retrospective, observational study of pediatric SOT recipients who were < 20 years old and who initiated VGCV prophylaxis, with the intent to receive at least 3 months of therapy, was conducted at 8 U.S. centers between January 2016 and December 2019. Each site abstracted demographic and clinical data for 1 year post-transplantation into a central REDCap electronic database hosted at St Jude. Patients with complete information as of December 2021 (n= 557) were included in this preliminary analysis.

Results

The cohort included 201 renal (36%), 101 cardiac (18%), 202 liver (36%), 34 lung (6%), 10 multivisceral (2%), 2 intestinal and 6 other SOT recipients. Median age at transplantation was 9.5 [IQR: 2.7- 14] years; 52% were male. VGCV was prematurely discontinued in 31 and the dose was adjusted in 168 resulting in changes in 199 (36%) recipients. TMP-SMX was discontinued prematurely in 61 and changed to an alternative therapy in 77 patients resulting in changes in 131 (24%) recipients. Seven patients discontinued both medications. No breakthrough cases of Pneumocystis pneumonia were documented. There were 119 (21%) patients with at least one episode of CMV DNAemia in the first year post-transplant, 54 (45%) of these occurred in patients who had changes to their VGCV prophylaxis.

Conclusion

Preliminary analysis of this large pediatric cohort suggests that CMV prophylaxis with VGCV is difficult to maintain and requires frequent dose adjustments and/or discontinuation of either VGCV and/or TMP-SMX for PJP prophylaxis. Despite alterations in PJP prophylaxis, no breakthrough infections were documented. These findings highlight the need to study the safety and efficacy of alternative prophylactic options for CMV in pediatric SOT recipients.
#12 Comparing Treatment of Pediatric Bronchiolitis and Upper Respiratory Infections in Primary, Tertiary, and Urgent Care Settings
Authors: Dellplain Laura
Published: June 2022

Background

Pediatric bronchiolitis and upper respiratory infections (URI) are almost always of viral origin and thus managed without antibiotics. Inappropriate antibiotic use for such diagnoses can contribute to antimicrobial resistance. We assessed the appropriateness of pediatric bronchiolitis and URI treatment in primary, tertiary, and urgent care settings within a large private health system in Upstate New York and compared treatment appropriateness between the three settings.

Method

We conducted a retrospective, observational chart review of patient visits in pediatric primary, pediatric tertiary, and urgent care settings where there was a presumptive diagnosis of bronchiolitis or URI between January 1 and December 31, 2019 using ICD-10 diagnostic codes. We assessed patient treatment for each visit as “appropriate,” “possibly appropriate,” or “inappropriate” based on extracted chart data. We performed simple proportion calculations for each treatment category in each care setting, and then compared proportions for each treatment category between settings using chi-square and logistic regression models.

Results

Of the 450 patient visits reviewed in each care setting, 354 primary care, 375 tertiary care, and 442 urgent care visits met the inclusion criteria. Table 1 shows the proportion of appropriate, possibly appropriate, and inappropriate visits in the primary, tertiary, and urgent care settings. The tertiary care and urgent care settings had a statistically significant proportion of possibly appropriate or inappropriate encounters at 2.4% and 4.8% respectively. In comparing odds ratios for possibly appropriate or inappropriate treatment of pediatric bronchiolitis and URIs between care settings, urgent care setting treatments were 5.77 times more likely to be inappropriate or possibly appropriate than in pediatric primary care settings (95% CI [1.71, 19.5]). Differences in treatment between primary and tertiary care settings and tertiary and urgent care settings were not statistically significant.

Conclusion

In 2019, nearly all reviewed encounters in the pediatric primary, pediatric tertiary, and urgent care settings within a large private health system in Upstate New York adhered to clinical guidelines for bronchiolitis and URI treatment. However, the urgent care setting had a significantly greater odds of possibly appropriate or inappropriate treatment of these pediatric infections, highlighting an opportunity for further education and intervention to improve guideline adherence for bronchiolitis and URI management in that setting.
#21 High Caregiver Adverse Childhood Experiences are Associated with Influenza and COVID-19 Vaccination Acceptance in One Pediatric Primary Care Site
Authors: Day Melissa E
Published: June 2022

Background

Vaccine hesitancy is complex, ranging from safety concerns to decisions built atop disinformation and medical mistrust. Though distrust towards healthcare providers has been described in those with adverse childhood experiences (ACEs), studies have not assessed for links between caregiver ACEs and pediatric vaccine refusal. We sought to determine the association between caregiver ACEs and caregiver decisions to immunize their child with influenza and COVID-19 vaccines.

Method

This was a cross-sectional study of caregivers of patients >6 months at one pediatric primary care center. Caregivers completed a 19-question survey to determine ACE score, influenza vaccine acceptance and beliefs (adapted from a CDC-validated survey), and intention to accept the COVID-19 vaccine for their children. Demographic characteristics, social risk factors (e.g. housing and food insecurity), social work notes or medical legal partnership referrals within 3 days of a clinic visit, and vaccination data of the children present with each caregiver were extracted from the electronic medical record. Statistical analyses included chi-square tests for categorical variables and t-tests for age. The chi-square test was used to determine the association between caregiver ACEs (high versus low) and demographic, social risk factors and vaccination acceptance, and the two-sample t-test was used to test for differences in child age.

Results

A total of 234 caregivers participated, representing 276 patients (mean age of 5.9 years, 52% male). Of participating caregivers, 24% (n = 56) had high ACEs (score ≥ 4) and 38% (n = 88) accepted influenza vaccination for their child in 2021. Of those with high ACEs, 51% accepted influenza vaccination for their child compared to 34% with low ACEs (p = 0.03). Those with high ACEs also had more positive attitudes toward influenza vaccine safety and efficacy (p=0.01). Intention to vaccinate children with COVID-19 vaccine also varied by caregiver ACE score (high ACEs: 40%; low ACEs: 24%; p=0.03). Insurance type, a positive social risk screen, and social work consult were not associated with ACEs (Table 1).

Conclusion

Influenza vaccination rates and intention to vaccinate children with the COVID-19 vaccine differed between caregivers with high and low ACEs – those with more ACEs were more likely to vaccinate. Further studies assessing the role of caregiver ACEs on vaccine decision-making is warranted.
#38 The Impact of the COVID-19 Pandemic on Acute Appendicitis Presentation in Two Urban Multiethnic Community Hospitals
Authors: Mallikarjuna Priya
Published: June 2022

Background

Acute appendicitis (AA) is the most common abdominal surgical emergency in pediatrics. There was a precipitous drop in pediatric visits to hospitals, including the emergency department, since the United States declared COVID-19 a national emergency. Managing AA during the pandemic remains a challenge as fear of COVID exposure can lead to delays in presentation and surgery, as well as a shift to conservative management. Alvarado score (AS) is a ten-point clinical scoring system to identify AA and the American Association for the Surgery of Trauma (AAST) grading system (I-V) is a validated tool for AA diagnosis and severity. There are no studies on prevalence and severity of AA during the COVID-19 pandemic in an urban multiethnic community.

Method

This is a retrospective chart review of patients admitted to Flushing Hospital Medical Center and Jamaica Hospital Medical Center with the diagnosis of AA from March 2018 to March 2021. Charts were reviewed for demographics, clinical, imaging and surgical data to determine AS and AAST. AS grouped from 1-6 (less likely to require surgery) and 7-10 (more likely to require surgery). AAST scoring was based on most severe criteria if grading discrepancies were found between pathology, surgical and computed tomography findings. Leukocytosis was defined as white blood cell count >10. G1 identified AA cases March 2018 - February 2020 and G2 March 2020 – March 2021. Data was analyzed using SPSS software, p<0.05 was considered significant.

Results

Of 239 patients with AA over 3 years, G1 totaled 184 (77%) in 2 years pre-pandemic and G2 had 55 (23%) during first year pandemic. Mean age, gender and ethnicity were similar for G1 and G2. AS and AAST were compared for G1 and G2, Table 1. G2 had significantly greater overall AS of >7 (p=0.038) and higher AAST (p=0.016). Only three patients tested positive for SARS-CoV-2 and 9 (16%) of G2 were transferred to a tertiary care center.

Conclusion

Although there was a decline in number of AA evaluated in our emergency department, the severity of AA was heightened during the pandemic. Healthcare providers need to have a high index of suspicion of increased severity with AA complications.
#48 Stenotropomonas maltophilia infection in the Neonatal Intensive Care Unit: A retrospective study of risk factors and outcome in a tertiary hospital in New York.
Authors: Khan Sana Irfan
Published: June 2022

Background

Stenotrophomonas maltophilia (S maltophilia) remains an important nosocomial gram-negative bacillus on the rise with limited studies in the neonatal population. The aim of the present study was to review the risk factors and outcomes of S maltophilia infections in the level 3 neonatal intensive care unit (NICU) of a tertiary hospital in Brooklyn, New York City.

Method

A retrospective review and analysis of electronic medical records of patients admitted to NICU with culture positive S maltophilia and matched controls in a period of 12 years from 2008-2020 was carried out. The JMP 10.0 (SAS Institute Inc., Cary, NC, USA) software package was used for data analyses. T-test was used to determine if there was a significant difference between the data of interest among cases and controls. Values of p <0.05 were considered statistically significant.

Results

Twenty-one cases of S maltophilia were compared with 42 controls in the study (case control ratio of 1:2). Of the 21 patients with S maltophilia infections, 13 (70%) were females and 8 (30%) were males. The median birth weight of neonates with S maltophilia infection was 705g versus 770.5g in the control group. The median length of NICU stay in culture positive cases was 134 days while the median duration in control was 92 days (p<0.01). The median duration of total parenteral nutrition (TPN) was 113.5 days in cases while it was 19.5 days in control (p<0.001). The median duration of mechanical ventilation in cases was 54 days versus 20.5 days in control (<0.01). The median duration of antibiotic use was 67.5 days in cases while it was 23 days in the control group (p<0.01). Six patients in the cases group underwent abdominal surgery and the overall mortality rate in the case group was 28.5%.

Conclusion

This study demonstrated that invasive interventions such as mechanical ventilation and TPN are associated with S maltophilia infection. In addition, long hospital stays and extended antibiotic use are risk factors. Efforts to reduce exposure to the identified risk factors are essential to prevent infections in this population given the high mortality. In particular, antimicrobial stewardship programs have the potential to reduce number of days on antibiotics and other risk factors as well as provide guidance on diagnosis and treatment in infected neonates.
#49 Nasal microbiota differences in young infants are associated with early childhood irritability
Authors: Mithal Leena
Published: June 2022

Background

The etiology and pathophysiology of childhood mental health are poorly understood. Early childhood irritability is a transdiagnostic marker that portends significant risk for subsequent mental health problems. Robust evidence demonstrates irritability can be quantified early in infancy. The early life microbiome is implicated in defining health trajectories including neurodevelopment. In contrast to the gut microbiome, however, a relationship between the infant nasal microbiome and early childhood irritability remains undefined. We sought to investigate associations between the nasal microbiota of infants <60 days of age and early childhood irritability.

Method

This case-control study included infants with archived respiratory nasal samples collected for routine clinical care at ≤60 days of age from an emergency department visit (1/2016-5/2019). Parents completed an online survey when children were 14-42 months of age that included questions about medical history, development, and irritability (Multidimensional Assessment of Preschool Disruptive Behavior, MAP-DB). The upper quartile of the MAP-DB Temper Loss Score was classified as high dysregulation. Additional clinical data were collected from the electronic health record. DNA extracted from archived viral media specimens were subjected to 16S rRNA gene (V3-V4 region) next generation sequencing (NGS). Ecological diversity and differential taxon analysis were performed.

Results

Seventy-two children were initially included, with 16 categorized as high dysregulation. The median age at nasal sample collection was 30 days (IQR 14-44), and age at parent survey was 28 months (IQR 19-31). Fifty-weight percent of the cohort was white, 6% Black, 6% Asian, 20% other, and 25% identified as Lantine ethnicity. The infants were 49% female sex, 77% were born by vaginal delivery, and 43% had a virus identified at time of nasal sample. After removal of extraction/PCR contaminants, taxa present only or at higher levels in media, and samples with <80 sequences, the final microbiota comparison dataset was n=33 children, 7 with high dysregulation. Alpha-diversity (Shannon index) was lower in the high dysregulation group (p=0.0031 pre-background taxa removal, p=0.1288 post-correction, Figure 1A-B). Of the 18 taxa that were compared, Haemophilus, Streptococcus, Staphylococcus, and Gardnerella were significantly less abundant in the high dysregulation group (false discovery corrected significance q<0.005, Figure 1C). Parasutterella was more abundant in a subset of the high dysregulation group.

Conclusion

Differences in the nasal microbiota of infants, decreased diversity and abundance of certain respiratory bacteria, are associated with early childhood irritability, a marker of mental health risk. Further study may provide mechanistic insights and potentially guide new risk assessment or treatment options.
#62 Resolution of thrombocytopenia during treatment for symptomatic congenital cytomegalovirus disease
Authors: Walcott Shelby
Published: June 2022

Background

Congenital cytomegalovirus (cCMV) is the most common congenital viral infection in the United States (4.5 per 1000 live births) and is the leading non-genetic cause of sensorineural hearing loss and developmental disabilities in children worldwide. However, reliable estimates of time to resolution for manifestations of cCMV disease have not been fully elucidated. A better understanding of the resolution of laboratory abnormalities for cCMV is needed to guide decisions about frequency of platelet assessments following diagnosis and potentially optimize antiviral therapy.

Method

Data from 243 infants with symptomatic cCMV were retrospectively analyzed from four studies conducted by the NIH-funded Collaborative Antiviral Study Group over the years 1989-2011. Individuals were compared based on baseline platelet value, utilizing Division of AIDS Toxicity Scale categorization, and treatment received. Kinetics of the trend in platelets over time were compared between groups using Kaplan-Meier plots and binomial assessments of abnormal vs. normal. All analyses were conducted over the 6-week (45 day) time period.

Results

Predicted curves showed that the interaction between antiviral therapy and platelet value over time was found to be significant (p=0.0106) for individuals with normal baseline platelet counts (Grade 0, defined as ≥ 125,000). For individuals with Grades 1-4 thrombocytopenia at baseline, probability curves showed that both baseline grade (p=0.0006) and time (p<.0001) correlated with rate of resolution of thrombocytopenia, but antiviral treatment did not (p=0.1964). Kaplan-Meier plots of time to platelet count of ≥ 125,000 demonstrated that baseline platelet grade was significantly (p=0.0003) correlated with time to resolution of thrombocytopenia. Kaplan-Meier plots of time to platelet count of ≥ 100,000 demonstrated that baseline platelet grade was significantly (p=0.0056) correlated with time to Grade 1 thrombocytopenia.

Conclusion

For neonates with baseline thrombocytopenia from cCMV, antiviral therapy does not hasten time to resolution of thrombocytopenia. For neonates with normal baseline platelet values, antiviral therapy correlated with increasing platelet counts. Degree of baseline thrombocytopenia correlated with time to normalization of platelet count. Further understanding of the kinetics of resolution of laboratory abnormalities for symptomatic cCMV is needed to directly inform patient management decisions.
#64 Common Admission Diagnoses for Children Hospitalized with Respiratory Syncytial Virus and Antibiotic Administration Practices in Amman, Jordan
Authors: Rankin Danielle A
Published: June 2022

Background

Determining the etiologic pathogen for acute respiratory infections is challenging, especially in low- and middle-income countries, where diagnostic testing is limited. These barriers may contribute to antibiotic overuse for viral infections. We aimed to evaluate the antibiotic administration patterns among hospitalized children with a research positive test for respiratory syncytial virus (RSV).

Method

Children admitted to a government-run hospital in Amman, Jordan with acute respiratory symptoms and/or fever from January 8 to March 17, 2020, were eligible for enrollment. Trained personnel conducted interviews and chart abstractions using a standardized data collection form. Nasal and/or throat swabs were collected and tested for RSV by PCR. Differences between the three most common admission diagnoses for RSV-positive children [bronchiolitis, bronchopneumonia (BP), and pneumonia] were evaluated.

Results

A total of 531 children were enrolled and tested and 401 (76%) were RSV-positive, of which 96% received an antibiotic and 25%, 26%, and 32% had an admission diagnosis of bronchiolitis, BP, or pneumonia, respectively. Compared to bronchiolitis and BP, RSV-positive children with a pneumonia were younger and more likely to require supplemental oxygen, receive an antibiotic during hospitalization, be admitted to the ICU; but were less likely to present with wheezing and to report antibiotic use prior to hospitalization (Table 1). RSV-positive children with BP were more likely to present with fever and have a higher C-reactive protein compared to the other diagnoses, whereas bronchiolitis was less likely to be administered antibiotics overall, but more likely to be given a macrolide.

Conclusion

Our results suggest that clinical presentation alone is insufficient in correctly determining causative pathogens that warrant empiric antibiotics. Thus, evaluating the role of point-of-care diagnostic testing in resource-limited settings is important and may help limit antibiotic use.