bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocytes prime autoreactive T cells after myocardial infarction
Authors: DeBerge Matthew , Yu Shuangjin , Dehn Shirley , Ifergan Igal , Yeap Xin Yi , Filipp Mallory , Becker Amanda , Luo Xunrong , Miller Stephen , Thorp Edward B.
Published: December 2019

In humans, loss of central tolerance for the cardiac self-antigen α-myosin heavy chain (α-MHC) leads to circulation of cardiac autoreactive T cells and renders the heart susceptible to autoimmune attack after acute myocardial infarction (MI). MI triggers profound tissue damage, releasing danger signals and self-antigen by necrotic cardiomyocytes, which lead to recruitment of inflammatory monocytes. We hypothesized that excessive inflammation by monocytes contributes to the initiation of adaptive immune responses to cardiac self-antigen. Using an experimental model of MI in α-MHC-mCherry reporter mice, which specifically express mCherry in cardiomyocytes, we detected α-MHC antigen in myeloid cells in the heart-draining mediastinal lymph node (MLN) 7 days after MI. To test whether monocytes were required for cardiac self-antigen trafficking to the MLN, we blocked monocyte recruitment with a C-C motif chemokine receptor type 2 (CCR2) antagonist or immune modifying nanoparticles (IMP). Blockade of monocyte recruitment reduced α-MHC antigen detection in the MLN after MI. Intramyocardial injection of the model antigen ovalbumin into OT-II transgenic mice demonstrated the requirement for monocytes in antigen trafficking and T-cell activation in the MLN. Finally, in nonobese diabetic mice, which are prone to postinfarction autoimmunity, blockade of monocyte recruitment reduced α-MHC-specific responses leading to improved tissue repair and ventricular function 28 days after MI. Taken together, these data support a role for monocytes in the onset of pathological cardiac autoimmunity following MI and suggest that therapeutic targeting of monocytes may mitigate postinfarction autoimmunity in humans.

NEW & NOTEWORTHY Our study newly identifies a role for inflammatory monocytes in priming an autoimmune T-cell response after myocardial infarction. Select inhibition of monocyte recruitment to the infarct prevents trafficking of cardiac self-antigen and activation of cardiac myosin reactive T cells in the heart-draining lymph node. Therapeutic targeting of inflammatory monocytes may limit autoimmune responses to improve cardiac remodeling and preserve left ventricular function after myocardial infarction.
Prognostic Significance of Serum Uric Acid and Gamma-Glutamyltransferase in Patients with Advanced Gastric Cancer
Authors: Yang Shanshan , He Xinjia , Liu Ying , Ding Xiao , Jiang Haiping , Tan Ye , Lu Haijun
Published: December 2019

Purpose. In this study, we aim to evaluate the prognostic role of serum uric acid and gamma-glutamyltransferase in advanced gastric cancer patients. Methods. A total of 180 patients pathologically diagnosed with advanced gastric cancer were included in this retrospective study. We used time-dependent receiver operating characteristic (ROC) curves to identify the optimal cut-off value of serum uric acid (UA) and gamma-glutamyltransferase (GGT). Survival analysis was performed using the Kaplan–Meier method and log-rank test, and multivariate Cox regression analyses were applied. A nomogram was formulated, and the calibration and discrimination of the nomogram were determined by calibration curve and concordance index (C-index). We validated the results using bootstrap resampling and a separate study on 60 patients collected from 2015 to 2017 using the same criteria in other medical center. Results. Both higher serum uric acid (>228 μmol/L) and higher gamma-glutamyltransferase (>14 U/L) had worse OS and PFS. Univariate analysis indicated that serum uric acid (UA) (p<0.001 and p<0.001) and gamma-glutamyltransferase (GGT) (p<0.001 and p=0.044) were significantly related to overall survival (OS) and progression-free survival (PFS), respectively. Multivariate analysis revealed serum uric acid (UA) and gamma-glutamyltransferase (GGT) were independent prognostic factors for OS (p=0.012, p=0.001). The optimal agreement between actual observation and nomogram prediction was shown by calibration curves. The C-indexes of the nomogram for predicting OS and PFS were 0.748 (95% CI: 0.70-0.79) and 0.728 (95% CI: 0.6741-0.7819), respectively. The results were confirmed in the validation cohort. Conclusion. We observed that both serum UA and GGT were poor prognostic factors in patients with advanced gastric cancer. And we also formulated and validated a nomogram which can predict individual survival for advanced gastric cancer patients.
SIFO: Secure Computational Infrastructure Using FPGA Overlays
Authors: Fang Xin , Ioannidis Stratis , Leeser Miriam
Published: December 2019

Secure Function Evaluation (SFE) has received recent attention due to the massive collection and mining of personal data, but remains impractical due to its large computational cost. Garbled Circuits (GC) is a protocol for implementing SFE which can evaluate any function that can be expressed as a Boolean circuit and obtain the result while keeping each party’s input private. Recent advances have led to a surge of garbled circuit implementations in software for a variety of different tasks. However, these implementations are inefficient, and therefore GC is not widely used, especially for large problems. This research investigates, implements, and evaluates secure computation generation using a heterogeneous computing platform featuring FPGAs. We have designed and implemented SIFO: secure computational infrastructure using FPGA overlays. Unlike traditional FPGA design, a coarse-grained overlay architecture is adopted which supports mapping SFE problems that are too large to map to a single FPGA. Host tools provided include SFE problem generator, parser, and automatic host code generation. Our design allows repurposing an FPGA to evaluate different SFE tasks without the need for reprogramming and fully explores the parallelism for any GC problem. Our system demonstrates an order of magnitude speedup compared with an existing software platform.
Quantitative Evaluation of Karst Developmental Differences Based on Improved Analytic Hierarchy Process and Multidimensional Extension Matter Element Model
Authors: Wang Xinyi , Zou Yu , Wang Qi , Liu Xiaoman , Zhang Pingqing , Li Jianlin , Yao Mengjie
Published: December 2019

In this study, limestone solubility, rock thickness, burial depth, hydrodynamic cycle, and geological tectonic of mine No. 13 in the Pingdingshan coalfield (China) were selected to evaluate the degree of karst development. The weight of each index factor to the karst development was determined by using the improved analytic hierarchy process. The multidimensional extensional matter model was used to determine the degree of karst development of the four mining areas (named 1st to 4th) of the Pingdingshan mine No. 13. The results show that the degree of karst development differs zonally, with 1st and 2nd mining areas presenting the lowest degree of karst development (grade II-IV, for an average quantification value of 3.0) and 4th mining area having the highest degree (grade IV-V, for an average quantification value of 4.7). In the vertical direction, the development degree of the vertical layer L1-L4 karst in the Carboniferous Taiyuan Formation is grade IV-V, with an average quantitative value of 4.5, whereas the layers L5-L7 in the Taiyuan Formation had a III-V grade, with an average quantitative value of 3.75, and the Cambrian limestone grade was II-IV, for an average quantitative value of 2.75, i.e., the development degree of karst gradually decreases from shallow to deep.
Maintenance Therapy with FOLFIRI after FOLFIRINOX for Advanced Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis
Authors: Franck Caspar , Canbay Ali , Malfertheiner Peter , Venerito Marino
Published: December 2019

Objectives. Patients with pancreatic ductal adenocarcinoma (PDA) receiving FOLFIRINOX often develop oxaliplatin-induced polyneuropathy, which limits the continuation of this therapy. We evaluated the efficacy and safety of FOLFIRI maintenance treatment after FOLFIRINOX induction in a retrospective single-center study. Methods. Patients with advanced PDA treated with FOLFIRI as maintenance therapy after achieving disease control under FOLFIRINOX according to the local operating procedure between 2011 and 2016 were identified. Medical records of this group were evaluated retrospectively. Results. Overall, 22 patients with PDA were treated with FOLFIRI (mean age 59 years, 55% female, 45% male). Before receiving FOLFIRI, all patients were treated with FOLFIRINOX for a median of 4 months. The median progression-free survival (PFS) under FOLFIRI maintenance therapy was 8 months. Side effects grade 3-4 (CTCAE v4.0) were observed in 18% of patients receiving FOLFIRI. Considering together FOLFIRINOX induction and subsequent FOLFIRI maintenance therapy, the median PFS was 11 months. The median overall survival (OS) from the beginning of palliative treatment was estimated at 46 months. Conclusions. In the selected group of PDA patients achieving disease control with FOLFIRINOX, FOLFIRI maintenance therapy was feasible, safe, and effective, with some patients achieving long-term disease stabilization.
Preparation of Few-Layered WS2 and Its Thermal Catalysis for Dihydroxylammonium-5,5′-Bistetrazole-1,1′-Diolate
Authors: Shang Yiping , Yang Wu , Xu Yabei , Pan Siru , Wang Huayu , Cao Xiong
Published: December 2019

In this study, few-layered tungsten disulfide (WS2) was prepared using a liquid phase exfoliation (LPE) method, and its thermal catalytic effects on an important kind of energetic salts, dihydroxylammonium-5,5′-bistetrazole-1,1′-diolate (TKX-50), were investigated. Few-layered WS2 nanosheets were obtained successfully from LPE process. And the effects of the catalytic activity of the bulk and few-layered WS2 on the thermal decomposition behavior of TKX-50 were studied by using synchronous thermal analysis (STA). Moreover, the thermal analysis data was analyzed furtherly by using the thermokinetic software AKTS. The results showed the WS2 materials had an intrinsic thermal catalysis performance for TKX-50 thermal decomposition. With the few-layered WS2 added, the initial decomposition temperature and activation energy (Ea) of TKX-50 had been decreased more efficiently. A possible thermal catalysis decomposition mechanism was proposed based on WS2. Two dimensional-layered semiconductor WS2 materials under thermal excitation can promote the primary decomposition of TKX-50 by enhancing the H-transfer progress.
Effects of Selenium and Melatonin on Ocular Ischemic Syndrome
Authors: Telek Hande Hüsniye
Published: December 2019

Purpose. To determine the effects of selenium, melatonin, and selenium + melatonin administered for one month on anterior chamber (AC) malondialdehyde (MDA) and AC glutathione (GSH) levels in patients with ocular ischemic syndrome. Materials and Methods. Thirty-five patients were included in the study. Study groups were formed as follows: (1) control group, (2) ischemia group, (3) selenium + ischemia group, (4) melatonin + ischemia group, and (5) selenium + melatonin + ischemia group. AC samples were obtained. MDA and GSH levels in AC samples were evaluated. Results. MDA levels were significantly increased in ischemia groups. Selenium and melatonin supplementation resulted in reduction of MDA levels and significant increase in GSH values. Discussion. Increased lipid peroxidation associated with ischemia of the anterior segment has been prevented by selenium and melatonin supplementation. This trial is registered with ClinicalTrials.gov NCT04005222.
Successful Conservative Treatment of an Elderly Patient with Corrosive Proctocolitis
Authors: Eurboonyanun Chalerm , Ruangwannasak Somchai , Eurboonyanun Kulyada , Sripanuskul Anan
Published: December 2019

Corrosive proctocolitis has occurred after accidental contamination of endoscopes in most patients. But accidental administration of corrosive agents for bowel cleansing can occur. The agents implicated for chemical colitis is 15% hydrochloric acid and 2% ethoxylated alcohol. We present a case of corrosive proctocolitis, present with anal pain and bloody diarrhea. Endoscopy revealed edema, erythema, and friability of the colonic mucosa. An experience of successful nonoperative treatments has been demonstrated.
Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin Lymphoma
Authors: Chen Robert , Herrera Alex F. , Hou Jessie , Chen Lu , Wu Jun , Guo Yuming , Synold Timothy W. , Ngo Vu N. , Puverel Sandrine , Mei Matthew , Popplewell Leslie , Yi Shuhua , Song Joo Y. , Tao Shu , Wu Xiwei , Chan Wing C. , Forman Stephen J. , Kwak Larry W. , Rosen Steven T. , Newman Edward M.
Published: December 2019

Purpose:

In classical Hodgkin lymphoma, the malignant Reed–Sternberg cells express the cell surface marker CD30. Brentuximab vedotin is an antibody–drug conjugate (ADC) that selectively delivers a potent cytotoxic agent, monomethyl auristatin E (MMAE), to CD30-positive cells. Although brentuximab vedotin elicits a high response rate (75%) in relapsed/refractory Hodgkin lymphoma, most patients who respond to brentuximab vedotin eventually develop resistance.

Patients and Methods:

We developed two brentuximab vedotin–resistant Hodgkin lymphoma cell line models using a pulsatile approach and observed that resistance to brentuximab vedotin is associated with an upregulation of multidrug resistance-1 (MDR1). We then conducted a phase I trial combining brentuximab vedotin and cyclosporine A (CsA) in patients with relapsed/refractory Hodgkin lymphoma.

Results:

Here, we show that competitive inhibition of MDR1 restored sensitivity to brentuximab vedotin in our brentuximab vedotin–resistant cell lines by increasing intracellular MMAE levels, and potentiated brentuximab vedotin activity in brentuximab vedotin–resistant Hodgkin lymphoma tumors in a human xenograft mouse model. In our phase I trial, the combination of brentuximab vedotin and CsA was tolerable and produced an overall and complete response rate of 75% and 42% in a population of patients who were nearly all refractory to brentuximab vedotin.

Conclusions:

This study may provide a new therapeutic strategy to combat brentuximab vedotin resistance in Hodgkin lymphoma. This is the first study reporting an effect of multidrug resistance modulation on the therapeutic activity of an ADC in humans. The expansion phase of the trial is ongoing and enrolling patients who are refractory to brentuximab vedotin to confirm clinical activity in this population with unmet need.
The Relationship between Phonological Processing and Emergent Literacy Skills in Arabic-Speaking Kindergarten Children
Authors: Afsah Omayma
Published: December 2019

Introduction: Children with weak emergent literacy skills are at risk for later reading problems. The majority of research on the relationship between phonological processing and emergent literacy has been conducted on children who speak English and European languages. The aim of the current study was to address the relationship between phonological processing and emergent literacy skills in Arabic-speaking Egyptian children. Methods: A cross-sectional correlational study was conducted on a sample of 50 typically developing kindergarten children in the age range from 4 years 6 months to 6 years 5 months. Children were subjected to assessment of both phonological processing and emergent literacy using a specially constructed test battery in Arabic. Results: A highly significant positive correlation was found between total scores of phonological processing and of emergent literacy tests. Both isolating final phonemes and rapid naming were the best predictors of emergent literacy. Conclusions: Phonological processing skills are important prerequisites for the development of emergent literacy skills in Arabic-speaking children. The designed test battery proved to be both valid and reliable and can be used as a screening tool for the identification of children at risk of later reading problems.
Psychotherapeutisches Arbeiten in Palliative Care
Authors: Gramm Jan , Trachsel Manuel , Berthold Daniel
Published: December 2019

In Palliative Care arbeiten multiprofessionell zusammengesetzte Teams für die Verbesserung oder Erhaltung der Le­bensqualität von schwerstkranken Patienten und ihren Fa­milien. Klinischen Psychologen und approbierten Psychotherapeuten kommt in diesem Feld ein vielfältiges Spektrum von Aufgaben zu, das von der präventiven und supportiven Arbeit bis hin zum psychotherapeutischen Wirken im enge­ren Sinne reicht. Auch wenn die Palliativversorgung bislang vielerorts noch keine bedarfsgerechte Begleitung durch Psychologen und Psychotherapeuten leistet, sind entspre­chende Entwicklungen deutlich festzustellen. Ziel des vorliegenden Beitrags ist es, einen Überblick über Palliative Care als Anwendungsfeld psychologischer und psychotherapeutischer Interventionen zu geben. Nach einer Skizzierung der relevanten Grundzüge von Palliative Care erfolgt eine Darstellung psychologischer und psychotherapeutischer Themen, subdiagnostischer Befunde sowie psychischer Störungen in der Palliativversorgung. Schließlich soll eine Übersicht psychologischer und psychotherapeutischer Interventionen in Palliative Care gegeben werden.
Analysis of Factors Influencing the Prognostic Significance of Hyponatremia in Peritoneal Dialysis Patients
Authors: Bravo González-Blas Luis , García-Gago Leticia , Astudillo-Jarrín Daniela , Rodríguez-Magariños Catuxa , López-Iglesias Antía , García Falcón Teresa , Rodríguez-Carmona Ana , Pérez Fontán Miguel
Published: December 2019

Background: The evidence linking low serum sodium levels with the risk of mortality in peritoneal dialysis (PD) patients is controversial. Considering the different mechanisms contributing to hyponatremia in these patients, it is conceivable that the prognostic significance of this factor may vary, according to the clinical setting. Methods: Following a retrospective, observational design, we analyzed the association between hyponatremia and mortality in 748 patients incident on PD. We applied multivariate strategies of analysis, with the main objective of identifying subgroups of patients in whom hyponatremia could sustain different degrees of association with mortality (main outcome variable). For this purpose, we performed preliminary analyses to: (1) disclose predictors of serum sodium levels before and after (mean of first 3 months) initiation of PD (main study variable) and (2) investigate the overall prognostic significance of hyponatremia, in our patients. Results: Comorbidity, hypoalbuminemia, and lower glomerular filtration rate (GFR) were main predictors of hyponatremia. Use of icodextrin was another inverse correlate of serum sodium, and the only consistent predictor of a decline of natremia, once PD was started. Multivariate analysis confirmed early hyponatremia as an independent marker of survival. However, stratified analyses showed that this association was most apparent in specific subsets, namely, hypoalbuminemic, more anemic patients with higher baseline levels of GFR and C-reactive protein and faster peritoneal solute transport rates. Other factors potentially reinforcing the prognostic significance of hyponatremia included lower lean body mass levels, nonprescription of renin-angiotensin-aldosterone system antagonists, and use of icodextrin-based PD solution. On the contrary, baseline overhydration or categorization by classic predictors of mortality (age, comorbidity, diabetes) did not appear to influence the risk pattern associated with lower serum sodium levels. Conclusions: Our results suggest that hyponatremia performs as a consistent correlate of the risk of mortality mainly in PD patients manifesting direct or indirect signs of inflammation and wasting, while this association is not apparently linked to the presence of overhydration or nominal, preexisting comorbid conditions.
Taxonomic revision of Cylindera Westwood, 1831 subgenus Parmecus Motschulsky, 1864 stat. rest., stat. nov. (Coleoptera: Carabidae: Cicindelinae) with the description of one new species from Yunnan Province, China
Authors: MATALIN ANDREY V.
Published: December 2019

Within the Asiatic tiger beetle fauna, Parmecus Motschulsky, 1864 stat. rest., stat. nov., is reestablished as a subgenus of Cylindera Westwood, 1831 with Cylindera (Parmecus) dromicoides (Chaudoir, 1852), as its type species, and the lectotype and paralectotypes of Cicindela dromicoides Chaudoir, 1852 are designated as well. Two other species are included, Cylindera (Parmecus) armandi (Fairmaire, 1886), from the Himalayan Region, and Cylindera (Parmecus) mosuoa, sp. nov., from Yunnan, China. Cylindera (Parmecus) as a subgenus is characterized, a key to identify its species is provided, and its species composition is discussed. Cylindera (Parmecus) dromicoides (Chaudoir, 1852) is newly recorded from Pakistan and the Indian state of Jammu and Kashmir, while Cylindera (Parmecus) armandi (Fairmaire, 1886) is recorded for the first time from the Chinese province of Sichuan. The records of C. armandi from Bhutan, as well as C. dromicoides from Yunnan Province (China) are rejected due to erroneous identifications.
A new deepwater gurnard of the genus Pterygotrigla (Scorpaeniformes: Triglidae) from the southwestern Indian Ocean
Authors: YATO TAKUJI , HEEMSTRA ELAINE
Published: December 2019

A new species of deepwater gurnard, Pterygotrigla (Otohime) madagascarensis sp. nov. is described, based on two specimens collected on the upper continental slope south of Madagascar, in the southwestern Indian Ocean. The new species belongs to the tropical Indo-Pacific subgenus Otohime in having a short rostral projection, short posttemporal spine, long opercular spine and no cleithral spine. It is most similar to P. (O.) multipunctata, and P. (O.) urashimai, in having no large blotch on the first dorsal fin, a jet-black blotch and no white ocellus on the inner pectoral-fin surface, with no scales on the breast and front of the pectoral-fin base. However, the new species differs from the latter two species by the combination of the following characters: first dorsal-fin spines 7, second dorsal-fin rays 12, dusky rays on the inner pectoral-fin surface, one row of blackish botches on second dorsal fin, and no papillae on the dorsal surface of oral cavity. A key is provided for the twelve Pterygotrigla species now in the subgenus Otohime.
Poland as a Great Borderland in a Post-Soviet World: Poetical Point of View
Authors: Vorontsova Kristina
Published: December 2019

Poland as a Great Borderland in a Post-Soviet World: Poetical Point of ViewThis paper seeks to examine the characteristics of the literary space of Poland, which occupied a middle position between the West and the USSR, with particular attention to the mechanisms of representation of Poland as a great borderland in light of the catastrophes of the 20th century. Since the dissolution of the Soviet Union, narratives have changed but the main concept of “Poland as a Great Borderland” still remains. While absorbing traditional elements, poetry in the post Soviet world uses new tools like “camp” to depict the liminality and carnival nature of the country. Alexander Anashevich’s poems are analysed as a vivid example of contemporary perceptions of this centuries-long intercultural practice. Польша как «большая граница» в постсоветском мире: поэтический взглядВ данной статье анализируются устойчивые характеристики художественного пространства Польши, которая занимала позицию медиатора между Западом и СССР. Особое внимание уделяется механизмам репрезентации Польши как пограничной территории в свете катастроф ХХ века. С распадом Советского Союза изменились нарративы, однако главный концепт «Польша как Большая граница» всё ещё остаётся неизменным. Ориентируясь на традиционные элементы, поэзия в постсоветском мире использует новые инструменты, такие как Камп, чтобы адекватно отражать лиминальную и карнавальную природу страны. Стихи Александра Анашевича в данном контексте анализируются как яркий пример современного понимания многовековых межкультурных практик. Polska jako „Wielkie Pogranicze” w przestrzeni postradzieckiej. Poetycki punkt widzenia.Artykuł ma na celu zbadanie cech przestrzeni kulturowej Polski, która swego czasu odbierana była jako ta, zajmująca pozycję mediatora pomiędzy Zachodem a ZSRR. W artykule przede wszystkim kładzie się nacisk na zbadanie mechanizmów reprezentacji Polski jako „Wielkiego Pogranicza” w świetle katastrof XX wieku. Od czasu rozpadu Związku Radzieckiego narracje uległy zmianie, ale koncepcja „Polski jako Wielkiego Pogranicza” nadal pozostaje aktualna. Choć poezja w przestrzeni postradzieckiej wciąż zwrócona jest przede wszystkim w stronę tradycyjnych dla niej form, to coraz częściej sięga ona po nowe estetyczne rozwiązania, takie jak np. Kamp, aby wskazać na liminalny i karnawałowy charakter polskiej przestrzeni kulturowej. Wiersze Aleksandra Anaszkiewicza są w artykule analizowane jako żywy przykład współczesnej percepcji tych wielowiekowych interkulturowych praktyk.
Fictional Truth, i.e. the Biographies of Literary Heroines. Book Review: Katarzyna Szumlewicz (2017). "Miłość i ekonomia w literackich biografiach kobiet". Warszawa: IBL PAN
Authors: Gać Agata
Published: December 2019

Fictional Truth, i.e. the Biographies of Literary Heroines. Book Review: Katarzyna Szumlewicz (2017). Miłość i ekonomia w literackich biografiach kobiet. Warszawa: IBL PANThis review of Love and Economics in Women's Literary Biographies by Katarzyna Szumlewicz focuses on the major issues and social functions of the theses presented in the book. Fikcyjna prawda, czyli o biografiach bohaterek literackich. Recenzja książki: Katarzyna Szumlewicz (2017). Miłość i ekonomia w literackich biografiach kobiet. Warszawa: IBL PANArtykuł jest recenzją książki Miłość i ekonomia w literackich biografiach kobiet Katarzyny Szumlewicz, w którym skupiono się na głównych założeniach oraz funkcjach społecznych zaprezentowanych twierdzeń w publikacji.
Marginal Stability of the Convective Boundary Layer
Authors: Thuburn John , Efstathiou Georgios A.
Published: December 2019

We hypothesize that the convective atmospheric boundary layer is marginally stable when the damping effects of turbulence are taken into account. If the effects of turbulence are modeled as an eddy viscosity and diffusivity, then an idealized analysis based on the hypothesis predicts a well-known scaling for the magnitude of the eddy viscosity and diffusivity. It also predicts that the marginally stable modes should have vertical and horizontal scales comparable to the boundary layer depth. A more quantitative numerical linear stability analysis is presented for a realistic convective boundary layer potential temperature profile and is found to support the hypothesis.
Illustrative Analysis of Probabilistic Sea Level Rise Hazard
Authors: Thomas Matthew A. , Lin Ting
Published: December 2019

Sea level rise results from several contributing physical processes, including ocean thermal expansion and glacier and ice sheet mass loss. Future projections of sea level remain highly uncertain due to several sources of aleatory and epistemic uncertainty. Quantifying different sources of sea level rise involves considering possible pathways of future radiative forcing and integrating models of different sea level rise processes. The probabilistic hazard analysis strategy has been proposed for combining sea level rise prediction models and climate forcing scenarios to examine sea level rise prediction uncertainty and the sources of this uncertainty. In this study we carry out an illustrative probabilistic sea level rise hazard analysis using ensembles of sea level rise predictions and emissions scenarios from the literature. This illustrative analysis allows us to estimate the probability that sea level rise will exceed a specified threshold at a given location and time and highlights how sea level rise uncertainty is sensitive to scenario inputs and sea level rise projection modeling choices. Probabilistic hazard is depicted for Earth using sea level rise hazard maps. We also demonstrate how hazard deaggregation can help us quantify the relative contributions of sea level rise sources, prediction models, and climate forcing scenarios to sea level rise hazard. The ice sheet contribution to sea level rise has a large impact on probabilistic projection of sea level rise due to the disagreements between current ice sheet models related to differences in modeling ice sheet instability.
Atmospheric River Reconnaissance Observation Impact in the Navy Global Forecast System
Authors: Stone Rebecca E. , Reynolds Carolyn A. , Doyle James D. , Langland Rolf H. , Baker Nancy L. , Lavers David A. , Ralph F. Martin
Published: December 2019

Atmospheric rivers, often associated with impactful weather along the west coast of North America, can be a challenge to forecast even on short time scales. This is attributed, at least in part, to the scarcity of eastern Pacific in situ observations. We examine the impact of assimilating dropsonde observations collected during the Atmospheric River (AR) Reconnaissance 2018 field program on the Navy Global Environmental Model (NAVGEM) analyses and forecasts. We compare NAVGEM’s representation of the ARs to the observations, and examine whether the observation–background difference statistics are similar to the observation error variance specified in the data assimilation system. Forecast sensitivity observation impact is determined for each dropsonde variable, and compared to the impacts of the North American radiosonde network. We find that the reconnaissance soundings have significant beneficial impact, with per observation impact more than double that of the North American radiosonde network. Temperature and wind observations have larger total and per observation impact than moisture observations. In our experiment, the 24-h global forecast error reduction from the reconnaissance soundings can be comparable to the reduction from the North American radiosonde network for the field program dates that include at least two flights.
Study on structure and properties of biodegradable PLA/PBAT/organic-modified MMT nanocomposites
Authors: He Hezhi , Liu Bida , Xue Bin , Zhang He
Published: December 2019

Biodegradable polymer blends were prepared by melt blending poly(lactic acid) (PLA), poly(butylene adipate- co-terephthalate) (PBAT), and organic-modified montmorillonite (MMT). The effects of MMT on the structure, morphology, thermal, and mechanical properties of the blends were thoroughly investigated. The results revealed that MMT was preferable to localize on the interface of PLA and PBAT and esterification reaction took place between organic-modified MMT and PLA/PBAT. MMT enhanced the compatibility of PLA and PBAT, accelerated crystallization, and improved the thermal stability of PLA and PBAT. In addition, MMT illustrated the reinforcing effects on PLA and PBAT in their tensile strength, especially for PBAT.
How Team Emotional Intelligence Connects to Task Performance: A Network Approach
Authors: Zhang Hui-Hua , Ding Cody , Schutte Nicola S. , Li Rui
Published: December 2019

Drawing on a social network analysis, we examined the role of social network structure (i.e., friendship network density) as a mediating factor linking team average emotional intelligence (EI) with team task performance and how this relationship is influenced by intrateam trust. The results from 97 teams (466 team members) working on student projects in a business university over a semester indicated that teams with higher average EI exhibit a higher density of friendship networks and better team task performance in contexts characterized by higher intrateam trust. The study increases our understanding of the mechanism through which EI at the team level may affect team performance and provides new insights into how team managers and members might enhance the effectiveness of project teams.
Immigrants and the ‘caring father’: Inequality in access to and utilisation of parental leave in Norway
Authors: Ellingsæter Anne Lise , Kitterød Ragni Hege , Østbakken Kjersti Misje
Published: December 2019

How do parental leave rights and interacting societal structures influence immigrant fathers’ compliance with the ‘caring father’ model—typifying Nordic welfare states? Nordic parental leave schemes differ; this study investigated the impact of the Norwegian policy. Strong, stratifying effects related to access, particularly unfavourable for non-Western immigrant fathers, were demonstrated. These effects stemmed not only from the scheme being based on work performance criteria, but also from fathers’ rights being conditioned on mothers’ economic activity. Moreover, the observed gap between eligible immigrant and native-born fathers in the take-up of the father quota (the part of leave earmarked for fathers) was explored further. The gap was associated with weaker individual resources; however, ethnic labour market segregation played a significant role. The gap narrowed with the increased duration of stay of these fathers, suggesting that adaptation processes also are involved. The analysis is based on high-quality register data of all partnered men who became fathers in Norway in 2011, following them until their child was three years old in 2014.
Oral Bruton tyrosine kinase inhibitors block activation of the platelet Fc receptor CD32a (FcγRIIA): a new option in HIT?
Authors: Goldmann Luise , Duan Rundan , Kragh Thorsten , Wittmann Georg , Weber Christian , Lorenz Reinhard , von Hundelshausen Philipp , Spannagl Michael , Siess Wolfgang
Published: December 2019

Key Points

Six different BTKi’s blocked platelet activation in blood after FcγRIIA stimulation by cross-linking, anti-CD9 antibodies, or HIT serum. Established oral irreversible and novel reversible BTKi’s may offer a new option to treat HIT.
Case-based discussion on the implications of exogenous estrogens in hemostasis and thrombosis: the hematologist’s view
Authors: Ragni Margaret V.
Published: December 2019

In the childbearing years, hormonal therapy or hormonal changes in the menstrual cycle or the puerperium may be complicated by bleeding or thrombosis; however, among women with congenital disorders of hemostasis and thrombosis, the risk of bleeding or thrombosis may be increased. In women with congenital bleeding disorders, heavy menstrual bleeding is the most common bleeding symptom, and postpartum hemorrhage occurs despite treatment. Given the limitations of current therapy and the associated medical and psychological burden in women with bleeding disorders, better treatment approaches are needed to improve health outcomes and quality of life. In women with congenital thrombotic disorders, thromboembolism may complicate exogenous hormonal therapy and endogenous hormonal change during pregnancy and procedures, but risk differs by type of thrombophilia, procedure, time at risk, and thrombosis risk factors, all of which affect management. In this article, I shall consider a case-based discussion of current issues in women with congenital bleeding and clotting disorders, including heavy menstrual bleeding in a woman with VWD, postpartum hemorrhage risk in VWD, and thrombosis risk with oocyte retrieval in a woman with factor V Leiden and past thromboembolism. The goals are to review bleeding or thrombosis risk in these cases, current data, limitations of current treatment guidelines, and areas for future study.
Management of older Hodgkin lymphoma patients
Authors: Evens Andrew M. , Carter Jordan , Loh Kah Poh , David Kevin A.
Published: December 2019

Hodgkin lymphoma (HL) in older patients, commonly defined as ≥60 years of age, is a disease for which survival rates have historically been significantly lower compared with younger patients. Older HL patients appear to have different disease biology compared with younger patients, including increased incidence of mixed cellularity histology, Epstein-Barr virus–related, and advanced-stage disease. For prognostication, several studies have documented the significance of comorbidities and functional status in older HL patients, as well as the importance of achieving initial complete remission. Collectively, selection of therapy for older HL patients should be based in part on functional status, including pretreatment assessment of activities of daily living (ADL), comorbidities, and other geriatric measures (eg, cognition, social support). Treatment of fit older HL patients should be given with curative intent, regardless of disease stage. However, attention should be paid to serious treatment-related toxicities, including risk of treatment-related mortality. Although inclusion of anthracycline therapy is important, bleomycin-containing regimens (eg, doxorubicin, bleomycin, vinblastine, dacarbazine) may lead to prohibitive pulmonary toxicity, and intensive therapies (eg, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are too toxic. Brentuximab vedotin given sequentially before and after doxorubicin, vinblastine, and dacarbazine to fit, untreated advanced-stage older HL patients was recently shown to be tolerable and highly effective. Therapy for patients who are unfit or frail because of comorbidities and/or ADL loss is less clear and should be individualized with consideration of lower-intensity therapy, such as brentuximab vedotin with or without dacarbazine. Altogether, therapy for older HL patients should be tailored based upon a geriatric assessment, and novel targeted agents should continue to be integrated into treatment paradigms.
Integrating patient-centered factors in the risk assessment of MDS
Authors: Buckstein Rena J.
Published: December 2019

Myelodysplastic syndromes are clonal myeloid neoplasms that primarily present in older adults. Although leukemia develops in approximately 25% to 30% of individuals, the significantly shortened survival in this population is attributed more commonly to nonleukemic causes. The current prognostic scoring systems for leukemia and overall survival based on disease characteristics are becoming increasingly sophisticated and accurate with the incorporation of molecular data. The addition of patient-related factors such as comorbidity, disability, frailty, and fatigue to these new models may improve their predictive power for overall survival, treatment toxicity, and health care costs. To improve the generalizability of clinical trial results to the real world, geriatric assessment testing should become a standard of care in MDS clinical trials.
Inflammatory bone marrow microenvironment
Authors: Leimkühler Nils B. , Schneider Rebekka K.
Published: December 2019

Self-renewing hematopoietic stem cells and their progeny, lineage-specific downstream progenitors, maintain steady-state hematopoiesis in the bone marrow (BM). Accumulating evidence over the last few years indicates that not only primitive hematopoietic stem and progenitor cells (HSPCs), but also cells defining the microenvironment of the BM (BM niche), sense hematopoietic stress signals. They respond by directing and orchestrating hematopoiesis via not only cell-intrinsic but also cell-extrinsic mechanisms. Inflammation has many beneficial roles by activating the immune system in tissue repair and as a defense mechanism. However, chronic inflammation can have detrimental effects by stressing HSPCs, leading to cell (DNA) damage resulting in BM failure or even to leukemia. Emerging data have demonstrated that the BM microenvironment plays a significant role in the pathogenesis of hematopoietic malignancies, in particular, through disrupted inflammatory signaling, specifically in niche (microenvironmental) cells. Clonal selection in the context of microenvironmental alterations can occur in the context of toxic insults (eg, chemotherapy), not only aging but also inflammation. In this review, we summarize mechanisms that lead to an inflammatory BM microenvironment and discuss how this affects normal hematopoiesis. We pay particular attention to the process of aging, which is known to involve low-grade inflammation and is also associated with age-related clonal hematopoiesis and potentially malignant transformation.
Optimizing cord blood selection
Authors: Ruggeri Annalisa
Published: December 2019

Nowadays a donor can be found for virtually all patients in need of an allogeneic stem cell transplantation, and the decision whether to use a matched or mismatched unrelated donor, an unrelated donor for umbilical cord blood transplantation (UCBT), or a haploidentical donor depends not only on the availability of the donor but also on patient-, disease-, and center-related factors. This paper summarizes the recent criteria in the selection of cord blood unit, including the cell dose requirement and the HLA typing for the optimal donor choice. The main strategies to optimize the results of UCBT, the conditioning regimens, and the use of antithymocyte globulin and the other platforms of graft-versus-host disease prophylaxis are discussed. The paper describes the results of UCBT in children and adults with malignant and nonmalignant diseases and the comparative analysis with other donor type and stem cell sources. Emerging strategies, focusing on the different platforms of ex vivo expansion and the new applications using cord blood stem cell, are also examined.
The growing landscape of FLT3 inhibition in AML
Authors: Smith Catherine C.
Published: December 2019

Midostaurin and gilteritinib are FLT3 inhibitors that have been recently approved for use in FLT3-mutant acute myeloid leukemia (AML). These approved drugs represent a new standard of care for patients with FLT3 mutations in both the first-line and salvage settings. The success of midostaurin used in combination with induction chemotherapy has prompted exploration of newer, more potent and targeted inhibitors (including gilteritinib) in the first-line setting in combination with chemotherapy. At the same time, the success of gilteritinib and other newer FLT3 inhibitors as monotherapy in the salvage setting has been tempered by the development of resistance because of diverse mechanisms. Investigational strategies that incorporate FLT3 inhibitors in combination with hypomethylating agents and as maintenance therapy after allogeneic stem cell transplantation have shown promise. Other novel combination strategies are also undergoing clinical investigation. In this article, we review the current landscape of approved and investigational FLT3 inhibitors in AML, including the current standard of care and investigational strategies.
Myeloma: next generation immunotherapy
Authors: Cohen Adam D.
Published: December 2019

The course of multiple myeloma (MM) from initial diagnosis to a relapsed/refractory state is characterized by acquisition of drug resistance as well as progressive immunologic dysfunction. Despite this, however, a number of novel therapies that work in part or solely via immune stimulation are in development for MM, with promising early clinical results. Several new whole-cell or multiepitope vaccine approaches are demonstrating immunologic efficacy in smoldering MM or as posttherapy consolidation, with trials ongoing to see whether this translates into delayed progression or elimination of minimal residual disease. Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibition in combination with immunomodulatory drugs demonstrated excessive toxicity in randomized trials; however, antibodies targeting PD-1/PD-L1 and other checkpoint molecules continue to be explored in combination with tumor-targeted antibodies and other T cell–directed therapies. B-cell maturation antigen (BCMA) has emerged as the next big antigen target, with multiple BCMA-specific antibody-drug conjugates (ADCs) and T cell–directed bispecific antibodies/bispecific therapeutic engagers (BiTEs) entering the clinic. In initial trials, the ADC GSK2857916 and the BiTE AMG 420 have demonstrated high response rates in relapsed/refractory patients, with depth and durability of responses that may end up rivaling chimeric antigen receptor T-cell therapies. These agents have unique toxicities that require close monitoring, but they are moving forward in larger registration studies and in combination with standard MM agents. Additional ADCs and bispecific antibodies targeting BCMA and other surface antigens (eg, CD38, CD46, CD48, FcRH5, and G protein–coupled receptor, class C group 5 member D) are moving forward in phase 1 trials and may provide even more options for MM patients.
Evidence-Based Minireview: Mortality and thrombosis in patients receiving prothrombin complex concentrates or andexanet alfa for the management of direct oral factor Xa inhibitor–associated major bleeding
Authors: Kimpton Miriam , Siegal Deborah M.
Published: December 2019

A 77-year-old man with atrial fibrillation and a CHA2DS2Vasc score of 6 for hypertension, age, diabetes, and previous stroke is brought to the emergency department with decreased level of consciousness. He is anticoagulated with rivaroxaban (a direct oral factor Xa inhibitor [FXaI]) and received his last dose about 4 hours before presentation. Urgent computed tomography of the head shows intracerebral hemorrhage. Because of his previous stroke, the patient’s family is concerned about treating the bleed with pharmacological agents that may increase the risk of stroke. What are the risks of thrombosis and mortality related to the use of prothrombin complex concentrates (PCCs) and andexanet alfa for patients with direct oral FXaI-associated major bleeding?
Evidence-Based Minireview: Does achieving MRD negativity after initial therapy improve prognosis for high-risk myeloma patients?
Authors: Sidana Surbhi , Manasanch Elisabet
Published: December 2019

You are evaluating a 47-year-old man with revised international staging system stage III myeloma who recently underwent an autologous stem cell transplant after receiving 6 cycles of carfilzomib, lenalidomide, and dexamethasone for newly diagnosed disease. Fluorescence in situ hybridization testing at initial presentation also revealed t(4;14). On day 100 evaluation after transplant, he has achieved a stringent complete response. Two-tube, 8-color advanced flow cytometry with a sensitivity of 10−5 shows no minimal residual disease. Whole-body positron emission tomography/computed tomography scan shows resolution of all fluorodeoxyglucose avid uptake seen at diagnosis. The patient asks you how these test results impact his prognosis and whether this overcomes his baseline high risk from t(4;14)?
Clonal dynamics in chronic lymphocytic leukemia
Authors: Gutierrez Catherine , Wu Catherine J.
Published: December 2019

Chronic lymphocytic leukemia has a highly variable disease course across patients, thought to be driven by the vast inter- and intrapatient molecular heterogeneity described in several large-scale DNA-sequencing studies conducted over the past decade. Although the last 5 years have seen a dramatic shift in the therapeutic landscape for chronic lymphocytic leukemia, including the regulatory approval of several potent targeted agents (ie, idelalisib, ibrutinib, venetoclax), the vast majority of patients still inevitably experience disease recurrence or persistence. Recent genome-wide sequencing approaches have helped to identify subclonal populations within tumors that demonstrate a broad spectrum of somatic mutations, diverse levels of response to therapy, patterns of repopulation, and growth kinetics. Understanding the impact of genetic, epigenetic, and transcriptomic features on clonal growth dynamics and drug response will be an important step toward the selection and timing of therapy.