bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure‐Response and Population Pharmacokinetic Analyses of a Novel Subcutaneous Formulation of Daratumumab Administered to Multiple Myeloma Patients
Authors: Luo Man (Melody) , Usmani Saad Z. , Mateos Maria‐Victoria , Nahi Hareth , Chari Ajai , San‐Miguel Jesus , Touzeau Cyrille , Suzuki Kenshi , Kaiser Martin , Carson Robin , Heuck Christoph , Qi Ming , Zhou Honghui , Sun Yu‐Nien , Parasrampuria Dolly A.
Published: November 2020

We report the population pharmacokinetic (PK) and exposure‐response analyses of a novel subcutaneous formulation of daratumumab (DARA) using data from 3 DARA subcutaneous monotherapy studies (PAVO Part 2, MMY1008, COLUMBA) and 1 combination therapy study (PLEIADES). Results were based on 5159 PK samples from 742 patients (DARA 1800 mg subcutaneously, n = 487 [monotherapy, n = 288; combination therapy, n = 199]; DARA 16 mg/kg intravenously, n = 255 [all monotherapy, in COLUMBA]; age, 33‐92 years; weight, 28.6‐147.6 kg). Subcutaneous and intravenous DARA monotherapies were administered once every week for cycles 1‐2, once every 2 weeks for cycles 3‐6, and once every 4 weeks thereafter (1 cycle is 28 days). The subcutaneous DARA combination therapy was administered with the adaptation of corresponding standard‐of‐care regimens. PK samples were collected between cycle 1 and cycle 12. Among monotherapy studies, throughout the treatment period, subcutaneous DARA provided similar/slightly higher trough concentrations (Ctrough) versus intravenous DARA, with lower maximum concentrations and smaller peak‐to‐trough fluctuations. The PK profile was consistent between subcutaneous DARA monotherapy and combination therapies. The exposure‐response relationship between daratumumab PK and efficacy or safety end points was similar for subcutaneous and intravenous DARA. Although the ≤65‐kg subgroup reported a higher incidence of neutropenia, no relationship was found between the incidence of neutropenia and exposure, which was attributed, in part, to the preexisting imbalance in neutropenia between subcutaneous DARA (45.5%) and intravenous DARA (19%) in patients ≤50 kg. A flat relationship was observed between body weight and any grade and at least grade 3 infections. The results support the DARA 1800‐mg subcutaneous flat dose as an alternative to the approved intravenous DARA 16 mg/kg.
Responsiveness of metallothionein and hemocyanin genes to cadmium and copper exposure in the garden snailCornu aspersum
Authors: Pedrini‐Martha Veronika , Schnegg Raimund , Schäfer Gabriela Giannina , Lieb Bernhard , Salvenmoser Willi , Dallinger Reinhard
Published: November 2020

Terrestrial gastropods express metal‐selective metallothioneins (MTs) by which they handle metal ions such as Zn2+, Cd2+, and Cu+/Cu2+through separate metabolic pathways. At the same time, they depend on the availability of sufficient amounts of Cu as an essential constituent of their respiratory protein, hemocyanin (Hc). It was, therefore, suggested that in snails Cu‐dependent MT and Hc pathways might be metabolically connected. In fact, the Cu‐specific snail MT (CuMT) is exclusively expressed in rhogocytes, a particular molluscan cell type present in the hemocoel and connective tissues. Snail rhogocytes are also the sites of Hc synthesis. In the present study, possible interactions between the metal‐regulatory and detoxifying activity of MTs and the Cu demand of Hc isoforms was explored in the edible snailCornu aspersum, one of the most common European helicid land snails. This species possesses CdMT and CuMT isoforms involved in metal‐selective physiological tasks. In addition,C. aspersumexpresses three different Hc isoforms (CaH ɑD, CaH ɑN, CaH β). We have examined the effect of Cd2+and Cu2+exposure on metal accumulation in the midgut gland and mantle ofC. aspersum, testing the impact of these metals on transcriptional upregulation ofCdMT,CuMT, and the threeHcgenes in the two organs. We found that theCuMTandCaH ɑDgenes exhibit an organ‐specific transcriptional upregulation in the midgut gland of Cu‐exposed snails. These results are discussed in view of possible interrelationships between the metal‐selective activity of snail MT isoforms and the synthesis and metabolism of Hc isoforms.
Green synthesis of 1,3,4‐oxadiazole derivatives based on N‐arylidene‐2‐(1‐oxo‐4‐(4‐phenoxyphenyl)phthalazin‐2(1H)‐yl)acetohydrazide as potential antitumor agents
Authors: Behalo Mohamed S. , El Said Ebtsam S.
Published: November 2020

Design of a new series of 1,3,4‐oxadiazole derivatives was achieved in good yield via treatment of N‐arylidene‐2‐(1‐oxo‐4‐(4‐phenoxyphenyl)phthalazin‐2(1H)‐yl)acetohydrazide with cerium (IV) ammonium nitrate as a catalyst. They can be formulated also using one‐pot reaction of 2‐(1‐oxo‐4‐(4‐phenoxyphenyl)phthalazin‐2(1H)‐yl)acetohydrazide, aromatic aldehyde and cerium (IV) ammonium nitrate in dichloromethane. The structural formulas of all synthesized products were elucidated based on their elemental and spectral analyses. In addition, MTT assay was used to evaluate antitumor activity of the synthesized molecules and some of them showed potent activity in comparison with Doxorubicin as a standard drug.
Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling
Authors: Gonzalez Esteban Alberto , Tobar Leitão Santiago Alonso , Soares Douglas dos Santos , Tavares Angela Maria Vicente , Giugliani Roberto , Baldo Guilherme , Matte Ursula
Published: November 2020

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, that codifies the alpha‐L‐iduronidase enzyme, which deficiency leads to storage of glycosaminoglycans, with multiple clinical manifestations. One of the leading causes of death in MPS I patients are cardiac complications such as cardiac valve thickening, conduction abnormalities, myocardial dysfunction, and cardiac hypertrophy. The mechanism leading to cardiac dysfunction in MPS I is not entirely understood. In a previous study, we have demonstrated that losartan and propranolol improved the cardiac function in MPS I mice. Thus, we aimed to investigate whether the pathways influenced by these drugs may modulate the cardiac remodeling process in MPS I mice. According to our previous observation, losartan and propranolol restore the heart function, without altering valve thickness. MPS I mice presented reduced activation of AKT and ERK1/2, increased activity of cathepsins, but no alteration in metalloproteinase activity was observed. Animals treated with losartan showed a reduction in cathepsin activity and restored ERK1/2 activation. While both losartan and propranolol improved heart function, no mechanistic evidence was found for propranolol so far. Our results suggest that losartan or propranolol could be used to ameliorate the cardiac disease in MPS I and could be considered as adjuvant treatment candidates for therapy optimization.
An improved cuckoo search with reverse learning and invasive weed operators for suppressing sidelobe level of antenna arrays
Authors: Lin Peng , Wang Aimin , Zhang Lin , Wu Jing , Sun Geng , Liu Lingling , Lu Lingfeng
Published: November 2020

In order to overcome some shortcomings including the premature convergence and slow convergence speed at later evolution stage of conventional cuckoo search (CS) algorithm for the sidelobe suppressions of antenna arrays, an improved CS with reverse learning and invasive weed operators (ICSRLIWO) is proposed. First, ICSRLIWO algorithm generates reverse populations through opposition‐based learning method, then selects better individuals in the mixed population consists of the original and reversed population to form a high‐quality initial population. Second, ICSRLIWO introduces the reproducing, space diffusion and survival competition operators of invasive weed optimization to improve the population diversity and global search ability of conventional CS algorithm. Simulations are conducted based on 30 test functions in the CEC 2014 test suit to verify the performance of the proposed approach, and the results show that ICSRLIWO has higher solution accuracy and faster convergence speed than other comparison algorithms. In addition, ICSRLIWO also has advantages in solving the array antenna beam pattern optimization problems.
Motivations and segmentation of the demand for coastal cities: A study in Lima, Peru
Authors: Carvache‐Franco Mauricio , Carvache‐Franco Orly , Carvache‐Franco Wilmer , Alvarez‐Risco Aldo , Estrada‐Merino Alfredo
Published: November 2020

The purpose of this research is to identify the motivations and segmentation of demand in coastal cities. The present study was carried out in Lima, a tourist destination in the Peruvian Pacific Ocean coast. This quantitative study used a sample with 381 valid questionnaires. To analyze data, factor analysis and non‐hierarchical K‐means segmentation were performed. Results show six motivational factors: “Culture and nature,” “Authentic coastal experience,” “Novelty and social interaction,” “Learning,” “Sun and beach,” and “Nightlife.” The study presents three different segments of visitors: “Passive Tourists,” “Eco‐coastal,” and “Multiple motives.”
A Review of Otolaryngology Malpractice Cases with Associated Court Proceedings from 2010 to 2019
Authors: Ceremsak John , Miller Lauren E. , Gomez Ernest D.
Published: November 2020

Objectives/Hypothesis

To report key characteristics of the landscape of malpractice litigation with associated court proceedings in otolaryngology over the previous decade.

Study Design

Retrospective database review.

Methods

The LexisNexis database was queried to identify otolaryngology‐related malpractices cases that yielded court opinions, jury verdicts, and settlements from federal and state courts across the United States from 2010 to 2019. Cases settled outside of court were not identifiable. Provider subspecialty, procedures, error type, legal allegations, and case outcomes were recorded. Frequency of error type was compared between otolaryngology subspecialties using Fisher exact tests.

Results

Ninety‐four medical malpractice cases related to otolaryngology with evidence of court proceedings were identified for the period between 2010 and 2019. An otolaryngologist was named as the sole defendant in 39 cases (41%). Rhinology was the most frequently implicated subspecialty (28% of all cases), followed by head and neck surgery (17%) and facial plastics (7%). Improper surgical performance was cited in nearly half of the identified cases (49%), followed by failure to diagnose/refer/treat (32%). Outcome and liability data were available for 56 cases (60%). Of these 56 cases, 50 (89%) were ruled in favor of the defendant otolaryngologist. Of the cases ruled in favor of the plaintiff, the average indemnity was $4.24 M (range, $150,000 M–$10.25 M). Fisher exact tests demonstrated statistically significant differences in consent issues (P = .040), failure to diagnose/refer/treat (P = .024), and improper surgical performance (P = .026) between subspecialties.

Conclusions

In a limited, database‐derived sample of medical malpractice cases involving otolaryngologists, trends in error type by subspecialty may warrant further investigation to identify specialty‐wide and subspecialty‐specific areas of practice improvement and education.

Level of Evidence

N/A Laryngoscope, 131:E1081–E1085, 2021
Post‐Tonsillectomy Hemorrhage and the Diagnosis of Occult Pediatric Coagulopathies
Authors: Chorney Stephen R. , Weinberger Rena , Weintraub Ari Y. , Buzi Adva
Published: November 2020

Objectives/Hypothesis

The primary objective of this investigation was to determine rates of abnormal coagulation panels and diagnoses of coagulopathies in children with post‐tonsillectomy hemorrhage (PTH). Secondary objectives identified patient demographics and hemorrhage event characteristics that correlated with a coagulopathy diagnosis.

Study Design

Case series with chart review.

Methods

Patients requiring operative control of PTH at a tertiary children's hospital between 2015 and 2019 were included. Details of tonsillectomy procedures and hemorrhage events were reviewed along with screening labs for coagulopathy, referrals to hematology and bleeding disorder diagnoses.

Results

There were 250 children included. Mean age was 8.8 years (95% CI: 8.2–9.4) and 53.6% were males. PTH events occurred at a median of postoperative day six (mean: 5.9, 95% CI: 5.4–6.3), and 14.8% occurred within 24 hours of surgery. In this series, 23 patients (9.2%) had a second PTH, and three (1.2%) had a third PTH. Single and multiple PTH patients were similar with respect to age, gender, postoperative day, and technique (P > .05). Screening coagulation panels were obtained on presentation in 67.8% of children with one PTH and abnormally elevated in 38.3%. All children with multiple PTHs had labs drawn with 34.8% having elevated levels. No child with a single PTH was diagnosed with a bleeding disorder. Conversely, 87.0% of children with multiple PTHs saw hematology and three (13.0%) were diagnosed with a bleeding disorder (P < .001).

Conclusions

Obtaining coagulation panels in pediatric patients presenting with PTH is rarely useful and diagnosing a coagulopathy is uncommon. However, among children with a second PTH, referral to hematology is reasonable as this group has a significantly higher, albeit small, incidence of undiagnosed bleeding disorders.

Level of Evidence

4 Laryngoscope, 131:E2069–E2073, 2021
The prognostic significance of human papilloma virus in sinonasal squamous cell carcinoma
Authors: Schlussel Markovic Emily , Marqueen Kathryn E. , Sindhu Kunal K. , Lehrer Eric J. , Liu Jerry , Miles Brett , Genden Eric , Sharma Sonam , Gupta Vishal , Westra William , Iloreta Alfred , Posner Marshall , Misiukiewicz Krzysztof , Bakst Richard L.
Published: November 2020

Background

Human papilloma virus (HPV) has been implicated in the pathology of oropharyngeal head and neck cancers, but its role in sinonasal squamous cell carcinoma (SNSCC) has not been well established.

Methods

Thirty‐two patients with SNSCC diagnosed between 2011 and 2018 were identified and stratified by HPV status and viral serotype, as determined by PCR. Endpoints including recurrence, metastases and survival were analyzed using the Kaplan‐Meier method.

Results

Seventeen (53%) patients were HPV‐positive and 15 (47%) were HPV‐negative. The median follow‐up time of living patients was 30.7 months (range 4‐123 months). Survival did not differ by HPV status, but HPV+ tumors were more likely to locally recur and metastasize. When stratifying by treatment type, the lowest rate of recurrence occurred in patients receiving surgery and chemoradiation.

Conclusion

A significant proportion of sinonasal tumors appear to be associated with HPV. Testing for HPV might be justified in all cases of sinonasal cancers. Further investigation is warranted to better understand the role of HPV in SNSCC.
Spatial pricing and product allocation in online retailing
Authors: Xue Mengying , He Long
Published: November 2020

Spatial pricing means a retailer price discriminates its customers based on their geographic locations. In this article, we study how an online retailer should jointly allocate multiple products and facilitate spatial price discrimination to maximize profits. When deciding between a centralized product allocation ((i.e., different products are allocated to the same fulfillment center) and decentralized product allocation (ie, different products are allocated to different fulfillment centers), the retailer faces the tradeoff between shipment pooling (ie, shipping multiple products in one package), and demand localization (ie, stocking products to satisfy local demand) based on its understanding of customers' product valuations. In our basic model, we consider two widely used spatial pricing policies: free on board (FOB) pricing that charges each customer the exact amount of shipping cost, and uniform delivered (UD) pricing that provides free shipping. We propose a stylized model and find that centralized product allocation is preferred when demand localization effect is relatively low or shipment pooling benefit is relatively high under both spatial pricing policies. Moreover, centralized product allocation is more preferred under the FOB pricing which encourages the purchase of virtual bundles of multiple products. Furthermore, we respectively extend the UD and FOB pricing policies to flat rate shipping (ie, the firm charges a constant shipping fee for each purchase), and linear rate shipping (ie, the firm sets the shipping fee as a fixed proportion of firm's actual fulfillment costs). While similar observations from the basic model still hold, we find the firm can improve its profit by sharing the fulfillment cost with its customers via the flat rate or linear rate shipping fee structure.
Reliability and structural validity of the Norwegian version of the TeamSTEPPS Teamwork Attitudes Questionnaire: A cross‐sectional study among Bachelor of Nursing students
Authors: Karlsen Tore , Hall‐Lord Marie Louise , Wangensteen Sigrid , Ballangrud Randi
Published: November 2020

Aim

To test the reliability and structural validity of the Norwegian version of the TeamSTEPPS® Teamwork Attitudes Questionnaire (T‐TAQ) among Bachelor of Nursing students.

Design

Cross‐sectional study.

Methods

Bachelor of Nursing students (N = 1,624) at three campuses in different regions of Norway were invited to complete the survey. The data were analysed with descriptive statistics, Cronbach's alpha and confirmatory factor analysis (CFA). Three models were tested. Model 3 was a post hoc modification with a correlation between four negatively worded items. The data was collected in September 2018 and May‐June 2019.

Results

A total of 509 students were included in the study. Cronbach's alpha ranged from 0.44–0.70 for the dimensions and was 0.79 for the total questionnaire. The fit indexes of model 3 were as follows: RMSEA = 0.043, chi‐square = 724.3 (p < .000), normed chi‐square = 1.862, TLI = 0.812 and CFI = 0.832. The questionnaire shows some potential to display attitudes towards teamwork in health care among Bachelor of Nursing students. Low Cronbach's alpha in the dimensions might indicate that the questionnaire should be considered used as a unidimensional questionnaire.
A high order numerical scheme for solving a class of non‐homogeneous time‐fractional reaction diffusion equation
Authors: Roul Pradip , Goura V. M. K. Prasad
Published: November 2020

This paper is concerned with the development of a high order numerical technique for solving time‐fractional reaction–diffusion equation. The fractional derivative in the governing equation is described in the Caputo sense and a collocation method based on quintic B‐spline basis function is used to discretize the space variable. The stability and convergence analysis of the method are investigated, and it is shown that the proposed method converges to the exact solution of the problem with order of convergence O(Δt2 − α + Δx4), where α is the order of fractional derivative (0 < α < 1). Three test problems are considered to illustrate the efficiency and accuracy of present numerical scheme and to verify the theoretical result. It is shown that the order of fractional derivative has a profound effect on the solution of time‐fractional reaction–diffusion equation.
Radial basis solutions of second‐order quasi‐linear hyperbolic boundary value problem
Authors: Soradi‐Zeid Samaneh , Mesrizadeh Mehdi , Cattani Carlo
Published: November 2020

In this study, a new applicable design is studied for solving a second‐order quasi‐linear hyperbolic equation with nonlocal mixed boundary conditions. A localized collocation radial basis functions method is used for spatial discretization. Also, the Taylor method and group preserving scheme are applied for time discretization. Several non‐trivial examples are carried out to evaluate the performance and effectiveness of the suggested framework.
Navigating Diagnostic and Treatment Decisions in Non-Small Cell Lung Cancer: Expert Commentary on the Multidisciplinary Team Approach
Authors: Popat Sanjay , Navani Neal , Kerr Keith M. , Smit Egbert F. , Batchelor Timothy J.P. , Van Schil Paul , Senan Suresh , McDonald Fiona
Published: November 2020

Non-small cell lung cancer (NSCLC) accounts for approximately one in five cancer-related deaths, and management requires increasingly complex decision making by health care professionals. Many centers have therefore adopted a multidisciplinary approach to patient care, using the expertise of various specialists to provide the best evidence-based, personalized treatment. However, increasingly complex disease staging, as well as expanded biomarker testing and multimodality management algorithms with novel therapeutics, have driven the need for multifaceted, collaborative decision making to optimally guide the overall treatment process. To keep up with the rapidly evolving treatment landscape, national-level guidelines have been introduced to standardize patient pathways and ensure prompt diagnosis and treatment. Such strategies depend on efficient and effective communication between relevant multidisciplinary team members and have both improved adherence to treatment guidelines and extended patient survival. This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in NSCLC.

Implications for Practice

This review highlights the value of a multidisciplinary approach to the diagnosis and staging of non-small cell lung cancer (NSCLC) and makes practical suggestions as to how multidisciplinary teams (MDTs) can be best deployed at individual stages of the disease to improve patient outcomes and effectively manage common adverse events. The authors discuss how a collaborative approach, appropriately leveraging the diverse expertise of NSCLC MDT members (including specialist radiation and medical oncologists, chest physicians, pathologists, pulmonologists, surgeons, and nursing staff) can continue to ensure optimal per-patient decision making as treatment options become ever more specialized in the era of biomarker-driven therapeutic strategies.
The utility of real‐world evidence for benefit‐risk assessment, communication, and evaluation of pharmaceuticals: Case studies
Authors: Radawski Christine A. , Hammad Tarek A. , Colilla Susan , Coplan Paul , Hornbuckle Kenneth , Freeman Emily , Smith Meredith Y. , Sobel Rachel E. , Bahri Priya , Arias Ariel E. , Bennett Dimitri
Published: November 2020

Purpose

In recent years, novel types of real‐world evidence (RWE) have played a role in various decision‐making processes relating to medicinal products, including regulatory approval, patient access, health technology assessment, safety monitoring, clinical use, and post‐approval lifecycle management. We therefore reviewed the potential utility of RWE in the cycle of medicinal product benefit‐risk (BR) assessment, communication/risk minimization and evaluation (“BRACE”).

Methods

A convenience sample of illustrative studies was drawn from the published literature and examined. Specifically, we examined the purpose for using RWE, the type of RWE used, its novelty and how it might be integrated with other data and activities of the BRACE cycle, and how it contributed to regulatory decision‐making.

Results

Eight studies were selected with each illustrating a different activity in the BRACE cycle ranging from BR assessment in the preapproval setting, post‐approval assessment of safety or effectiveness, communicating BR information to patients and healthcare professionals, and evaluating the effectiveness of risk minimization initiatives to support a positive BR balance.

Conclusions

RWE has an important role in informing regulatory decision‐making regarding the BR management of medicines. With increasing digitalization, facilitating data collection and stakeholder engagement in health, this role is only expected to expand in the future. To reach the full potential of RWE, both regulators and sponsors will need to be familiar with a range of existing and emerging methods for generating and analyzing such evidence appropriately and achieve convergence regarding how different types of RWE can best be used to inform BR management and decision‐making.
Building an active medical product safety surveillance system in Taiwan: Adaptation of the U.S. Sentinel System common data model structure to the National Health Insurance Research Database in Taiwan
Authors: Huang Kelly , Lin Fang‐Ju , Ou Huang‐Tz , Hsu Chien‐Ning , Huang Ling‐Ya , Wang Chi‐Chuan , Toh Sengwee
Published: November 2020

Purpose

Using real‐world data to support regulatory decision has become a global movement. However, a robust platform for active surveillance of medical product safety has not been established in Taiwan.

Methods

Following the common data model structure of the U.S. Food and Drug Administration's Sentinel System, we built the Taiwan Sentinel Data Model (TSDM) using the National Health Insurance Research Database with longitudinal claims data from 23 million individuals, linked death and cause of death data from a national registry, and linked electronic health record data from a delivery system. We examined the conversion of the TSDM using the Sentinel Data Quality Review and Characterization Programs in a sample of sex‐ and age‐stratified cohort of 3 million individuals.

Results

The TSDM fulfilled the requirements of data quality assurance. Only about 6% of sex and 0.0007% of birth year were missing, and <0.001% of date data had illogical values.

Conclusions

The TSDM‐converted database could be a valuable data resource for domestic pharmacovigilance analysis in Taiwan and cross‐country evaluation.
Incorporating patient generated health data into pharmacoepidemiological research
Authors: Bourke Alison , Dixon William G. , Roddam Andrew , Lin Kueiyu Joshua , Hall Gillian C. , Curtis Jeffrey R. , van der Veer Sabine N. , Soriano‐Gabarró Montse , Mills Juliane K. , Major Jacqueline M. , Verstraeten Thomas , Francis Matthew J. , Bartels Dorothee B.
Published: November 2020

Epidemiology and pharmacoepidemiology frequently employ Real‐World Data (RWD) from healthcare teams to inform research. These data sources usually include signs, symptoms, tests, and treatments, but may lack important information such as the patient's diet or adherence or quality of life. By harnessing digital tools a new fount of evidence, Patient (or Citizen/Person) Generated Health Data (PGHD), is becoming more readily available. This review focusses on the advantages and considerations in using PGHD for pharmacoepidemiological research. New and corroborative types of data can be collected directly from patients using digital devices, both passively and actively. Practical issues such as patient engagement, data linking, validation, and analysis are among important considerations in the use of PGHD. In our ever increasingly patient‐centric world, PGHD incorporated into more traditional Real‐Word data sources offers innovative opportunities to expand our understanding of the complex factors involved in health and the safety and effectiveness of disease treatments. Pharmacoepidemiologists have a unique role in realizing the potential of PGHD by ensuring that robust methodology, governance, and analytical techniques underpin its use to generate meaningful research results.
Effects of monomer composition on physical properties and enzymatic hydrolyzability of poly(butylene succinate‐co‐hexamethylene succinate)s
Authors: Jing Jing , Song Li , Su Tingting , Wang Zhanyong
Published: November 2020

In this study, various biodegradable materials, including poly(butylene succinate) (PBS), poly(hexamethylene succinate) (PHS), and poly(butylene succinate‐co‐hexamethylene succinate)s (P[BS‐co‐HS]s) containing different hexamethylene succinate (HS) contents, were prepared. The compositions, thermal properties, mechanical properties, hydrophilicity, and enzymatic hydrolyzability of the materials were investigated by various techniques. The results showed that the composition of the copolyesters was similar to the feeding ratio of the reactants. The melting and crystallization temperatures, thermal stability, and degree of crystallinity of the copolyesters decreased for low HS content and increased for high HS content. P(BS‐co‐HS)s containing 52 mol% HS exhibited low crystallization temperature (Tc), melting temperature (Tm), degree of crystallinity (Xc), and high hydrophilicity, elongation at break and enzymatic hydrolyzability. We also observed that low degree of crystallinity and high crystal defects, hydrophilicity, and high elongation at break could improve the enzymatic hydrolyzability of the materials.
Two ABC transporters are differentially involved in the toxicity of two Bacillus thuringiensis Cry1 toxins to the invasive crop‐pest Spodoptera frugiperda (J. E. Smith)
Authors: Jin Minghui , Yang Yanchao , Shan Yinxue , Chakrabarty Swapan , Cheng Ying , Soberón Mario , Bravo Alejandra , Liu Kaiyu , Wu Kongming , Xiao Yutao
Published: November 2020

BACKGROUND

The fall armyworm Spodoptera frugiperda is a major agricultural pest that has invaded the East Hemisphere since 2016, generating a serious threat to food security worldwide including Africa and Asia. The Cry toxins produced by Bacillus thuringiensis (Bt) have been shown to be effective against this insect pest. In different insect ABC transporters (ABCC2 or ABCC3) have been shown to be involved as receptors of some Cry1 toxins. Here we analyzed the role of SfABCC2 and SfABCC3 in the toxicity of Cry1Fa and Cry1Ab toxins in this insect pest.

RESULTS

Two S. frugiperda SfABCC2 and SfABCC3 knockout strains, coding for potential functional Bt receptors, were created using CRISPR/Cas9 genome editing system. Both knockout strains showed resistance to both Cry1Fa and Cry1Ab toxins compared with the susceptible strain. SfABCC2 knockout strain showed higher resistance to both Cry toxins than SfABCC3 knockout strain, suggesting a major role of SfABCC2 in the mode of action of these Cry toxins. In addition, expression of SfABCC2 and SfABCC3 genes in Trichoplusia ni Hi5 cells also increased the susceptibility to Cry1Ab and Cry1Fa toxins, in agreement with the genome editing results. The double knockout of SfABCC2 and SfABCC3 strain was not viable in contrast to other lepidopteran species. Furthermore, we report here that SfABCC2 or SfABCC3 knockout strains increased their susceptibility to abamectin and spinosad insecticides.

CONCLUSION

We provide functional evidence that in S. frugiperda these two ABCC transporters serve as receptors of Bt Cry1Fa and Cry1Ab toxins. © 2020 Society of Chemical Industry
On the Littlewood‐Offord problem for arbitrary distributions
Authors: Juškevičius Tomas , Kurauskas Valentas
Published: November 2020

Let X1, … , Xn be independent identically distributed discrete random vectors in . We consider upper bounds on under various restrictions on Xi and weights ai. When , this corresponds to the classical Littlewood‐Offord problem. We prove that in general for identically distributed random vectors and even values of n the optimal choice for (ai) is ai = 1 for and ai = −1 for , regardless of the distribution of X1. Applying these results to Bernoulli random variables answers a recent question of Fox et al. Finally, we provide sharp bounds for concentration probabilities of sums of random vectors under the condition , where it turns out that the worst case scenario is provided by distributions on an arithmetic progression that are in some sense as close to the uniform distribution as possible. Unlike much of the literature on the subject we use neither methods of harmonic analysis nor those from extremal combinatorics.
Efficient semiparametric inference for two‐phase studies with outcome and covariate measurement errors
Authors: Tao Ran , Lotspeich Sarah C. , Amorim Gustavo , Shaw Pamela A. , Shepherd Bryan E.
Published: November 2020

In modern observational studies using electronic health records or other routinely collected data, both the outcome and covariates of interest can be error‐prone and their errors often correlated. A cost‐effective solution is the two‐phase design, under which the error‐prone outcome and covariates are observed for all subjects during the first phase and that information is used to select a validation subsample for accurate measurements of these variables in the second phase. Previous research on two‐phase measurement error problems largely focused on scenarios where there are errors in covariates only or the validation sample is a simple random sample of study subjects. Herein, we propose a semiparametric approach to general two‐phase measurement error problems with a quantitative outcome, allowing for correlated errors in the outcome and covariates and arbitrary second‐phase selection. We devise a computationally efficient and numerically stable expectation‐maximization algorithm to maximize the nonparametric likelihood function. The resulting estimators possess desired statistical properties. We demonstrate the superiority of the proposed methods over existing approaches through extensive simulation studies, and we illustrate their use in an observational HIV study.
Model hierarchy for the shape optimization of a microchannel cooling system
Authors: Blauth Sebastian , Leithäuser Christian , Pinnau René
Published: November 2020

We model a microchannel cooling system and consider the optimization of its shape by means of shape calculus. A three‐dimensional model covering all relevant physical effects and three reduced models are introduced. The latter are derived via a homogenization of the geometry in 3D and a transformation of the three‐dimensional models to two dimensions. A shape optimization problem based on the tracking of heat absorption by the cooler and the uniform distribution of the flow through the microchannels is formulated and adapted to all models. We present the corresponding shape derivatives and adjoint systems, which we derived with a material derivative free adjoint approach. To demonstrate the feasibility of the reduced models, the optimization problems are solved numerically with a gradient descent method. A comparison of the results shows that the reduced models perform similarly to the original one while using significantly less computational resources.
Stability analysis of multiple solutions in case of a stretched nanofluid flow obeying Corcione's correlation: An extended Darcy model
Authors: Kumar Rakesh , Sharma Tanya , Kumar Ravinder , Sheikholeslami Mohsen , Vajravelu Kuppalapalle
Published: November 2020

The bi‐dimensional flow of a ‐water nanofluid perfusing a porous medium has been considered for investigation. The porous space is in contact with a constantly heated sheet stretching at a linear rate. To simulate the nanofluid flow through the pores, an extended Darcy model due to Brinkman and Forchheimer is utilized considering porosity and permeability effects in a convective environment. Corcione's model for effective dynamic viscosity of the nanoparticle mixture is exploited to deduce the effects of nanoparticle size on the flow. Multiple solutions to governing equations are obtained by availing the optimal homotopy asymptotic scheme and discussed for emerging parameters. A unique stable solution is determined availing a stability analysis approach. The heat movement rate is found to be increasing with the reduced nanoparticle size and the enhanced porosity of porous space.
Soft photon theorems from CFT Ward identites in the flat limit of AdS/CFT
Authors: Hijano Eliot , Neuenfeld Dominik
Published: November 2020

Abstract

S-matrix elements in flat space can be obtained from a large AdS-radius limit of certain CFT correlators. We present a method for constructing CFT operators which create incoming and outgoing scattering states in flat space. This is done by taking the flat limit of bulk operator reconstruction techniques. Using this method, we obtain explicit expressions for incoming and outgoing U(1) gauge fields. Weinberg soft photon theorems then follow from Ward identites of conserved CFT currents. In four bulk dimensions, gauge fields on AdS can be quantized with standard and alternative boundary conditions. Changing the quantization scheme corresponds to the S-transformation of SL(2, ℤ) electric-magnetic duality in the bulk. This allows us to derive both, the electric and magnetic soft photon theorems in flat space from CFT physics.
Virasoro blocks and quasimodular forms
Authors: Das Diptarka , Datta Shouvik , Raman Madhusudhan
Published: November 2020

Abstract

We analyse Virasoro blocks in the regime of heavy intermediate exchange (hp→ ∞). For the 1-point block on the torus and the 4-point block on the sphere, we show that each order in the large-hp expansion can be written in closed form as polynomials in the Eisenstein series. The appearance of this structure is explained using the fusion kernel and, more markedly, by invoking the modular anomaly equations via the 2d/4d correspondence. The existence of these constraints allows us to develop a faster algorithm to recursively construct the blocks in this regime. We then apply our results to find corrections to averaged heavy-heavy-light OPE coefficients.
Der Doppelsuizid – Teil 1: juristische Aspekte und historische/zeitgeschichtliche Fälle
Authors: Deschins J. , Holz F. , Duttge G. , Verhoff M. A. , Parzeller M.
Published: November 2020

Bei Suizidformen mit mehreren Suizidenten und Opfern werden teilweise in Literatur und Rechtsprechung eine unterschiedliche Nomenklatur und Interpretation der Begrifflichkeiten vorgenommen. Der Beitrag analysiert die Begrifflichkeiten und befasst sich im Speziellen mit dem Phänomen des Doppelsuizids. Historische Fälle von Doppelsuiziden werden angeführt. Anhand von Fallkonstellationen werden rechtliche Bewertungen vorgenommen, die beim einseitig fehlgeschlagenen Doppelsuizid praxisrelevant werden können. Dabei werden die mitunter konträren Auffassungen in der einschlägigen Literatur und der Rechtsprechung dargestellt und Lösungsansätze aufgezeigt. Zudem verdeutlichen die Fallkonstellationen die Relevanz einer umfassenden Tatortarbeit und einer tatnahen Klärung der Motivationslage bei dem Überlebenden bzw. den Verstorbenen.
An evaluation of a virtual atlas of portion sizes (VAPS) mobile augmented reality for portion size estimation
Authors: Lam Meng Chun , Suwadi Nur Afyfah , Mohd Zainul Arifien Adibah Huda , Poh Bee Koon , Safii Nik Shanita , Wong Jyh Eiin
Published: November 2020

Food portion size estimation is a critical yet challenging task in dietary assessment. Augmented reality technology enables the presentation of food dimensions and volume in a virtual three-dimensional object. It has the potential to improve perception and estimation of portion sizes. This study aims to develop and evaluate a novel mobile augmented reality application, namely Virtual Atlas of Portion Sizes (VAPS), as a portion size estimation aid. The development methodology of VAPS involves food photography, reconstruction of 3D models using photogrammetry method and presenting them in an AR environment. The 3D food models displayed in either semi-transparent or vivid mode for users to perform food portion estimation. Users can then resize and rotate the 3D models to fit the virtual model with the actual food. A total of thirty-six participants were involved in the evaluation and were divided into a health science and a non-health science background group. VAPS received good usability level with 76 SUS score. In terms of task completion time, unsurprisingly, the health science group performed faster. However, both groups have equivalent accuracy on the food portion estimation task using VAPS: 22.5% for non-health science group and 26.6% for health science group. The health science group liked and have better accuracy in vivid 3D food models (37.5%). Meanwhile, the non-health science group preferred semi-transparent 3D food models, but the accuracy is not significantly different between semi-transparent (25%) and vivid 3D food model (20%). Results demonstrate the potential of VAPS to aid in portion size estimation for dietary assessment, and participants’ feedback will be incorporated in the future for improvement of the app.
Quantifying the Backlog of Total Hip and Knee Arthroplasty Cases: Predicting the Impact of COVID-19
Authors: Wilson Jacob M. , Schwartz Andrew M. , Farley Kevin X. , Roberson James R. , Bradbury Thomas L. , Guild George N.
Published: November 2020

Background

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are two high-volume procedures that were delayed due to COVID-19.

Questions/Purposes

To help strategize an effective return to elective orthopedic surgery, we aimed to quantify the volume of THA and TKA cases delayed across the USA and estimate the time required to care for these patients when non-urgent surgery resumes.

Methods

Population-level data was used to estimate monthly THA and TKA procedural volume from 2011 to 2017. Using linear regression, we used this data to project monthly procedural volumes for 2020 to 2023. Nine different permutations were modeled to account for variations in case delay rates (50%, 75%, 100%) and in resumption of non-urgent procedure timing. Two recovery pathways using the highest volume month as a surrogate for maximum operative capacity, and a second using the highest month + 20% were used to simulate a theoretical expansion of current capacity.

Results

The projected national volume of delayed cases was 155,293 (mid-March through April; 95% CI 142,004 to 168,580), 260,806 (through May; 95% CI 238,658 to 282,952), and 372,706 (through June; 95% CI 341,699 to 403,709). The best- and worst-case scenarios for delayed cases were 77,646 (95% CI 71,002 to 84,290) and 372,706 (95% CI 341,699 to 403,709), respectively. The projected catch-up time varied between 9 and nearly 35 months for the best- and worst-case scenarios. The addition of 20% increased productivity decreased this time to between 3.21 and 11.59 months.

Conclusion

The COVID-19 pandemic has generated a significant backlog of THA and TKA procedures. Surgeons, administrators, and policymakers should account for these modeled estimates of case volume delays and projected demands.
Transformation of Surface Roughness of Mg Alloy Tubes During Laser Dieless Drawing
Authors: Milenin Andrij , Furushima Tsuyoshi , Němeček Jiří
Published: November 2020

The paper investigates the transformation of surface roughness of tubes made from magnesium and magnesium alloys as a function of their longitudinal strain during laser dieless drawing. Experimental studies on three materials (AZ31, MgCa08, and pure Mg) have shown that the dependence of roughness on the longitudinal strain is nonlinear and exhibits a minimum. The proposed explanation for this is that the transformation of surface roughness occurs following two mechanisms. The first mechanism involves stretching of the tube and the decreasing of existing roughness with the increasing elongation. The second mechanism is based on the strain-induced surface roughening phenomenon. This mechanism leads to an increase in roughness with the increasing elongation. To analyze these mechanisms, a numerical model of roughness formation is used. It is experimentally shown that the position of the minimum roughness concerning the tube longitudinal strain is correlated with the stress-strain curve of the material under laser dieless drawing conditions. The obtained results provide a practical way to reduce surface roughness of tubes produced by the laser dieless drawing process. According to the proposed method, to achieve minimum roughness, it is necessary to keep the longitudinal strain under a specific value. This value is close to the strain, which corresponds to the maximum stress on the stress-strain curve of the material for temperature and strain rate, corresponding laser dieless drawing conditions.
Hydrocarbon generation from Carboniferous-Permian coaly source rocks in the Huanghua depression under different geological processes
Authors: Xu Jin-Jun , Jin Qiang
Published: November 2020

Natural gas and condensate derived from Carboniferous-Permian (C-P) coaly source rocks discovered in the Dagang Oilfield in the Bohai Bay Basin (east China) have important implications for the potential exploration of C-P coaly source rocks. This study analyzed the secondary, tertiary, and dynamic characteristics of hydrocarbon generation in order to predict the hydrocarbon potentials of different exploration areas in the Dagang Oilfield. The results indicated that C-P oil and gas were generated from coaly source rocks by secondary or tertiary hydrocarbon generation and characterized by notably different hydrocarbon products and generation dynamics. Secondary hydrocarbon generation was completed when the maturity reached vitrinite reflectance (Ro) of 0.7%–0.9% before uplift prior to the Eocene. Tertiary hydrocarbon generation from the source rocks was limited in deep buried sags in the Oligocene, where the products consisted of light oil and gas. The activation energies for secondary and tertiary hydrocarbon generation were 260–280 kJ/mol and 300–330 kJ/mol, respectively, indicating that each instance of hydrocarbon generation required higher temperature or deeper burial than the previous instance. Locations with secondary or tertiary hydrocarbon generation from C-P coaly source rocks were interpreted as potential oil and gas exploration regions.
Subtle Oculomotor Difficulties and Their Relation to Motor Skill in Children with Autism Spectrum Disorder
Authors: Sumner Emma , Hutton Samuel B. , Hill Elisabeth L.
Published: November 2020

Objectives

Sensorimotor difficulties are often reported in autism spectrum disorders (ASD). Visual and motor skills are linked in that the processing of visual information can help in guiding motor movements. The present study investigated oculomotor skill and its relation to general motor skill in ASD by providing a comprehensive assessment of oculomotor control.

Methods

Fifty children (25 ASD; 25 typically developing [TD]), aged 7–10 years, completed a motor assessment (comprising fine and gross motor tasks) and oculomotor battery (comprising fixation, smooth pursuit, prosaccade and antisaccade tasks).

Results

No group differences were found for antisaccade errors, nor saccade latencies in prosaccade and antisaccade tasks, but increased saccade amplitude variability was observed in children with ASD, suggesting a reduced consistency in saccade accuracy. Children with ASD also demonstrated poorer fixation stability than their peers and spent less time in pursuit of a moving target. Motor skill was not correlated with saccade amplitude variability. However, regression analyses revealed that motor skill (and not diagnosis) accounted for variance in fixation performance and fast smooth pursuit.

Conclusions

The findings highlight the importance of considering oculomotor paradigms to inform the functional impact of neuropathologies in ASD and also assessing the presentation of co-occurring difficulties to further our understanding of ASD. Avenues for future research are suggested.