bluuebunny/crossref_metadata_2025 huggingface dataset:
Curves on K3 surfaces in divisibility 2
Authors: Bae Younghan , Buelles Tim-Henrik
Published: February 2021

We prove a conjecture of Maulik, Pandharipande and Thomas expressing the Gromov–Witten invariants of K3 surfaces for divisibility 2 curve classes in all genera in terms of weakly holomorphic quasi-modular forms of level 2. Then we establish the holomorphic anomaly equation in divisibility 2 in all genera. Our approach involves a refined boundary induction, relying on the top tautological group of the moduli space of smooth curves, together with a degeneration formula for the reduced virtual fundamental class with imprimitive curve classes. We use double ramification relations with target variety as a new tool to prove the initial condition. The relationship between the holomorphic anomaly equation for higher divisibility and the conjectural multiple cover formula of Oberdieck and Pandharipande is discussed in detail and illustrated with several examples.
Quality of inpatient antimicrobial use in hematology and oncology patients
Authors: Douglas Abby P. , Hall Lisa , James Rodney S. , Worth Leon J. , Slavin Monica A. , Thursky Karin A.
Published: February 2021

Objectives:

To compare antimicrobial prescribing practices in Australian hematology and oncology patients to noncancer acute inpatients and to identify targets for stewardship interventions.

Design:

Retrospective comparative analysis of a national prospectively collected database.

Methods:

Using data from the 2014–2018 annual Australian point-prevalence surveys of antimicrobial prescribing in hospitalized patients (ie, Hospital National Antimicrobial Prescribing Survey called Hospital NAPS), the most frequently used antimicrobials, their appropriateness, and guideline concordance were compared among hematology/bone marrow transplant (hemBMT), oncology, and noncancer inpatients in the setting of treatment of neutropenic fever and antibacterial and antifungal prophylaxis.

Results:

In 454 facilities, 94,226 antibiotic prescriptions for 62,607 adult inpatients (2,230 hemBMT, 1,824 oncology, and 58,553 noncancer) were analyzed. Appropriateness was high for neutropenic fever management across groups (83.4%–90.4%); however, hemBMT patients had high rates of carbapenem use (111 of 746 prescriptions, 14.9%), and 20.2% of these prescriptions were deemed inappropriate. Logistic regression demonstrated that hemBMT patients were more likely to receive appropriate antifungal prophylaxis compared to oncology and noncancer patients (adjusted OR, 5.3;P< .001 for hemBMT compared to noncancer patients). Oncology had a low rate of antifungal prophylaxis guideline compliance (67.2%), and incorrect dosage and frequency were key factors. Compared to oncology patients, hemBMT patients were more likely to receive appropriate nonsurgical antibacterial prophylaxis (aOR, 8.4; 95% CI, 5.3–13.3;P< .001). HemBMT patients were also more likely to receive appropriate nonsurgical antibacterial prophylaxis compared to noncancer patients (OR, 3.1; 95% CI, 1.9–5.0;P< .001). However, in the Australian context, the hemBMT group had higher than expected use of fluoroquinolone prophylaxis (66 of 831 prescriptions, 8%).

Conclusions:

This study demonstrates why separate analysis of hemBMT and oncology populations is necessary to identify specific opportunities for quality improvement in each patient group.
Association between a rapid diagnostic test to detect methicillin-resistant Staphylococcus Aureus pneumonia and decreased vancomycin use in a medical intensive care unit over a 30-month period
Authors: Pickens Chiagozie I. , Qi Chao , Postelnick Michael , Paonessa Joseph , Donnelly Helen K. , Wunderink Richard G.
Published: February 2021

Vancomycin overuse is common, yet few data are available regarding how to improve stewardship of this antibiotic. We identify an association between use of a PCR assay to rule out MRSA pneumonia and a significant, sustained decrease in average vancomycin days of therapy over a 30-month period.
Pressure propagation and flow restart in the multi-plug gelled pipeline
Authors: Tikariha Lomesh , Kumar Lalit
Published: February 2021

An understanding of pressure propagation mechanisms is crucial in finding suitable conditions for the temporary storage, transmission and attenuation of a large pressure signal in a multi-plug gelled pipeline. The current work investigates the transient flow start in a multi-plug gelled pipeline, filled with a weakly compressible, thixotropic waxy gelled crude oil. A multi-plug gel can form either naturally or artificially. We solve time-dependent mass and momentum conservation equations for the gas phase and conservation equations together with a shear-history-dependent constitutive model for the gel phase to capture the transient phenomena. An advection equation traces the motion of the gel–gas interface using the volume of fluid method. The results of this work show that pressure propagation in the first gel plug compresses it. The compressed first gel plug further compresses the gas pocket, which delays pressure propagation in the downstream gel. The delay in the pressure propagation through the second gel plug creates a high-pressure gradient in the first gel plug. A high-pressure gradient in the first gel results in faster degradation of the first gel. Degraded gel offers a substantially lower resistance to flow, allowing a high-pressure gradient in the second gel. A steeper pressure gradient assists the breakage of the next gel plug and results in a sequential gel breakage. This sequential gel breakage allows flow restart in a long pipeline. The results also indicate that the compressibility of the gas pocket dominates the overall compressibility of the system, controlling both pressure propagation and flow-restart time.
Distributive/integrative negotiation strategies in cross-cultural contexts: a comparative study of the USA and Italy
Authors: Benetti Sara , Ogliastri Enrique , Caputo Andrea
Published: February 2021

Integrative and distributive negotiation strategies are a key paradigm of practice, teaching, and research. Are these US-formulated negotiation prototypes valid in the rest of the world? Adopting a cross-cultural view, we analyze a sample of 214 foreigners who detailed the negotiation behavior they faced in Italy (134) and in the United States (80). Implementing latent class analysis, we identify three clusters of negotiation prototypes. Our findings show how the Country is a predictor for cluster membership, and peculiar cultural traits of the two groups contribute to explain the differences in negotiation strategies. Three prototypes emerged: a typically distributive, an emotional integrative (mostly Italian), and an impersonal integrative (mostly American). Results show how the handling of emotions is a crucial part of the interaction for Italian negotiators, regardless of their orientation toward negotiation strategies, implying a cultural influence toward handling emotions in negotiations.
Uncommon preservation of dinosaur footprints in a tidal breccia:Eubrontes giganteusfrom the Early Jurassic Mongisty tracksite of Aveyron, southern France
Authors: Moreau Jean-David , Sciau Jacques , Gand Georges , Fara Emmanuel
Published: February 2021

A recent excavation yielded 118 large tridactyl footprints in the Lower Jurassic Dolomitic Formation of the Causses Basin, at Mongisty in southern France. Most of the tracks are ascribed toEubrontes giganteusHitchcock, 1845. They are preserved on a surface of 53 m2and form parallel rows with a preferential orientation towards the north. Such an abundance and density ofE. giganteusis observed for the first time in the Early Jurassic from the Causses Basin. Sedimentological and ichnotaphonomical analyses show that the footprints were made at different time intervals, thus excluding the passage of a large group. In contrast to all other tracksites from the Dolomitic Formation, where tracks are preserved in fine-grained sediments corresponding to low-energy depositional palaeoenvironments, the tracks from Mongisty are preserved in coarse-grained sediment which is a matrix- to clast-supported breccia. Clasts consist of angular to sub-rounded, millimetric to centimetric-scale (up to 2 cm), poorly sorted, randomly oriented, homogeneous dolostone intraclasts floating in a dolomudstone matrix. Sedimentological analysis shows that the depositional environments of Mongisty varied from subtidal to intertidal/supratidal settings in a large and protected flat marsh. The lithology of the track-bearing surfaces indicates that the mudflat of the Causses Basin was sporadically affected by large mud flows that reworked and redeposited mudstone intraclasts coming from the erosion of upstream, dry and partially lithified mud beds. Throughout the world, this type of preservation of dinosaur tracks in tidal matrix- to clast-supported breccias remains rare.
Using a 4K three-dimensional exoscope system (Vitom 3D) for mastoid surgery during the coronavirus disease 2019 pandemic
Authors: Ally M , Kullar P , Mochloulis G , Vijendren A
Published: February 2021

Objective

Microscopic surgery is currently considered the ‘gold standard’ for middle-ear, mastoid and lateral skull base surgery. The coronavirus disease 2019 pandemic has made microscopic surgery more challenging to perform. This work aimed to demonstrate the feasibility of the Vitom 3D system, which integrates a high-definition (4K) view and three-dimensional technology for ear surgery, within the context of the pandemic.

Method

Combined approach tympanoplasty and ossiculoplasty were performed for cholesteatoma using the Vitom 3D system exclusively.

Results

Surgery was performed successfully. The patient made a good recovery, with no evidence of residual disease at follow up. The compact system has excellent depth of field, magnification and colour. It enables ergonomic work, improved work flow, and is ideal for teaching and training.

Conclusion

The Vitom 3D system is considered a revolutionary alternative to microscope-assisted surgery, particularly in light of coronavirus disease 2019. It allows delivery of safe otological surgery, which may aid in continuing elective surgery.
Cooperation, fairness and team reasoning
Authors: Duijf Hein
Published: February 2021

This paper examines two strands of literature regarding economic models of cooperation. First, payoff transformation theories assume that people may not be exclusively motivated by self-interest, but also care about equality and fairness. Second, team reasoning theorists assume that people might reason from the perspective of the team, rather than an individualistic perspective. Can these two theories be unified? In contrast to the consensus among team reasoning theorists, I argue that team reasoning can be viewed as a particular type of payoff transformation. However, I also demonstrate that many payoff transformations yield actions that team reasoning rules out.
The joint development of externalizing and internalizing behaviors in black and Hispanic youth and the link to late adolescent substance use
Authors: Bears Augustyn Megan , Fulco Celia J. , Agbeke Della , Henry Kimberly L.
Published: February 2021

There is a need to understand how the joint development of externalizing and internalizing behaviors is related to substance use, particularly among historically understudied and often disadvantaged populations. Latent class models were used to estimate patterns of externalizing behaviors and internalizing behaviors in the form of depressive and anxious symptoms from age 6 to 14 among 390 Black and Hispanic youth. Then, growth curve models of substance use between the ages of 15 and 19 were estimated as a function of joint latent class membership. Only elevated levels of externalizing behaviors were associated with higher levels of substance use through age 18. Internalizing behaviors appeared to serve as a protective factor among those with moderate displays of externalizing behavior only. Additionally, growth in substance use from ages 15 to 19 was slower among those who displayed the highest level of externalizing behaviors, and internalizing behaviors appeared to moderate growth (and serve as protective factor) among those who displayed moderate levels of externalizing behaviors. The findings underscore the importance of pattern profiles based on observations of the joint development of problem behaviors to assess risk for substance use, particularly in understudied populations where risk/protective factors may operate in a unique manner.
How matrix metalloproteinase (MMP)-9 (rs3918242) polymorphism affects MMP-9 serum concentration and associates with autism spectrum disorders: A case-control study in Iranian population
Authors: Lord Javid Rezaei , Mashayekhi Farhad , Salehi Zivar
Published: February 2021

The aim of this project was to evaluate the relationship of matrix metalloproteinase-9 (MMP-9) genetic variation and its serum concentration with autism spectrum disorder (ASD). One hundred ASD and 120 controls were enrolled in this study. Genomic DNA was extracted from blood and MMP-9 polymorphism was determined by polymerase chain reaction restriction fragment length polymorphism and serum levels were measured by enzyme-linked immunosorbent assay. The frequencies of CC, CT, and TT genotypes were 72%, 26%, and 2% in controls and 31%, 57%, and 12% in ASD, respectively. The frequencies of C and T alleles in ASD were 59.5% and 40.5%, and controls were 86% and 14%, respectively. There is a significant increase in serum MMP-9 levels in ASD as compared to controls. We have also shown that TT genotype is significantly associated with increase serum MMP-9 levels in patients (TT, CT, and CC serum levels were 91.77 ± 10.53, 70.66 ± 7.21, and 38.66 ± 5.52 and in controls were 55.55 ± 11.39, 42.66 ± 7.85, and 30.55 ± 6.34 ng/ml, respectively). It is concluded that there is a significant association between rs3918242 MMP-9 polymorphism and its serum concentration with autism. We also suggest that TT genotype is associated with increased MMP9 expression and may be a risk factor for ASD.
On the Erdős–Sós conjecture for trees with bounded degree
Authors: Besomi Guido , Pavez-Signé Matías , Stein Maya
Published: February 2021

We prove the Erdős–Sós conjecture for trees with bounded maximum degree and large dense host graphs. As a corollary, we obtain an upper bound on the multicolour Ramsey number of large trees whose maximum degree is bounded by a constant.
Treatment of attention deficit/hyperactivity disorder in children with CHD
Authors: Pierick Alyson R. , Lynn Melodie , McCracken Courtney M. , Oster Matthew E. , Iannucci Glen J.
Published: February 2021

Introduction:

The prevalence of attention deficit/hyperactivity disorder in the general population is common and is now diagnosed in 4%–12% of children. Children with CHD have been shown to be at increased risk for attention deficit/hyperactivity disorder. Case reports have led to concern regarding the use of attention deficit/hyperactivity disorder medications in children with underlying CHD. We hypothesised that medical therapy for patients with CHD and attention deficit/hyperactivity disorder is safe.

Methods:

A single-centre, retrospective chart review was performed evaluating for adverse events in patients aged 4–21 years with CHD who received attention deficit/hyperactivity disorder therapy over a 5-year span. Inclusion criteria were a diagnosis of CHD and concomitant medical therapy with amphetamines, methylphenidate, or atomoxetine. Patients with trivial or spontaneously resolved CHD were excluded from analysis.

Results:

In 831 patients with CHD who received stimulants with a mean age of 12.9 years, there was only one adverse cardiovascular event identified. Using sensitivity analysis, our median follow-up time was 686 days and a prevalence rate of 0.21% of adverse events. This episode consisted of increased frequency of supraventricular tachycardia in a patient who had this condition prior to initiation of medical therapy; the condition improved with discontinuation of attention deficit/hyperactivity disorder therapy.

Conclusion:

The incidence of significant adverse cardiovascular events in our population was similar to the prevalence of supraventricular tachycardia in the general population. Our single-centre experience demonstrated no increased risk in adverse events related to medical therapy for children with attention deficit/hyperactivity disorder and underlying CHD. Further population-based studies are indicated to validate these findings.
Improving the Appropriateness of Advanced Life Support Teams’ Dispatch: A Before-After Study
Authors: Gamberini Lorenzo , Picoco Cosimo , Del Giudice Donatella , Zenesini Corrado , Tartaglione Marco , Coniglio Carlo , Semeraro Federico , Bizzi Fabrizio , Santini Stefano , Gordini Giovanni
Published: February 2021

Background and Importance:

The dispatch of Advanced Life Support (ALS) teams in Emergency Medical Services (EMS) is still a hardly studied aspect of prehospital emergency logistics. In 2015, the dispatch algorithm of Emilia Est Emergency Operation Centre (EE-EOC) was implemented and the dispatch of ALS teams was changed from primary to secondary based on triage of dispatched vehicles for high-priority interventions when teams with Immediate Life Support (ILS) skills were dispatched.

Objectives:

This study aimed to evaluate the effects on the appropriateness of ALS teams’ intervention and their employment time, and to compare sensitivity and specificity of the algorithm implementation.

Design:

This was a retrospective before-after observational study.

Settings and Participants:

Primary dispatches managed by EE-EOC involving ambulances and/or ALS teams were included. Two groups were created on the basis of the years of intervention (2013-2014 versus 2017-2018).

Intervention:

A switch from primary to secondary dispatch of ALS teams in case of high-priority dispatches managed by ILS teams was implemented.

Outcomes:

Appropriateness of ALS team intervention, total task time of ALS vehicles, and sensitivity and specificity of the algorithm were reviewed.

Results:

The study included 242,501 emergency calls that generated 56,567 red code dispatches. The new algorithm significantly increased global sensitivity and specificity of the system in terms of recognition of potential need of ALS intervention and the specificity of primary ALS dispatch. The appropriateness of ALS intervention was significantly increased; total tasking time per day for ALS and the number of critical dispatches without ALS available were reduced.

Conclusion:

The revision of the dispatch criteria and the extension of the two-tiered dispatch for ALS teams significantly increased the appropriateness of ALS intervention and reduced both the global tasking time and the number of high-priority dispatches without ALS teams available.
Hemodialysis Clinics in Flood Zones: A Case Study of Hurricane Harvey
Authors: Kaiser Rebecca , Karaye Ibraheem M. , Olokunlade Temitope , Hammond Tracy Anne , Goldberg Daniel W. , Horney Jennifer A.
Published: February 2021

Introduction:

Hurricane Harvey (2017) forced the closure of hemodialysis centers across Harris County, Texas (USA) disrupting the provision of dialysis services. This study aims to estimate the percentage of hemodialysis clinics flooded after Harvey, to identify the proportion of such clinics located in high-risk flood zones, and to assess the sensitivity of the Federal Emergency Management Agency (FEMA) Flood Insurance Rate Maps (FIRMs) for estimation of flood risk.

Methods:

Data on 124 hemodialysis clinics in Harris County were extracted fromMedicare.govand geocoded using ArcGIS Online. The FIRMs were overlaid to identify the flood zone designation of each hemodialysis clinic.

Results:

Twenty-one percent (26 of 124) of hemodialysis clinics in Harris County flooded after Harvey. Of the flooded clinics, 57.7% were in a high-risk flood zone, 30.8% were within 1km of a high-risk flood zone, and 11.5% were not in or near a high-risk flood zone. The FIRMs had a sensitivity of 58%, misidentifying 42% (11 of 26) of the clinics flooded.

Conclusion:

Hurricanes are associated with severe disruptions of medical services, including hemodialysis. With one-quarter of Harris County in the 100-year floodplain, projected increases in the frequency and severity of disasters, and inadequate updates of flood zone designation maps, the implementation of new regulations that address the development of hemodialysis facilities in high-risk flood areas should be considered.
A machine translation mechanism of Brazilian Portuguese to Libras with syntactic-semantic adequacy
Authors: Lima Manuella Aschoff C. B. , de Araújo Tiago Maritan U. , Costa Rostand E. O. , Oliveira Erickson S.
Published: February 2021

Deaf people communicate naturally using visual-spatial languages, called sign languages (SL). Although SLs are recognized as a language in many countries, the problems faced by Deaf people for accessing information remain. As a result, they have difficulties exercising their citizenship and access information in SLs, which usually leads to linguistic and knowledge acquisition delays. Some scientific works have been developed to address these problems related to the machine translation of spoken languages to sign languages. However, the existing machine translation platforms have some limitations, especially in syntactic and lexical nature. Thus, this work aims to develop a mechanism for machine translation to Libras, the Brazilian Sign Language, with syntactic-semantic adequacy. It consists of an automatic translation component for Libras based on syntactic-semantic translation rules and a formal syntactic-semantic rule description language. As proof of concept of the proposed approach, we created a specific grammar for Libras translation exploring these aspects and integrating these elements into VLibras Suite, a service for machine translation of digital content in Brazilian Portuguese (BP) to Libras. We performed several tests using this modified version of VLibras to measure the level of comprehension of the output generated by the new translator mechanism. In the computational experiments, as well as in the actual tests with Deaf and hearing users, the proposed approach was able to improve the results of the current VLibras version.
Disentangling food insecurity and maternal depression: which comes first?
Authors: Reesor-Oyer Layton , Cepni Aliye B , Lee Che Young , Zhao Xue , Hernandez Daphne C
Published: February 2021

Objective:

To determine the temporal directionality of the association between food insecurity and maternal depression.

Design:

Food insecurity was measured at two time points using the eighteen-item USDA Food Security Scale. Maternal depression was measured at two time points using the fifteen-item Composite International Diagnostic Interview-Short Form. Two structural equation models were utilised to evaluate the impact of food insecurity on maternal depression (model 1) and the impact of maternal depression on food insecurity (model 2). Both models controlled for socio-demographic and parenting characteristics and child behaviour problems, along with prior measures of the dependent variable and concurrent measures of the independent variable.

Setting:

Fragile Families and Child Wellbeing (FFCW) study, twenty cities across the USA.

Participants:

4897 mothers who participated in two waves of the FFCW study.

Results:

On average, 17 % (time 1) and 15 % (time 2) of mothers experienced food insecurity and 21 % (time 1) and 17 % (time 2) of mothers experienced depression over time. Maternal depression at time 1 was associated with 53 % increased odds (OR = 1·53; B = 0·43;P< 0·001) of food insecurity at time 2, controlling for time 1 food insecurity, concurrent depression and covariates. Food insecurity at time 1 was associated with 36 % increased odds (OR = 1·36; B = 0·31;P< 0·001) of maternal depression at time 2, controlling for time 1 depression, concurrent food insecurity and covariates.

Conclusions:

We found a bidirectional relationship between food insecurity and maternal depression. A holistic approach that combines food assistance and mental health services may be an efficacious approach to reducing both depressive symptoms and food insecurity among low-income mothers.
Development and testing of the Sustainable Nutrition Environment Measures Survey for retail stores in Ontario
Authors: Mollaei Sadaf , Dias Goretty M , Minaker Leia M
Published: February 2021

Objective:

To develop and test a tool to assess the price and availability of low-carbon footprint and nutritionally balanced dietary patterns in retail food environments in Ontario, Canada.

Design:

Availability and price of selected food from discount and regular grocery stores (n 23) in urban/rural areas of northern/southern Ontario were assessed with the Sustainable Nutrition Environment Measures Survey in 2017.

Setting:

Ontario, Canada.

Results:

Inter-rater reliability was high for price (intra-class correlation coefficients = 0·819) and for availability (Cohen’s κ = 0·993). The tool showed 78 % of the selected food items were available in all stores. Overall, price differences were small between urban and rural locations, and northern and southern Ontario. The greatest price difference was between discount and regular stores.

Conclusions:

The tool showed excellent inter-rater agreement. Researchers and public health dietitians can use this tool for research, practice and policy to link consumer-level health outcomes to the retail environment.
Targets missed: three case studies exploiting the linked SHARE-RV data
Authors: Börsch-Supan Axel , Bucher-Koenen Tabea , Goll Nicolas , Hanemann Felizia
Published: February 2021

Targeting is an important aim of social policy. Three case studies in this paper reflect typical short-comings in the targeting design of pension reforms. The first case study examines how well work disability and receipt of disability insurance match in Germany. We show that the 2001 reform has not systematically improved target quality. The second case study examines whether the 2014 introduction of a new pathway of early retirement without actuarial adjustments has reached individuals who are less healthy because they have worked a long time in an arduous job. We find that the target population is actually healthier than the comparison group. Third, a much discussed supplemental pension benefit for households in the risk of poverty will miss its target population in both relevant directions: Regarding the first, 23% of those pensioners who are not eligible are nevertheless poor in the sense of the new law. Regarding the other direction, 21% of the eligible pensioners belong to the wealthier half of German pensioners. Since similar reforms are currently debated in many European countries, the three German case studies may serve as examples of how to better target public pension policies.
THEBODY, THESTRANGER, ANDCORDON MINORITAIRE
Authors: Asey Farid
Published: February 2021

Canada is touted as a diverse, tolerant, and multicultural country where the prevailing understanding is that racial injustices emanating from structural oppression are not widespread. Analysing lived experiences of racialized participants who worked in publicly funded places of employment in British Columbia (BC), this qualitative study offers a phenomenological exploration of a particular manifestation of racial discrimination: that of quarantine-like containment of mobility at work. Examining undue restrictions and mobility limitations imposed on participants, this article will use three metaphors—strangerfor racialized individuals,bodyfor workplaces, andcordon minoritaireas the process of containing the mobility of strangers within the body—to present and discuss findings on: 1) excessive targeted scrutiny; 2) wrongful seating arrangements; 3) cold and transactional interactions; and, 4) bad faith references. In this regard,cordon minoritaireis presented as a novel analytical framework to illustrate the ways in which racialized workers were cordoned off, with their professional freedoms and career mobilities restricted, in order to quarantine White ecosystems of employment. Consequently,cordon minoritairemachinations created perniciously unequal conditions that fundamentally and unjustly constrained participants into working under discriminatory conditions—depravities that are at odds with whimsical notions of Canada as tolerant, multicultural, and morally superior to its neighbour south of the border.
“RECONSTRUCTION HAS STOPPED THE NONSENSE”
Authors: Price-Spratlen Townsand , Guzman Joseph , Patton Charles , Goldsby William
Published: February 2021

Increasing research attention is being given to former felons, or returning citizens, after their release from prison. This paper contributes to that dialogue by exploring the documentary-making process of a grassroots organization founded by and for returning citizens and their families, and the contributions it made when it was completed in 1996, and continues to make today. Little is known about how community organizations can use the making of an organizational documentary to build the capacities of the organization, its affiliates, a neighborhood, and social change. By exploring the collaborations and challenges that took place during the local reintegration process back into family and community, the start and completion of the documentary in the mid-1990s was quite innovative. This article analyzes reciprocal tensions of service (Simmel 1908) reflected in the documentary when it was completed in 1996, and its continuing relevance to the growth of returning citizenship today.
Why we need to face up to the ageing population?
Authors: Dixon Anna
Published: February 2021

Dr Anna Dixon, Chief Executive at the Centre for Ageing Better, examines the issues around an ageing population, how we have reached this stage and offers potential solutions to the problems it presents. Her book, The Age of Ageing Better? turns the misleading and depressing narrative of burden and massive extra cost of people living longer on its head and shows how our society could thrive if we started thinking differently. She presents a refreshingly optimistic vision for the future that could change the way we value later life in every sense.
Physician behaviour, malpractice risk and defensive medicine: an investigation of cesarean deliveries
Authors: Mushinski David , Zahran Sammy , Frazier Aanston
Published: February 2021

Analyzing whether physicians use cesarean sections (c-sections) as defensive medicine (DM) has proven difficult. Using natural experiments arising out of Oregon court decisions overturning a state legislative cap on non-economic damages in tort cases, we analyze the impact of patient conditions on estimates of DM. Consistent with theory, we find heterogeneous impacts of tort laws across patient conditions. When medical exigencies dictate a c-section, tort laws have no impact on physician decisions. When physicians have latitude in their decision making, we find evidence of DM. When we estimate a model combining all women and not accounting for patient conditions (such as models estimated in previous studies) we obtain a result which is the opposite of DM, which we call offensive medicine (OM). The OM result appears to arise out of a bias in the difference-in-differences estimator associated with changes in the marginal distributions of patient conditions in control and treatment groups. The changes in the marginal distributions appear to arise from the impact of tort law on the market for midwives (substitutes for physicians for low-risk women). Our analysis suggests that not accounting for theoretically expected heterogeneity in physician reactions to changes in tort laws may produce biased estimates of DM.
Modulation of αVβ6 integrin in osteoarthritis-related synovitis and the interaction with VTN(381–397 a.a.) competing for TGF-β1 activation
Authors: Ciregia Federica , Deroyer Céline , Cobraiville Gaël , Plener Zelda , Malaise Olivier , Gillet Philippe , Fillet Marianne , Malaise Michel G. , de Seny Dominique
Published: February 2021

Osteoarthritis is characterized by structural alteration of joints. Fibrosis of the synovial tissue is often detected and considered one of the main causes of joint stiffness and pain. In our earlier proteomic study, increased levels of vitronectin (VTN) fragment (amino acids 381–397) were observed in the serum of osteoarthritis patients. In this work, the affinity of this fragment for integrins and its putative role in TGF-β1 activation were investigated. A competition study determined the interaction of VTN(381–397 a.a.) with αVβ6 integrin. Subsequently, the presence of αVβ6 integrin was substantiated on primary human fibroblast-like synoviocytes (FLSs) by western blot and flow cytometry. By immunohistochemistry, β6 was detected in synovial membranes, and its expression showed a correlation with tissue fibrosis. Moreover, β6 expression was increased under TGF-β1 stimulation; hence, a TGF-β bioassay was applied. We observed that αVβ6 could mediate TGF-β1 bioavailability and that VTN(381–397 a.a.) could prevent TGF-β1 activation by interacting with αVβ6 in human FLSs and increased α-SMA. Finally, we analyzed serum samples from healthy controls and patients with osteoarthritis and other rheumatic diseases by nano-LC/Chip MS–MS, confirming the increased expression of VTN(381–397 a.a.) in osteoarthritis as well as in lupus erythematosus and systemic sclerosis. These findings corroborate our previous observations concerning the overexpression of VTN(381–397 a.a.) in osteoarthritis but also in other rheumatic diseases. This fragment interacts with αVβ6 integrin, a receptor whose expression is increased in FLSs from the osteoarthritic synovial membrane and that can mediate the activation of the TGF-β1 precursor in human FLSs.
Extending the resolution limits of nanoshape imprint lithography using molecular dynamics of polymer crosslinking
Authors: Cherala Anshuman , Pandya Parth N. , Liechti Kenneth M. , Sreenivasan S. V.
Published: February 2021

Emerging nanoscale applications in energy, electronics, optics, and medicine can exhibit enhanced performance by incorporating nanoshaped structures (nanoshape structures here are defined as shapes enabled by sharp corners with radius of curvature < 5 nm). Nanoshaped fabrication at high-throughput is well beyond the capabilities of advanced optical lithography. Although the highest-resolution e-beams and large-area e-beams have a resolution limit of 5 and 18 nm half-pitch lines or 20 nm half-pitch holes, respectively, their low throughput necessitates finding other fabrication techniques. By using nanoimprint lithography followed by metal-assisted chemical etching, diamond-like nanoshapes with ~3 nm radius corners and 100 nm half-pitch over large areas have been previously demonstrated to improve the nanowire capacitor performance (by ~90%). In future dynamic random-access memory (DRAM) nodes (with DRAM being an exemplar CMOS application), the implementation of nanowire capacitors scaled to <15 nm half-pitch is required. To scale nanoshape imprint lithography down to these half-pitch values, the previously established atomistic simulation framework indicates that the current imprint resist materials are unable to retain the nanoshape structures needed for DRAM capacitors. In this study, the previous simulation framework is extended to study improved shape retention by varying the resist formulations and by introducing novel bridge structures in nanoshape imprinting. This simulation study has demonstrated viable approaches to sub-10 nm nanoshaped imprinting with good shape retention, which are matched by experimental data.
Correction to: MEMS-actuated metasurface Alvarez lens
Authors: Han Zheyi , Colburn Shane , Majumdar Arka , Böhringer Karl F.
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41378-020-00233-y
Correction to: Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids
Authors: Arzua Thiago , Yan Yasheng , Jiang Congshan , Logan Sarah , Allison Reilly L. , Wells Clive , Kumar Suresh N. , Schäfer Richard , Bai Xiaowen
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41398-021-01214-z.
Desialylation of Atg5 by sialidase (Neu2) enhances autophagosome formation to induce anchorage-dependent cell death in ovarian cancer cells
Authors: Satyavarapu Eswara Murali , Nath Shalini , Mandal Chitra
Published: February 2021

Increased sialylation is one of the hallmarks of ovarian cancer (OC) but its relation with programmed cell death is not known. Here we explored the molecular interplay between autophagy, apoptosis/anoikis, and aberrant-expression of the PI3K-Akt/mTOR pathway in the context of sialidase. OC is accompanied by low expression of cytosolic sialidase (Neu2) and ~10-fold more α2,6- than α2,3-linked sialic acids found through qPCR, western blot, and flow cytometry. Interestingly, Neu2 overexpression cleaved α2,6- and α2,3-linked sialic acids and reduced cell viability. Several autophagy-related molecules like LC3B/Atg3/Atg5/Atg7/Atg12/Atg16L1/Beclin1 were upregulated upon Neu2 overexpression. Atg5, a crucial protein for autophagosome formation, was desialylated by overexpressed Neu2. Desialylated Atg5 now showed enhanced association both with Atg12 and Atg16L1 leading to more autophagosome formation. Neu2-overexpressing cells exhibited extrinsic pathway-mediated apoptosis as reflected the in activation of Fas/FasL/FADD/Bid/caspase 8/caspase 6/caspase 3/PARP cleavage. There was also increased Bax, reduced Bcl2, and several cell-cycle molecules (CDK2/CDK4/CDK6/cyclin-B1/cyclin-E). Inhibition of autophagy using bafilomycin A1 or Beclin1 siRNA leads to reversal of Neu2-induced apoptosis suggesting their possible relationship. Additionally, overexpressed Neu2 inhibited growth factor-mediated signaling molecules involved in the PI3K/Akt-mTOR pathway probably through their desialylation. Furthermore, overexpressed Neu2 inhibited epithelial (ZO-1/Claudin1), mesenchymal (snail/slug), and cell-adhesion (integrin-β3/focal-adhesion kinase) molecules suggesting anchorage-dependent cell death (anoikis). Such changes were absent in the presence of bafilomycin A1 indicating the involvement of autophagy in Neu2-induced anoikis. The physiological relevance of our in vitro observations was further confirmed in the OC xenograft model. Taken together, it is the first report demonstrating that Atg5 is a sialoglycoprotein having α2,6- and α2,3-linked sialic acids and its desialylation by overexpressed Neu2 leads to its activation for autophagosome formation, which induced apoptosis/anoikis in OC.
Preparation and properties of silicone rubber materials with foam/solid alternating multilayered structures
Authors: Zhang Wenhuan , Deng Zhaoping , Yuan Hongwei , Luo Shikai , Wen Huayin , Liu Tao
Published: February 2021

In this paper, silicone rubber materials with foam/solid alternating multilayered structures were successfully constructed by combining the two methods of multilayered hot-pressing and supercritical carbon dioxide (SCCO2) foaming. The cellular morphology and mechanical properties of the foam/solid alternating multilayered silicone rubber materials were systematically studied. The results show that the growth of the cell was restrained by the solid layer, resulting in a decrease in the cell size. In addition, the introduction of the solid layer effectively improved the mechanical properties of the microcellular silicone rubber foam. The tensile strength and compressive strength of the foam/solid alternating multilayered silicone rubber materials reached 5.39 and 1.08 MPa, which are 46.1% and 237.5% of the pure silicone rubber foam, respectively. Finite element analysis (FEA) was applied and the results indicate that the strength and proportion of the solid layer played important roles in the tensile strength of the foam/solid alternating multilayered silicone rubber materials. Moreover, the small cellular structures in silicone rubber foam can provided a high supporting counterforce during compression, meaning that the microcellular structure of silicone rubber foam improved the compressive property compared to that for the large cellular structure of silicone rubber foam.
The H+-pyrophosphatase IbVP1 regulates carbon flux to influence the starch metabolism and yield of sweet potato
Authors: Fan Weijuan , Zhang Yandi , Wu Yinliang , Zhou Wenzhi , Yang Jun , Yuan Ling , Zhang Peng , Wang Hongxia
Published: February 2021

Storage roots of sweet potato are important sink organs for photoassimilates and energy, and carbohydrate metabolism in storage roots affects yield and starch production. Our previous study showed that sweet potato H+-pyrophosphatase (IbVP1) plays a vital role in mitigating iron deficiency and positively controls fibrous root growth. However, its roles in regulating starch production in storage roots have not been investigated. In this study, we found that IbVP1 overexpression in sweet potato improved the photosynthesis ability of and sucrose content in source leaves and increased both the starch content in and total yield of sink tissues. Using 13C-labeled sucrose feeding, we determined that IbVP1 overexpression promotes phloem loading and sucrose long-distance transport and enhances Pi-use efficiency. In sweet potato plants overexpressing IbVP1, the expression levels of starch biosynthesis pathway genes, especially AGPase and GBSSI, were upregulated, leading to changes in the structure, composition, and physicochemical properties of stored starch. Our study shows that the IbVP1 gene plays an important role in regulating starch metabolism in sweet potato. Application of the VP1 gene in genetic engineering of sweet potato cultivars may allow the improvement of starch production and yield under stress or nutrient-limited conditions.
Loci discovery, network-guided approach, and genomic prediction for drought tolerance index in a multi-parent advanced generation intercross (MAGIC) cowpea population
Authors: Ravelombola Waltram , Shi Ainong , Huynh Bao-Lam
Published: February 2021

Cowpea is a nutrient-dense legume that significantly contributes to the population’s diet in sub-Saharan Africa and other regions of the world. Improving cowpea cultivars to be more resilient to abiotic stress such as drought would be of great importance. The use of a multi-parent advanced generation intercross (MAGIC) population has been shown to be efficient in increasing the frequency of rare alleles that could be associated with important agricultural traits. In addition, drought tolerance index has been reported to be a reliable parameter for assessing crop tolerance to water-deficit conditions. Therefore, the objectives of this study were to evaluate the drought tolerance index for plant growth habit, plant maturity, flowering time, 100-seed weight, and grain yield in a MAGIC cowpea population, to conduct genome-wide association study (GWAS) and identify single nucleotide polymorphism (SNP) markers associated with the drought tolerance indices, to investigate the potential relationship existing between the significant loci associated with the drought tolerance indices, and to conduct genomic selection (GS). These analyses were performed using the existing phenotypic and genotypic data published for the MAGIC population which consisted of 305 F8 recombinant inbred lines (RILs) developed at University of California, Riverside. The results indicated that: (1) large variation in drought tolerance indices existed among the cowpea genotypes, (2) a total of 14, 18, 5, 5, and 35 SNPs were associated with plant growth habit change due to drought stress, and drought tolerance indices for maturity, flowering time, 100-seed weight, and grain yield, respectively, (3) the network-guided approach revealed clear interactions between the loci associated with the drought tolerance traits, and (4) the GS accuracy varied from low to moderate. These results could be applied to improve drought tolerance in cowpea through marker-assisted selection (MAS) and genomic selection (GS). To the best of our knowledge, this is the first report on marker loci associated with drought tolerance indices in cowpea.
Identification and analysis of splicing quantitative trait loci across multiple tissues in the human genome
Authors: Garrido-Martín Diego , Borsari Beatrice , Calvo Miquel , Reverter Ferran , Guigó Roderic
Published: February 2021

Alternative splicing (AS) is a fundamental step in eukaryotic mRNA biogenesis. Here, we develop an efficient and reproducible pipeline for the discovery of genetic variants that affect AS (splicing QTLs, sQTLs). We use it to analyze the GTEx dataset, generating a comprehensive catalog of sQTLs in the human genome. Downstream analysis of this catalog provides insight into the mechanisms underlying splicing regulation. We report that a core set of sQTLs is shared across multiple tissues. sQTLs often target the global splicing pattern of genes, rather than individual splicing events. Many also affect the expression of the same or other genes, uncovering regulatory loci that act through different mechanisms. sQTLs tend to be located in post-transcriptionally spliced introns, which would function as hotspots for splicing regulation. While many variants affect splicing patterns by altering the sequence of splice sites, many more modify the binding sites of RNA-binding proteins. Genetic variants affecting splicing can have a stronger phenotypic impact than those affecting gene expression.
Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors
Authors: Valero Cristina , Lee Mark , Hoen Douglas , Weiss Kate , Kelly Daniel W. , Adusumilli Prasad S. , Paik Paul K. , Plitas George , Ladanyi Marc , Postow Michael A. , Ariyan Charlotte E. , Shoushtari Alexander N. , Balachandran Vinod P. , Hakimi A. Ari , Crago Aimee M. , Long Roche Kara C. , Smith J. Joshua , Ganly Ian , Wong Richard J. , Patel Snehal G. , Shah Jatin P. , Lee Nancy Y. , Riaz Nadeem , Wang Jingming , Zehir Ahmet , Berger Michael F. , Chan Timothy A. , Seshan Venkatraman E. , Morris Luc G. T.
Published: February 2021

Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types. Combining NLR with tumor mutational burden (TMB), the probability of benefit from ICI is significantly higher (OR = 3.22; 95% CI, 2.26-4.58; P < 0.001) in the NLR low/TMB high group compared to the NLR high/TMB low group. NLR is a suitable candidate for a cost-effective and widely accessible biomarker, and can be combined with TMB for additional predictive capacity.