bluuebunny/crossref_metadata_2025 huggingface dataset:
Aggregated multi-criteria model of enterprise management engineering, taking into account the social priorities of the region
Authors: Bondarenko Yu V , Sviridova T A , Averina T A
Published: June 2019

The article is devoted to the development of an aggregated multi-criteria model of enterprise management engineering. The basis of the proposed approach is the understanding of the significance of a modern engineering enterprise not only for the economic, but also the social development of the region. The article focuses on the social priorities of the region in creating new jobs and increasing nominal wages at the enterprises of the machine-building complex. The model takes into account the main economic dependencies of the operation of the enterprise, as well as restrictions on the achievement of the values of the labor force required for the region and the average nominal wage. As the criteria of optimality, the maximization of the total profit for the period of profit, taking into account the profit tax, was chosen; the maximization of the minimum in time of return on capital (ROA) was taken. The software implementation and discussion of the calculation results confirmed the practical significance of the research carried out for the management of the region and the machine-building enterprise, and also outlined ways for its further improvement.
Logistics technologies in mechanical engineering complex: the prospects for outsourcing applying
Authors: Freidman O A , Malanina Yu N
Published: June 2019

The current state of the mechanical engineering complex of Russia requires the application of new industry process management technologies. In this regard, we consider the technologies of the logistic approach associated with reducing the costs distribution in material resource flow management. One of these technologies is applying of logistics outsourcing system into the external logistics system of mechanical engineering enterprises.
Identification of logical patterns for classification of EEE in space application
Authors: Masich I S , Orlov V I
Published: June 2019

The study deals with evaluation of reliability of onboard equipment on the basis of the additional screening tests and the estimated factory tests. In addition to using a statistical approach to solve this problem, the interest is a method for estimating the reliability of onboard equipment using machine learning and data mining methods. Due to the specifics of the task, it is proposed to use classification algorithms based on rules (logical classification algorithms).
Reproduction of innovative potential as a result of rocket-space industry enterprises innovative activity
Authors: Erygin Y V , Erygina L V , Votintsev R V , Shumakov F P
Published: June 2019

The strategic significance of the output products defines advantage of innovative rocket-space industry activity. In order to implement such an activity innovation potential is needed. Its formation is carried out both on the basis of resource and strategic approaches. There appear difficulties connected with the specific aspects of rocket-space industry enterprises in the course of innovative activity determination. Permanent changes of external and internal conditions cause changes of goal-setting and requirements to innovative potential. The research reproduction of innovative potential as a criterion will allow defining current efficiency of rocket-space industry enterprises innovative activity.
Plasma Aldosterone After Seated Saline Infusion Test Outperforms Captopril Test at Predicting Clinical Outcomes After Adrenalectomy for Primary Aldosteronism
Authors: Wu Che-Hsiung , Wu Vincent , Yang Ya-Wen , Lin Yen-Hung , Yang Shao-Yu , Lin Po-Chih , Chang Chin-Chen , Tsai Yao-Chou , Wang Shuo-Meng ,   TAIPAI group, Wu Vin-Cent , Wu Che-Hsiung , Hu Ya-Hui , Kiaw Leay , Chang Chia-Hui , Chang Ya-Li , Tsai Yao-Chou , Yu Chih-Chin , Lin Yen-Hung , Chan Chieh-Kai , Lin Jui-Hsiang , Wang Wei-Jie , Ho Yi-Luwn , Chang Hung-Wei , Lin Lian-Yu , Hu Fu-Chang , Chang Chin-Chen , Liu Kao-Lang , Wang Shuo-Meng , Huang Kuo-How , Jeff Chueh Shih-Chieh , Liao Shih-Cheng , Lu Ching-Chu , Yen Ruoh-Fang , Wu Kwan-Dun
Published: June 2019

OBJECTIVE

The saline infusion test (SIT) and the captopril test (CT) are widely used as confirmatory tests for primary aldosteronism (PA). We hypothesized that post-SIT and post-CT plasma aldosterone concentrations (PAC) indicate the severity of aldosterone-producing adenoma (APA) and might predict clinical outcome.

METHODS

We recruited 216 patients with APA in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry who received both seated SIT and CT as confirmatory tests. The data of 143 patients who underwent adrenalectomy with complete follow-up after diagnosis were included in the final analysis. We determined the proportion of patients achieving clinical success in accordance with the Primary Aldosteronism Surgical Outcome consensus. Logistic regression analysis was conducted to identify preoperative factors associated with cure of hypertension.

RESULTS

Complete clinical success was achieved in 48 (33.6%) patients and partial clinical success in 59 (41.2%) patients; absent clinical success was seen in 36 (25.2%) of 143 patients. Post-SIT PAC but not post-CT PAC was independently associated with clinical outcome. Higher levels of post-SIT PAC had a higher likelihood of clinical benefit (complete plus partial clinical success; odds ratio = 1.04 per ng/dl increase, 95% confidence interval = 1.01, 1.06; P = 0.004). Patients with post-SIT PAC > 25 ng/dl were more likely to have a favorable clinical outcome after adrenalectomy. This cutoff value translated into a positive predictive value of 86.0%.

CONCLUSIONS

We suggest that post-SIT PAC is a better predictor than post-CT PAC for clinical success in PA post adrenalectomy.
Critical microRNAs and regulatory motifs in cleft palate identified by a conserved miRNA–TF–gene network approach in humans and mice
Authors: Li Aimin , Jia Peilin , Mallik Saurav , Fei Rong , Yoshioka Hiroki , Suzuki Akiko , Iwata Junichi , Zhao Zhongming
Published: June 2019

Cleft palate (CP) is the second most common congenital birth defect. The etiology of CP is complicated, with involvement of various genetic and environmental factors. To investigate the gene regulatory mechanisms, we designed a powerful regulatory analytical approach to identify the conserved regulatory networks in humans and mice, from which we identified critical microRNAs (miRNAs), target genes and regulatory motifs (miRNA–TF–gene) related to CP. Using our manually curated genes and miRNAs with evidence in CP in humans and mice, we constructed miRNA and transcription factor (TF) co-regulation networks for both humans and mice. A consensus regulatory loop (miR17/miR20a–FOXE1–PDGFRA) and eight miRNAs (miR-140, miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-451a and miR-92a) were discovered in both humans and mice. The role of miR-140, which had the strongest association with CP, was investigated in both human and mouse palate cells. The overexpression of miR-140-5p, but not miR-140-3p, significantly inhibited cell proliferation. We further examined whether miR-140 overexpression could suppress the expression of its predicted target genes (BMP2, FGF9, PAX9 and PDGFRA). Our results indicated that miR-140-5p overexpression suppressed the expression of BMP2 and FGF9 in cultured human palate cells and Fgf9 and Pdgfra in cultured mouse palate cells. In summary, our conserved miRNA–TF–gene regulatory network approach is effective in detecting consensus miRNAs, motifs, and regulatory mechanisms in human and mouse CP.
Sequencing data discovery with MetaSeek
Authors: Hoarfrost Adrienne , Brown Nick , Brown C Titus , Arnosti Carol
Published: June 2019

Sequencing data resources have increased exponentially in recent years, as has interest in large-scale meta-analyses of integrated next-generation sequencing datasets. However, curation of integrated datasets that match a user’s particular research priorities is currently a time-intensive and imprecise task. MetaSeek is a sequencing data discovery tool that enables users to flexibly search and filter on any metadata field to quickly find the sequencing datasets that meet their needs. MetaSeek automatically scrapes metadata from all publicly available datasets in the Sequence Read Archive, cleans and parses messy, user-provided metadata into a structured, standard-compliant database and predicts missing fields where possible. MetaSeek provides a web-based graphical user interface and interactive visualization dashboard, as well as a programmatic API to rapidly search, filter, visualize, save, share and download matching sequencing metadata.

Availability and implementation

The MetaSeek online interface is available at https://www.metaseek.cloud/. The MetaSeek database can also be accessed via API to programmatically search, filter and download all metadata. MetaSeek source code, metadata scrapers and documents are available at https://github.com/MetaSeek-Sequencing-Data-Discovery/metaseek/.
Evolutionary and ecological forces underlying ontogenetic loss of decoy coloration
Authors: Watson Charles M , Degon Zachariah , Krogman William , Cox Christian L
Published: June 2019

Predator-based selection has resulted in the repeated evolution of a variety of antipredator traits. Despite the effectiveness of these traits, some species experience shifts or even complete loss of antipredator traits during development. The evolutionary forces that favour such a transition are poorly understood. We sought to comprehend the role of predator-based selection and organismal factors underlying developmental loss of antipredator traits by focusing on decoy coloration in skink lizards. To this end, we studied the ontogenetic loss of decoy tail coloration in three Nearctic skink species. We performed natural history collection surveys and clay-model studies on predation to determine the organismal determinants of decoy coloration (body size and energy content of the tail) and predation based upon size and decoy coloration. We found that decoy coloration was lost during development at a similar size in all three species. Although predation rates on juvenile models were similar for both uniform brown and decoy models, predation rates on adult models with decoy coloration were much higher than those on non-decoy adult models. Overall, our results suggest that predator-based selection is an important factor driving the ontogenetic loss of decoy coloration at similar sizes across these species and might be generalizable to other antipredator traits.
Jumping through the hoops: the challenges of daffodil (Narcissus) classification
Authors: Könyves Kálmán , David John , Culham Alastair
Published: June 2019

Hoop-petticoat daffodils are a morphologically congruent group comprised of two distinct lineages in molecular phylogenetic trees of Narcissus. It is possible that the morphological similarity is a product of both historic and current low-level gene flow between these lineages. For the first time, we report population sampling from across the entire range of distribution covering the Iberian Peninsula and Morocco. In total, 455 samples were collected from 59 populations. Plastid DNA sequences of matK and ndhF were generated alongside 11 microsatellite loci to permit comparison between plastid and nuclear lineage histories. The plastid DNA phylogenetic tree was highly congruent with previous molecular studies and supported the recognition of these two lineages of hoop-petticoat daffodils as separate sections. Assignment of samples to sections sometimes differed between plastid DNA and (nuclear) microsatellite data. In these cases, the taxa had previously been the focus of dissent in taxonomic placement based on morphology. These discrepancies could be explained by hybridization and introgression among the two lineages during the evolution of hoop-petticoat daffodils, and shows that placement of species in sections is dependent on the source of data used. This study underlines the complex evolutionary history of Narcissus and highlights the discrepancies between floral morphology and phylogeny, which provides a continuing challenge for the systematics of Narcissus.
Patient-reported outcome measures as a new application in the Swedish Renal Registry: health-related quality of life through RAND-36
Authors: Pagels Agneta A , Stendahl Maria , Evans Marie
Published: June 2019

Background

Although patient-reported outcome measures (PROMs) are gaining increased interest in developing health care quality and are a useful tool in person-centered care, their use in routine care is still limited. The aim of this study is to describe the implementation and initial results of PROMs via the Swedish Renal Registry (SRR) on a national level.

Methods

After testing and piloting the electronic PROM application, nationwide measures were carried out in 2017 for completing the RAND-36 questionnaire online or by paper in a wide range of chronic kidney disease (CKD) patients (Stages 3–5, dialysis and transplantation) through the SRR. Cross-sectional results during the first year were analyzed by descriptive statistics and stratified by treatment modality.

Results

A total of 1378 patients from 26 of 68 renal units (39%) completed the questionnaire. The response rate for all participating hemodialysis units was 38.9%. The CKD patients had an impaired health profile compared with a Swedish general population, especially regarding physical functions and assessed general health (GH). Transplanted patients had the highest scores, whereas patients on dialysis treatment had the lowest scores. The youngest age group assessed their physical function higher and experienced fewer physical limitations and less bodily pain than the other age groups but assessed their GH and vitality (VT) relatively low. The oldest age group demonstrated the lowest health profile but rated their mental health higher than the other age groups. The older the patient, the smaller the difference compared with persons of the same age in the general population.

Conclusions

Nationwide, routine collection of PROMs is feasible in Sweden. However, greater emphasis is needed on motivating clinical staff to embrace the tool and its possibilities in executing person-centered care. CKD patients demonstrate impaired health-related quality of life, especially regarding limitations related to physical problems, GH and VT/energy/fatigue.
Risk factors for chylothorax and persistent serous effusions after congenital heart surgery
Authors: Raatz Anna , Schöber Martin , Zant Robert , Cesnjevar Robert , Rüffer André , Purbojo Ariawan , Dittrich Sven , Alkassar Muhannad
Published: June 2019

OBJECTIVES

This study evaluated the various risk factors for chylothorax and persistent serous effusions (>7 days) after congenital heart surgery and developed equations to calculate the probability of their occurrence.

METHODS

We performed a retrospective review of different medical databases at the University Hospital of Erlangen between January 2014 and December 2016. Full model regression analysis was used to identify risk factors, and prediction algorithms were set up to calculate probabilities. Discriminative power of the models was checked with the help of C-statistics.

RESULTS

Of 745 operations on 667 patients, 68 chylothoraxes (9.1%) and 125 persistent pleural effusions (16.8%) were diagnosed. Lowest temperature [P = 0.043; odds ratio (OR) 0.899], trisomy 21 (P = 0.001; OR 5.548), a higher vasoactive inotropic score on the day of surgery (P = 0.001; OR 1.070) and use of an assist device (P = 0.001; OR 5.779) were significantly associated with chylothorax. Risk factors for persistent serous effusions were a given or possible involvement of the aortic arch during the operation (P = 0.000; OR 3.982 and 2.905), univentricular hearts (P = 0.019; OR 2.644), a higher number of previous heart operations (P = 0.014; OR 1.436), a higher vasoactive inotropic score 72 h after surgery (P = 0.019; OR 1.091), a higher central venous pressure directly after surgery (P = 0.046; OR 1.076) and an aortic cross-clamp time >86 min (P = 0.023; OR 2.223), as well as use of an assist device (P = 0.002; OR 10.281). The prediction models for both types of effusions proved to have excellent discriminative power.

CONCLUSIONS

Persistent serous effusion is associated with a higher vasoactive inotropic score 72 h after surgery, an aortic cross-clamp time >86 min and elevated central venous pressure directly after surgery, which, in combination, potentially indicate cardiac stress. The developed logistic algorithm helps to estimate future likelihood.
Management and outcomes of patients with Crohn’s disease with first vs multiple surgeries: results from the PRACTICROHN study
Authors: Iborra Marisa , Juliá Berta , Martín Arranz Maria Dolores , Barreiro-de Acosta Manuel , Gutiérrez Ana , García-Sánchez Valle , Taxonera Carlos , Gisbert Javier P , Cea-Calvo Luis , Domènech Eugeni
Published: June 2019

Background

Surgery in Crohn’s disease (CD) may be associated with poor prognosis and clinical and surgical recurrence. The aim of this study was to describe and compare the post-operative management and outcomes of patients with CD who underwent first vs recurrent surgeries.

Methods

Observational study that included adult CD patients from 26 Spanish hospitals who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010. Data were retrospectively collected from the medical records.

Results

Data from 314 patients were analysed, of whom 262 (83%) underwent first surgery and 52 (17%) referred to previous CD surgeries. Baseline characteristics were similar between the two groups except for a higher rate of stricturing behavior at diagnosis among re-operated patients (P = 0.03). After surgery, a higher proportion of re-operated patients received prophylactic treatment with immunomodulators compared with patients with first surgery (P = 0.04). In re-operated patients, time to clinical recurrence was not associated with the fact of receiving or not prophylaxis, whereas, in patients with first surgery, recurrence-free survival was greater when prophylaxis was received (P = 0.03).

Conclusions

After surgery, a higher proportion of patients with previous surgeries received prophylactic treatment with immunomodulators compared with patients with first surgery. Although prophylactic treatment was beneficial for preventing clinical recurrence in patients operated on for the first time, it did not significantly reduce the risk of further recurrence in patients with previous surgeries. This suggests that effective prophylactic therapies are still needed in this subset of patients.
Three-dimensional numerical modelling of the drained/undrained transition for frequency-dependent elastic moduli and attenuation
Authors: Sun Chao , Tang Genyang , Zhao Jianguo , Zhao Liming , Long Teng , Li Min , Wang Shangxu
Published: June 2019

In fully fluid-saturated rocks, two common phenomena are documented both experimentally and theoretically for frequency-dependent elastic moduli and attenuation, that is, the drained/undrained transition and the relaxed/unrelaxed transition. When investigating these transitions with the forced oscillation method in the laboratory, it is crucial to consider the boundary differences between the laboratory and the underground. A 1-D poroelastic numerical model was previously established to describe these differences and their effects; however, the boundary conditions used in the model are actually different from the real experiment case, thus leading to inaccurate predication of the measurement results in a laboratory. In this paper, we established a 3-D poroelastic numerical model with a new set of boundary conditions that better represent the experiment conditions. Furthermore, the 3-D poroelastic modelling results were compared with laboratory measurements under the same boundary conditions, showing a much better fit than the 1-D model. Therefore, the 3-D model provides a more accurate and reliable approach to understand the regimes and transitions of elastic modulus dispersion and attenuation, and thus has great importance in interpreting the measurements of frequency-dependent properties of rocks in the laboratory.
Second-order consensus of multi-agent systems with mixed delays and uncertain parameters via adaptive pinning aperiodically intermittent control
Authors: Zhou Boling , Yang Yongqing , Xu Xianyun
Published: June 2019

This paper investigates the second-order consensus of multi-agent systems with mixed delays and uncertain parameters. On one hand, an adaptive pinning aperiodically intermittent control protocol is designed to make multi-agent systems reach the second-order consensus. Moreover, the intermittent control protocol can be designed to be aperiodic, which means each agent can only obtain the relative states’ information from its neighbours at a sequence of disconnected aperiodic time intervals. On the other hand, based on the assumption that delay is less than the width of communication time, some consensus criterions in the form of matrix inequalities are derived by using Halanay inequality, Jensen inequality and Schur complement. At last, a simulation example is given to illustrate the correctness of the theoretical analysis.
Mental health: in the spotlight but a long way to go
Authors: Patel Vikram
Published: June 2019

We need to radically reframe our conversations about mental health to address the massive global prevention, care and quality gaps to reduce the global burden of mental health problems. This commentary looks at mental health over the past decade and what more we need to do to tackle this priority global health issue.
A resolution calculus for MinSAT
Authors: Li Chu-Min , Xiao Fan , Manyà Felip
Published: June 2019

The logical calculus for SAT are not valid for MaxSAT and MinSAT because they preserve satisfiability but not the number of unsatisfied clauses. To overcome this drawback, a MaxSAT resolution rule preserving the number of unsatisfied clauses was defined in the literature. This rule is complete for MaxSAT when it is applied following a certain strategy. In this paper we first prove that the MaxSAT resolution rule also provides a complete calculus for MinSAT if it is applied following the strategy proposed here. We then describe an exact variable elimination algorithm for MinSAT based on that rule. Finally, we show how the results for Boolean MinSAT can be extended to solve the MinSAT problem of the multiple-valued clausal forms known as signed conjunctive normal form formulas.
Chemical abundances in the metal-intermediate GC NGC 6723
Authors: Crestani Juliana , Alves-Brito Alan , Bono Giuseppe , Puls Arthur A , Alonso-García Javier
Published: June 2019

We have performed a detailed spectral analysis of the inner halo Galactic globular cluster (GC) NGC 6723 using high-resolution (R${\approx }$ 22 000–48 000) spectra for for 11 red giant branch stars collected with MIKE (Magellan) and FEROS (MPG/ESO). This globular is located at the minimum of the bimodal metallicity distribution of GCs, which suggests that it might be an excellent transitional system between metal-intermediate and metal-rich GCs. In spite of its metal-intermediate status, it is characterized by an extended horizontal branch and by a large number of RR Lyrae stars. We investigated abundances of a variety of species, including light, $\alpha$-, Fe-peak, and neutron-capture elements. We found a mean metallicity ${}[\mathrm{Fe/H}]=-0.93 \pm 0.05$ dex and typical $\alpha$-enrichment (${}[\alpha /\mathrm{Fe}] \approx 0.39$) that follows the trend of metal-poor and metal-intermediate GCs. The same outcome applies for light metals (Na, Al), Fe-peak (V, Cr, Mn, Fe, Co, Ni, Cu) and s/r-process elements (Ba, Eu), and for the classical anticorrelation: Na–O and Mg–Al. The current findings further support the evidence that the chemical enrichment of NGC 6723 is more in line with metal-intermediate GCs and their lower metallicity counterparts, and it does not bring forward the prodrome of the metal-rich regime.
The star formation history of the Sculptor dwarf spheroidal galaxy
Authors: Bettinelli M , Hidalgo S L , Cassisi S , Aparicio A , Piotto G , Valdes F , Walker A R
Published: June 2019

We present the star formation history (SFH) of the Sculptor dwarf spheroidal galaxy based on deep g, r photometry taken with Dark Energy Camera at the Blanco telescope, focusing our analysis on the central region of the galaxy extended up to ∼3 core radii. We have investigated how the SFH changes radially, subdividing the sampled area into four regions, and have detected a clear trend of star formation. All the SFHs show a single episode of star formation, with the innermost region presenting a longer period of star formation of ∼1.5 Gyr and for the outermost region the main period of star formation is confined to ∼0.5 Gyr. We observe a gradient in the mean age which is found to increase going towards the outer regions. These results suggest that Sculptor continued forming stars after the reionization epoch in its central part, while in the peripheral region, the majority of stars probably formed during the reionization epoch and soon after its end. From our analysis, Sculptor cannot be considered strictly as a fossil of the reionization epoch.
The generalized and extended uncertainty principles and their implications on the Jeans mass
Authors: Moradpour H , Ziaie A H , Ghaffari S , Feleppa F
Published: June 2019

The generalized and extended uncertainty principles affect the Newtonian gravity and also the geometry of the thermodynamic phase space. Under the influence of the latter, the energy–temperature relation of ideal gas may change. Moreover, it seems that the Newtonian gravity is modified in the framework of the Rényi entropy formalism motivated by both the long-range nature of gravity and the extended uncertainty principle. Here, the consequences of employing the generalized and extended uncertainty principles, instead of the Heisenberg uncertainty principle, on the Jeans mass are studied. The results of working in the Rényi entropy formalism are also addressed. It is shown that unlike the extended uncertainty principle and the Rényi entropy formalism that lead to the same increase in the Jeans mass, the generalized uncertainty principle can decrease it. The latter means that a cloud with mass smaller than the standard Jeans mass, obtained in the framework of the Newtonian gravity, may also undergo the gravitational collapse process.
Reproductive biology and ecology of the boreoatlantic armhook squidGonatus fabricii(Cephalopoda: Gonatidae)
Authors: Golikov Alexey V , Blicher Martin E , Jørgensen Lis L , Walkusz Wojciech , Zakharov Denis V , Zimina Olga L , Sabirov Rushan M
Published: June 2019

The squid Gonatus fabricii (Lichtenstein, 1818) is the most abundant pelagic cephalopod in the Arctic and the only squid to spend all of its life cycle in this region. Despite being highly abundant, its reproductive biology remains poorly known, and data on large maturing and mature specimens are especially rare. This study, based on extensive material (51 large specimens and >35,000 specimens in all), fills major gaps in the knowledge of the reproductive biology and ecology of G. fabricii. The fecundity of females ranged from 8,862 to 16,200 oocytes, with mature and late maturing specimens having between 8,862 to c. 10,000 and 11,402 oocytes, respectively. Oogenesis was synchronous, and oocyte resorption was observed; resorbed oocytes constituted up to 23.5% of fecundity. Between two to five ripe oocytes were observed, and these were 4.0–5.5 mm in diameter (maximum dimension). Males possessed between 77 and 257 spermatophores (length = 5.8–10.8 mm). Spermatophores were characterized by a cement body with well-developed collar and discs at the oral end, an ejaculatory apparatus longer than the cement body and the lack of a tapered, sharp tip to the cement body. Spermatophore size showed a uniform increase in relation to increasing male size. In newer spermatophores, the length, width and volume of the seminal reservoir also increased. Females possessed between 62 and 84 spermatangia (length = 1.8–2.6 mm); the spermatangia were present on the buccal membranes and lacked special attachment structures. Seminal receptacles were not found on the buccal membranes of females. Our findings are consistent with the hypothesis of geographically restricted spawning in G. fabricii. The study found evidence for one new breeding area in south-eastern Greenland. No differences in sizes at maturity were found between the breeding areas. Such geographically localized reproduction is relatively common in non-deep-water squids, but is much less common in deep-water squids. Localized reproduction may be especially important for G. fabricii because increased food availability in the epipelagic layers would likely increase the survival of epipelagic juveniles, with surface currents potentially aiding in their dispersal.
Increase in Invasive Group A Streptococcal Disease and Emergence of Mucoid Strains in a Pediatric Population: February–June 2017
Authors: Walker Lorne W , Montoya Lindsay , Chochua Sopio , Beall Bernard , Green Michael
Published: June 2019

Background

Infection with group A Streptococcus (GAS) can cause severe systemic and locally invasive disease. Invasive group A streptococcal (iGAS) disease incidence varies both seasonally and year-to-year, and it may exhibit clustered outbreaks. We observed an upswing in iGAS cases at a tertiary care Children’s Hospital, prompting further characterization of local iGAS disease.

Methods

Cases of iGAS disease were abstracted from the medical record by manual chart review of all positive screening tests and cultures for GAS over a 4-year span. Incidence rates per 1000 hospital admissions and per 100 positive GAS tests were calculated and compared. Selected isolates were further characterized by whole-genome sequencing.

Results

Significant year-to-year differences in per-admission iGAS incidence rate were observed in February and June, although per-positive test incidence rates were not significantly different. Whole-genome sequencing revealed 2 dominant serotypes—emm3 and emm6—with high rates of mucoid phenotype and systemic bacteremia.

Conclusions

We document a significant but transient increase in iGAS disease incidence in 2 months of 2017. Genome sequencing revealed 2 dominant serotypes associated with mucoid phenotypes and severe disease, highlighting the dynamic nature of iGAS disease pattern.
Probing the Higgs sector in the nonrelativistic domain
Authors: Zhang Zhentao
Published: June 2019

As a process that contains direct information from the Higgs self-coupling, we investigate the muon-induced Higgs pair production $\mu^-\mu^+\rightarrow HH$. We calculate the one-loop corrections to the cross section, and in the threshold region we take into account the nonperturbative contribution from the Higgs self-interactions in the final state. We point out that the Higgs pair production in the nonrelativistic domain might be a useful process for probing the Higgs sector.
The treatment of Austrian private foundations under the Ultimate Beneficial Ownership Act
Authors: Petritz Michael , Horkel-Wytrzens Cordula
Published: June 2019

As part of the implementation of the fourth Anti-Money Laundering Directive in Austria, the Wirtschaftliche Eigentümer Register Gesetz, (The Ultimate Beneficial Owner Register Act) was introduced. The main aim of this Act is to provide accurate and up-to-date information on the ultimate beneficial owner (UBO) of entities, trusts, and foundations. This information is seen as a key factor in combating money laundering and terrorist financing. Paragraph 2 of the Ultimate Beneficial Ownership Act defines the UBO, which corresponds to the definition in paragraph 3 subparagraph 6 of the Anti-Money Laundering Directive. In the case of corporate entities, ultimate ownership and control are relevant for determining the UBO. In the case of trusts and private foundations, it is not ownership and control that are relevant for determining the UBO, but the function the person has with respect to the trust/foundation. All definitions have in common that the UBO has to be a natural person. Obliged entities are required to identify and report their UBOs to the register, in the case of a breach of duty/law severe penalties apply.
Include, Individualize, and Integrate: Organizational Meta-strategies for Mature Workers
Authors: Parker Sharon K , Andrei Daniela M
Published: June 2019

In this commentary, we synthesize the literature on mature workers in organizations to support the development of an intervention-focused research program. We identify 3 broad approaches, or “meta-strategies,” which theory and research suggest organizations can use to reap the benefits associated with a mature and age-diverse workforce. “Include” involves strategies to create an inclusive climate in which mature workers are welcomed and fairly treated and is based on theories such as optimal distinctiveness theory. “Individualize” involves strategies to adapt the work to meet the individual needs and preferences of an aging workforce, such as work redesign and is based on theories about how people change over the life span. “Integrate” involves strategies to address the greater age diversity that comes with an aging workforce, such as how mentoring schemes enable younger and older workers to better learn from each other, and is based on theories such as those concerned with team diversity. We believe that this framework will help organizational decision makers to think more broadly and more proactively about how to manage, and harness the benefits of, an aging workforce. Our framework also challenges researchers to give more attention to intervention studies, including considering what configurations of strategies might be most helpful, as well as whether sequencing of strategies is important.
PF288 POPULATION PHARMACOKINETIC (POPPK) AND CONCENTRATION‐QTC ANALYSIS OF QUIZARTINIB IN PATIENTS (PTS) WITH FLT3‐ITD–POSITIVE RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML)
Authors: Kang D. , Ludwig E. , Jaworowicz D. , Huang H. , Fiedler‐Kelly J. , Cortes J. , Ganguly S. , Khaled S. , Krämer A. , Levis M. , Martinelli G. , Perl A. , Russell N. , Abutarif M. , Choi Y. , Kobayashi K. , Mendell J. , Yin O.
Published: June 2019

Background:

Quizartinib is a highly potent and selective FLT3 inhibitor with robust clinical activity in pts with R/R FLT3‐ITD AML.

Aims:

This analysis was conducted to evaluate the PopPK with quizartinib in a pooled analysis of 7 trials and to evaluate the relationship of quizartinib concentration to QTc in patients from the phase 3 QuANTUM‐R (AC220–007) study.

Methods:

The PopPK analysis included data from 585 participants enrolled in 5 phase 1 studies, 1 phase 2 study (2689‐CL‐2004), and 1 phase 3 study (QuANTUM‐R). Quizartinib was given as single or multiple doses of 20, 30, 60, and 90 mg (17.7, 26.5, 53, 79.5 mg free base). In QuANTUM‐R, the starting dose was 30 mg/day, increased to 60 mg/day after 2 weeks if QTcF was <450 ms. Patients receiving a concurrent strong CYP3A inhibitor initiated quizartinib at 20 mg/day, with an increase to 30 mg/day if QTcF was <450 ms. Concentration‐QTc analysis included only QuANTUM‐R pts (n = 226). Nonlinear mixed‐effects modeling was performed using observed quizartinib concentrations and time‐matched triplicate ECG measurements.

Results:

Only strong CYP3A inhibitor use produced a meaningful effect on quizartinib overall exposure (AUC)—an approximately 62% increase. Participant status (AML pts vs healthy participants), albumin level, and body surface area were statistically significant factors, but their effects on quizartinib AUC were <20%. QTcF increased in a concentration‐dependent manner, and the predicted mean increase at the maximum concentration of 60 mg was 21.1 ms (90% CI, 18.3–23.6 ms). Hypokalemia (serum potassium <3.5 mmol/L) was a statistically significant covariate affecting baseline QTcF, but no differences in QTcF increase would be expected at the same quizartinib concentration between patients with and those without hypokalemia.

Summary/Conclusion:

Strong CYP3A inhibitor use was the only clinically meaningful factor affecting quizartinib PK exposure. QTcF showed an exposure‐dependent increase with respect to quizartinib concentration; but no significant factors, including sex and age, were identified affecting the concentration‐QTc relationship. Results support clinical recommendation of dose reduction in pts receiving strong CYP3A inhibitors because quizartinib exposure is increased significantly in the presence of such agents.
PF316 THE CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH AGGRESSIVE LARGE CELL LYMPHOMA AND DIABETES MELLITUS
Authors: Pasvolsky O. , akirov A. , elias B. , raanani P. , gurion R. , rozovski U.
Published: June 2019

Background:

Epidemiological studies suggest that patients with diabetes mellitus (DM) are at‐risk to develop several types of cancers, including non‐Hodgkin lymphoma. Whether DM affects the clinical presentation or outcome of patients with lymphoma is unknown. Since patients with DM are prone to develop infectious complications, we hypothesize that the co‐occurrence of DM would increase the rate and/or severity of infectious complications in patients with lymphoma who receive chemotherapy.

Aims:

To describe the clinical characteristics and outcomes of patients with DM who received treatment for aggressive large cell lymphoma.

Methods:

This is a single center retrospective single center study. We included all consecutive patients who were diagnosed with aggressive large cell lymphoma and were treated at our institute between 2013 and 2017. Demographics, disease‐related and outcome data were extracted from the electronic medical records. Additional data and lab results were extracted from the hospital database. Categorical variables were compared using the χ2 or the Fischer exact test, and Mann Whitney was used to compare medians.

Results:

Between the years 2013 and 2017 we treated 226 patients with aggressive large cell lymphoma, most (n = 219, 96%) with diffuse large B cell lymphoma. In this cohort 49 patients (22%) had type 2 DM. None of our patients had type 1 DM. The median age of patients with DM was 70 years, and of non‐DM patients 65 years (P = 0.001). Patients with DM tended to have higher baseline BMI values (P = 0.057), but were comparable in all other demographic characteristics. Likewise, response to therapy, relapse rates and survival outcomes were similar in patients with DM compared to non‐DM patients.

There were 133 hospital admissions due to febrile neutropenia (FN) in the entire cohort. Patients with DM had higher rates of admissions due to FN (P = 0.004). The admission rate in patients with DM remained higher after age‐matched subgroup analysis (P = 0.005). Yet, the duration of hospitalizations and number of admissions to the ICU were similar in patients with or without DM. In patients with DM, improved glycemic control during FN hospitalizations was associated with shorter hospital duration (P = 0.007). However, Hemoglobin A1C levels were not associated with increased risk for FN or infectious complications.

Summary/Conclusion:

Patients with aggressive large cell lymphoma and DM have higher rates of hospitalizations due to FN. In this high risk population, perhaps more aggressive measures should be made to avoid infectious complications. Furthermore, our data suggests that improved glycemic control during hospitalization is associated with shorter length of hospitalization due to FN in patients with DM.
PF333 RISK OF BLEEDING COMPLICATIONS AND ATRIAL FIBRILLATION ASSOCIATED WITH IBRUTINIB TREATMENT: A SYSTEMATIC REVIEW AND META‐ANALYSIS
Authors: Pellegrini L. , Novak U. , Andres M. , Nagler M.
Published: June 2019

Background:

The use of ibrutinib is rapidly increasing because of its high potency to treat chronic lymphocytic leukaemia and other lymphoproliferative disorders. The application is however hampered by major adverse events such as bleeding complications and atrial fibrillation. The frequency and predictors of these adverse events are unknown.

Aims:

We aimed to study the frequency and predictors of bleeding complications and atrial fibrillation in patients treated with ibrutinib.

Methods:

Following a prespecified protocol, we systematically searched the literature for case series, cohort studies, as well as randomized controlled trials reporting on patients treated with ibrutinib using MEDLINE and EMBASE databases. We retrieved all relevant data in parallel. Methodological quality was observed using the Newcastle‐Ottawa Scale (NOS). Proportions of patients with bleeding events as well as atrial fibrillation were pooled in relevant subgroups using the binominal distribution and Freeman‐Tukey double arcsine transformation.

Results:

Among 1870 records screened, and 263 articles assessed in full‐text, 58 were finally included, comprising 4918 patients treated with ibrutinib. Methodological quality according to NOS was rated as poor to moderate. Bleeding events varied substantially with any bleedings reported between 2.8% and 78%, and major bleedings between 0% and 25% (Figure 1). New onset of atrial fibrillation was reported between 0% and 11%. Pooled estimates were 25% for any bleedings (95% confidence interval [CI] 19%, 32%); 3% for major bleedings (95% CI 2%, 4%), and 5% for atrial fibrillation (95% CI 4%, 6%). Predictors of adverse events were not apparent.

Summary/Conclusion:

Reporting of bleeding events and atrial fibrillation varied substantially among studies. These observations, in combination with the estimates obtained suggests a relevant risk of bleeding events as well as atrial fibrillation in patients treated with ibrutinib.

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PF413 CARDIAC, VASCULAR, AND HYPERTENSION SAFETY OF BOSUTINIB VS IMATINIB FOR NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA IN THE BFORE TRIAL
Authors: Brümmendorf T.H. , Gambacorti‐Passerini C. , Clark R. , Leip E. , Viqueira A. , Kota V. , Deininger M. , Cortes J.E.
Published: June 2019

Background:

Tyrosine kinase inhibitor therapy has been linked to cardiac and vascular events.

Aims:

Cardiac, vascular, and hypertension treatment‐emergent adverse events (TEAEs) with bosutinib or imatinib for newly diagnosed chronic phase chronic myeloid leukemia were analyzed.

Methods:

Patients who received ≥1 dose of bosutinib (n = 268) or imatinib (n = 265) 400 mg/day in the phase 3 BFORE trial (NCT02130557) were included. Prespecified MedDRA terms comprised the clusters of investigator assessed TEAEs. Exposure‐adjusted TEAE rate was defined as the number of patients with TEAEs / total patient‐year, where patient‐year = the sum of total time to first TEAE for patients with TEAEs and treatment duration for patients without TEAEs.

Results:

After ≥36 months of follow‐up, 65% vs 62% of patients in the bosutinib vs imatinib arm were still on treatment. Rates of TEAEs, treatment withdrawals, and drug‐related TEAEs in the clusters of interest were low in both arms (Table). The most common cardiac, vascular, and hypertension TEAEs, respectively, were sinus bradycardia (2%), angina pectoris (3%), and hypertension (7%) vs prolonged QT (3%), peripheral coldness (1%), and hypertension (9%) with bosutinib vs imatinib; corresponding grade 3/4/5 TEAE rates in the respective clusters were 3%, 3%, and 4% vs 1%, 0.4%, and 4%. Hypertension was the only grade 3/4 TEAE occurring in ≥1% of patients in either arm (4% each); 1 grade 5 TEAE each was noted for bosutinib (cardiac failure) and imatinib (cerebrovascular accident). Exposure‐adjusted rates of cardiac, vascular, and hypertension TEAEs, respectively, were 0.04, 0.03, and 0.04 vs 0.03, 0.01, and 0.04 (grade 3/4/5 only: 0.01, 0.01, and 0.02 vs 0.01, 0.002, and 0.02) for bosutinib vs imatinib.

Summary/Conclusion:

Cardiac, vascular, and hypertension TEAE rates were similarly low with bosutinib and imatinib. A majority of TEAEs were low grade and few led to treatment withdrawal.

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PF607 MAINTENANCE WITH WEEKLY CARFILZOMIB IN ELDERLY NEWLY DIAGNOSED MULTIPLE MYELOMA (IFM 2012–03)
Authors: Bobin A. , Fouquet G. , Duhamel A. , Karlin L. , Kolb B. , Tiab M. , Bourquard P. , Lenain P. , Jaccard A. , Belhadj‐Merzoug K. , Attal M. , Moreau P. , Hulin C. , Facon T. , Avet‐Loiseau H. , Leleu X.
Published: June 2019

Background:

Continuous therapy, such as maintenance, appears to be a major therapeutic change in multiple myeloma, improving response rate and overall survival. Novel agents widen the range of treatment options, but still Lenalidomide (IMIiD) is widely used in this indication. Even though usually well tolerated it remains a daily treatment, and thus can lead to some side effects on a long term basis. Carfilzomib, a second generation PI, allows interesting response rate and prolonged survival, with manageable adverse events. Nevertheless, only few clinical trials focused on its use in maintenance rather than in first or second line treatment.

Aims:

Thereforewe, we chose to study maintenance Carfilzomib for elderly newly diagnosed multiple myeloma (eNDMM).

Methods:

IFM 2012–03 is a multicenter phase I study for eNDMM (patients aged 65 years old and more) that determined the maximal tolerated dose of weekly carfilzomib, associated with melphalan and prednisone (KMP), at 70 mg/m2. The following results will concern the second phase of the study using intravenous Carfilzomib monotherapy in maintenance. K was administered at 36 mg/m2 for 13 cycles on an every 2 weeks schedule.

Results:

Thirty eNDMM were recruited in IFM 2012–03. Median age is 75, with 56% R‐ISS 2 or 3 and 11% high‐risk cytogenetic. With K weekly from 36 to 70 mg/m2, OS is reported at 93.3%, including 46.7% ≥CR; median PFS is 35.8 months and median OS was not reached.

Twenty‐two (73%) patients started K maintenance and 16 (73%) completed it. Four patients progressed and 2 stopped for AEs (renal amylosis, sensory neuropahty) during the maintenance phase. At maintenance completion, 50% were ≥CR. From the start of maintenance, in landmark analysis, median PFS is 28.1 months and the estimated 36‐months OS approximately 70%.

Summary/Conclusion:

Maintenance Carfilzomib enables deep responses as well as prolonged survival for patients over 65 years old presenting with a newly diagnosed multiple myeloma. With promising results, a fixed duration and a satisfying safety profile it could integrate new treatment strategies for ineligible to transplant NDMM. Surely patients could benefit of its efficacy in addition to simple administration modality. Further studies should still bring additional informations in order to confirm our results. Nowadays, multiple myeloma treatment landscape and clinical practice is constantly evolving leading to significant improvement for our patients.