bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood obesity prevention across borders: A National Institutes of Health commentary
Authors: Vorkoper Susan , Arteaga S. Sonia , Berrigan David , Bialy Kevin , Bremer Andrew A. , Cotton Paul , Czajkowski Susan , Neilson Elizabeth , Osganian Stavroula K. , Pratt Charlotte A. , Price Le Shawndra N. , Tabor Derrick C. , Walker Jenelle R. , Williams Makeda J. , Anand Nalini
Published: March 2021

In response to the increasing rates of childhood obesity, the United States and countries across Latin America have invested in research that tests innovative strategies and interventions. Despite this, progress has been slow, uneven, and sporadic, calling for increased knowledge exchange and research collaboration that accelerate the adaptation and implementation of promising childhood obesity interventions. To share research results, challenges, and proven intervention strategies among Latin American and US researchers, particularly those working with Latino and Latin American populations, the National Institutes of Health (NIH) convened researchers from the United States and Latin America to highlight synergies between research conducted in Latin America and among Latino populations in the United States with the goal of catalyzing new relationships and identifying common research questions and strategies. This article highlights the NIH's research and priorities in childhood obesity prevention as well as areas for future direction, including overarching NIH plans and NIH institutes, centers, and offices investments in specific areas related to childhood obesity prevention in Latin America and/or among Latino populations in the United States.
Dual function of clock component OsLHY sets critical day length for photoperiodic flowering in rice
Authors: Sun Changhui , Zhang Kuan , Zhou Yi , Xiang Lin , He Changcai , Zhong Chao , Li Ke , Wang Qiuxia , Yang Chuanpeng , Wang Qian , Chen Congping , Chen Dan , Wang Yang , Liu Chuanqiang , Yang Bin , Wu Hualin , Chen Xiaoqiong , Li Weitao , Wang Jing , Xu Peizhou , Wang Pingrong , Fang Jun , Chu Chengcai , Deng Xiaojian
Published: March 2021

Circadian clock, an endogenous time‐setting mechanism, allows plants to adapt to unstable photoperiod conditions and induces flowering with proper timing. In Arabidopsis, the central clock oscillator was formed by a series of interlocked transcriptional feedback loops, but little is known in rice so far. By MutMap technique, we identified the candidate gene OsLHY from a later flowering mutant lem1 and further confirmed it through genetic complementation, RNA interference knockdown, and CRISPR/Cas9‐knockout. Global transcriptome profiling and expression analyses revealed that OsLHY might be a vital circadian rhythm component. Interestingly, oslhy flowered later under ≥12 h day length but headed earlier under ≤11 h day length. qRT‐PCR results exhibited that OsLHY might function through OsGI‐Hd1 pathway. Subsequent one‐hybrid assays in yeast, DNA affinity purification qPCR, and electrophoretic mobility shift assays confirmed OsLHY could directly bind to the CBS element in OsGI promoter. Moreover, the critical day length (CDL) for function reversal of OsLHY in oslhy (11–12 h) was prolonged in the double mutant oslhy osgi (about 13.5 h), indicating that the CDL set by OsLHY was OsGI dependent. Additionally, the dual function of OsLHY entirely relied on Hd1, as the double mutant oslhy hd1 showed the same heading date with hd1 under about 11.5, 13.5, and 14 h day lengths. Together, OsLHY could fine‐tune the CDL by directly regulating OsGI, and Hd1 acts as the final effector of CDL downstream of OsLHY. Our study illustrates a new regulatory mechanism between the circadian clock and photoperiodic flowering.
Treatment of scarring alopecia from trauma and surgical procedures in young patients using follicular unit hair transplantation
Authors: Nuri Takashi , Abe Norihisa , Sakamoto Aritaka , Tsushima Akitoshi , Kasai Yoshiaki , Narui Yuya , Ueda Koichi
Published: March 2021

Introduction

Hair loss due to scarring as a consequence of surgical procedures and trauma can impact young patients socially and emotionally. Recently follicular unit extraction (FUE) hair transplantation has been applied to scar treatment.

Patients and Methods

This report included four patients with scarring alopecia. All patients were female with a mean age of 12.5 years. Previous operations that caused scarring were sebaceous nevus excision with direct closure (n = 2), an extensive burn scar treated using an expander (n = 1) and cauterization for a congenital pigmented nevus (n = 1). The average size of the affected area was 10.5 cm2. The FUE transplantation procedure was performed under local anesthesia. The number of grafts was set at approximately 25‐30 grafts/ cm2 of scar. An electronic punch with a diameter of 0.8 mm was used for graft harvesting, and a 0.6‐mm electronic punch was used to make cylindrical holes on recipient site. The donor sites were shaved followed by graft harvesting in two cases. For the other two cases, harvesting was done without shaving.

Results

The number of transplanted grafts was 60 to 600 (mean 288), and surgical time was 38 to 220 minutes (mean 108). The average dose of lidocaine was 1.4 mg/kg. The average survival rate of the grafts was 85%.

Conclusion

Our experience in these cases suggests that this technique may be a viable option for the treatment of certain causes of scarring alopecia in the pediatric age group.
Acceptance and outcome of interventions in a meropenem de‐escalation antimicrobial stewardship program in pediatrics
Authors: Rungsitsathian Kanokporn , Wacharachaisurapol Noppadol , Nakaranurack Chotirat , Usayaporn Sang , Sakares Watchara , Kawichai Surinda , Jantarabenjakul Watsamon , Puthanakit Thanyawee , Anugulruengkitt Suvaporn
Published: March 2021

Background

Prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with attending physicians to tailor antibiotic therapy, including de‐escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of ASP de‐escalation recommendations in children who received meropenem.

Methods

A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary‐care teaching hospital. The ASP team gave recommendation between 72 and 120 h after initiating meropenem therapy. Acceptance of de‐escalation recommendations among primary physicians was evaluated within 24 h of recommendation. Outcomes included clinical success rate on the 7th day and incidence rate of acquisition of carbapenem‐resistant gram‐negative bacteria (CR‐GNB) within 30 days.

Results

From March to December 2019, 217 children with a median (interquartile range) age of 2.1 (0.6, 9.5) years received meropenem. The ASP team gave recommendations in 127 (58.5%) of cases for continuation of meropenem therapy and 90 (41.5%) of cases for de‐escalation. The overall acceptance of ASP de‐escalation recommendations was 57.8% (95%CI: 46.9–68.1%). Clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (P = 0.06). The incidence rate of acquisition of CR‐GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (P = 0.03).

Conclusions

About half of the recommendations to de‐escalate meropenem prescriptions were accepted through the ASP intervention. Carbapenem‐resistant gram‐negative bacteria acquisitions was less likely in the de‐escalation group. A robust de‐escalation strategy 72 h following carbapenem initiation should be encouraged to combat multidrug‐resistant organisms.
Isolated solar angioedema: A systematic review of the literature
Authors: Aronovich Anna , Snast Igor , Lapidoth Moshe , Leshem Yael A. , Enk Claes D. , Tal Yuval , Mimouni Daniel , Hodak Emmilia , Levi Assi
Published: March 2021

Solar urticaria is a well‐recognized photodermatosis, sometimes accompanied by angioedema. However, isolated solar angioedema (ISA) is a rare and unrecognized entity. The purpose of our work was to systematically review the available data on ISA. Therefore, a systematic review of studies evaluating ISA was performed. Additionally, a case of a 21‐years‐old patient from our photodermatosis service is presented. The search yielded 421 publications, with 3 eligible for review. Together with our case, 5 cases were included overall. All patients were female. Four out of 5 patients first experienced ISA at childhood or early adulthood (age range 6‐22 years). UVA photoprovocation was positive in the 3 out of the 4 patients who were tested. Improvement was noted following NB‐UVB hardening (2 out of 5 patients) or a short course of oral prednisone (3 out of 5 patients) combined with regular sunscreen application. To conclude, ISA is an extremely rare entity, although it may be underdiagnosed due to lack of awareness. The clinician must consider ISA in the differential diagnosis of angioedema since it can have a detrimental effect on quality of life. Besides sun avoidance, there is no consensus regarding treatment.
Severe maternal morbidity at delivery and postpartum readmission in the United States
Authors: Matas Jennifer L. , Mitchell Laura E. , Sharma Shreela V. , Louis Judette M. , Salemi Jason L.
Published: March 2021

Background

Little is known about the extent to which severe maternal morbidity (SMM) at delivery impacts early and late postpartum readmission.

Objectives

We examined readmission rates for women with and without SMM (and their 18 subtypes) at delivery and characterised the most common medical reasons for readmissions.

Methods

We conducted a retrospective cohort study utilising the 2016‐2017 Nationwide Readmissions Database among women giving births in the United States. Deliveries were classified according to the presence or absence of 18 SMM indicators defined by the Centers for Disease Control and Prevention using the International Classification of Diseases, Tenth Edition, Clinical Modification (ICD‐10‐CM) diagnosis and procedure codes. The primary outcome of this study was all‐cause early (≤7 day) and late (8 to 42 day) postpartum readmission. Survey‐weighted Poisson regression with robust error variance was used to generate adjusted risk ratios (RR) and 95% confidence intervals (CI) to investigate the association between SMM and early and late postpartum readmission. Additionally, we compared principal diagnoses codes during readmission hospitalisations among women with and without SMM at delivery.

Results

Of the 6 193 852 women examined, 4.9% (n = 4928) with any SMM and 1.4% (n = 83 995) with no SMM were readmitted within 42 days after delivery. After adjusting for obstetric co‐morbidities and sociodemographic factors, women with any SMM were 57% (RR 1.57, 95% CI 1.47, 1.67) more likely to have an early readmission and 69% (RR 1.69, 95% CI 1.57, 1.82) more likely to have a late readmission compared to women with no SMM at delivery. However, the risk was attenuated when excluding women with blood transfusion only. Women with and without SMM were readmitted predominantly for obstetric complications and infections.

Conclusions

Women with SMM at delivery were more likely to experience both early and late postpartum readmission, independent of their obstetrical co‐morbidity burden and sociodemographic factors.
Innovating and transforming during COVID‐19: insights from Italian firms
Authors: Ferrigno Giulio , Cucino Valentina
Published: March 2021

During the COVID‐19 pandemic, a huge number of firms had to stop their activities due to the lockdown situation that has been decided in most countries. However, to contribute to the many emergencies caused by the pandemic through purpose‐led actions, many of those firms have reacted with innovative projects and changes in their manufacturing activities. In this paper, we address why and how these efforts have been implemented and how the situation of these firms evolved after the peak of the health crisis. Drawing on the literature about the purpose and R&D/innovation management concerning health emergency, we develop a conceptual framework to understand how different types of purpose‐led actions (i.e., short term and/or long term) and different R&D management strategies (i.e., exploitation or exploration of R&D, innovation, and manufacturing competencies) can characterize firms’ rapid response for the benefit of the community in the fight against COVID‐19, for example through the provision of medical equipment or other products and services. We validate the framework using the cases of 21 Italian firms which have taken very fast actions during the peak of the COVID‐19 emergency.
Glycine alleviates fluoride‐induced oxidative stress, apoptosis and senescence in a porcine testicular Sertoli cell line
Authors: Liu Ying , Sun Boxing , Zhang Shaoxuan , Li Jing , Qi Jiajia , Bai Chunyan , Zhang Jiabao , Liang Shuang
Published: March 2021

Contents

Glycine is a well‐known free radical scavenger in the cellular antioxidant system that prevents oxidative damage and apoptosis. Excessive fluoride exposure is associated with multiple types of cellular damage in humans and animals. The objective of the present study was to investigate the protective effects of glycine on sodium fluoride (NaF) exposure and the possible underlying mechanisms in a porcine testicular Sertoli cell line model. Cellular viability and proliferation were examined following NaF exposure and glycine supplementation, and glycine dramatically ameliorated the decreases in NaF‐induced porcine testicular Sertoli cell viability and proliferation. Further investigations revealed that glycine decreased NaF‐induced intracellular reactive oxygen species production, DNA fragment accumulation and the apoptosis incidence in the porcine testicular Sertoli cell line; in addition, glycine improved mitochondrial function and ATP production. Notably, results of the SPiDER‐β‐Gal analysis suggested that glycine alleviated NaF‐induced cellular senescence and downregulated P53, P21, HMGA2 and P16INK4a gene expression in the porcine testicular Sertoli cell line. Collectively, the beneficial effects of glycine alleviate NaF‐induced oxidative stress, apoptosis and senescence, and together with our previous findings, support the hypothesis that glycine plays an important role in protecting against NaF exposure‐induced impairments in the porcine testicular Sertoli cell line.
Adjusted method of penis fixation during boar semi‐automatic semen collection aiming to reduce bacterial contamination
Authors: Paschoal Aline Fernanda Lopes , Mellagi Ana Paula Gonçalves , Ferrari Cristina Vicenti , Takeuti Karine Ludwig , Oliveira Gabriela da Silva , Bernardi Mari Lourdes , Ulguim Rafael da Rosa , Bortolozzo Fernando Pandolfo
Published: March 2021

Semen collection has an essential role in the initial bacterial load in boar ejaculates and extended semen. The study aimed to explore the efficacy of an adjusted penis fixation in a semi‐automatic collection system on reducing bacterial contamination of ejaculates in two‐boar studs with different scenarios. Historically, stud A had low levels of bacterial load in raw semen, while stud B had a high level of contamination. A total of 56 mature boars had their semen collected using two methods of penis fixation: (a) Traditional: The penis was fixed directly with the artificial cervix and transferred to the adjustable clamp; (b) Adjusted: The fixation was performed with one gloved‐hand, and after exteriorization, the penis was gripped using the artificial cervix with the other gloved‐hand and transferred to the adjustable clamp. The bacterial load (p = .0045) and the occurrence of ejaculates >231 CFU/ml (p = .0101) were reduced in the Adjusted compared to the Traditional method. Bacterial load was reduced when using the Adjusted method in stud B (p = .0011), which showed a greater occurrence of critical factors for bacterial contamination (p ≤ .0034). The Adjusted method reduced the occurrence of ejaculates >231 CFU/ml when the preputial ostium was dirty (p = .016) and the duration of semen collection was >7 min (p = .022) compared to the Traditional method. In conclusion, the Adjusted penis fixation was efficient in reducing bacterial load of ejaculates, mainly in boar stud B, which had high contamination challenges.
Irregular perverse sheaves
Authors: Kuwagaki Tatsuki
Published: March 2021

We introduce irregular constructible sheaves, which are ${\mathbb {C}}$-constructible with coefficients in a finite version of the Novikov ring $\Lambda$ and special gradings. We show that the bounded derived category of cohomologically irregular constructible complexes is equivalent to the bounded derived category of holonomic ${\mathcal {D}}$-modules by a modification of D’Agnolo and Kashiwara's irregular Riemann–Hilbert correspondence. The bounded derived category of cohomologically irregular constructible complexes is equipped with the irregular perverse $t$-structure, which is a straightforward generalization of usual perverse $t$-structure, and we prove that its heart is equivalent to the abelian category of holonomic ${\mathcal {D}}$-modules. We also develop the algebraic version of the theory.
Evidence Theory Representations for Properties Associated With Weak Link/Strong Link Systems, Part 2: Failure Time and Failure Temperature
Authors: Helton Jon C. , Brooks Dusty M. , Darby John L.
Published: March 2021

The use of evidence theory and associated cumulative plausibility functions (CPFs), cumulative belief functions (CBFs), cumulative distribution functions (CDFs), complementary cumulative plausibility functions (CCPFs), complementary cumulative belief functions (CCBFs), and complementary cumulative distribution functions (CCDFs) in the analysis of loss of assured safety (LOAS) for weak link (WL)/strong link (SL) systems is introduced and illustrated. Article content includes cumulative and complementary cumulative belief, plausibility, and probability for (i) time at which LOAS occurs for a one WL/two SL system, (ii) time at which a two-link system fails, (iii) temperature at which a two-link system fails, and (iv) temperature at which LOAS occurs for a one WL/two SL system. The presented results can be generalized to systems with more than one WL and two SLs.
Effects of Axial Casing Grooves on the Structure of Turbulence in the Tip Region of an Axial Turbomachine Rotor
Authors: Chen Huang , Li Yuanchao , Koley Subhra Shankha , Katz Joseph
Published: March 2021

Challenges in turbulence modeling in the tip region of turbomachines include anisotropy, inhomogeneity, and non-equilibrium conditions, resulting in poor correlations between Reynolds stresses and the corresponding mean strain-rate components. The geometric complexity introduced by casing grooves exacerbates this problem. Taking advantage of a large database collected in the refractive index-matched liquid facility at Johns Hopkins University (JHU), this paper examines the effect of axial casing grooves on the distributions of turbulent kinetic energy (TKE), Reynolds stresses, anisotropy tensor, and TKE production rate in the tip region of an axial turbomachine. The comparisons are performed at flowrates corresponding to prestall and best efficiency points of the untreated machine. Common features include high TKE near the tip leakage vortex center and in the shear layer connecting it to the blade suction side tip corner. The turbulence is highly anisotropic and inhomogeneous, with the anisotropy tensor shifting from one-dimensional (1D) to 2D and 3D structures over small distances. With the grooves, the flow structure, hence the distribution of Reynolds stresses, becomes more complex. Additional sites with elevated turbulence include the corner vortex that develops at the entrance to the grooves, and in the flow jetting out of the grooves into the passage. Consistent with trends of the production rates of normal Reynolds stress components, the grooves increase the axial but reduce the radial velocity fluctuations as the inflow and outflow from the groove interact with the passage flow. These findings might assist the development of Reynolds stress models suitable for tip flows.
Influence of quantum-confined device fabrication on semiconductor-laser theory
Authors: Chow Weng W. , Jahnke Frank
Published: March 2021

Among Professor Arthur Gossard’s many contributions to crystal growth are those resulting in important improvements in the quality and performance of quantum-well and quantum-dot semiconductor lasers. In celebration of his 85th birthday, we review the development of a semiconductor laser theory that is motivated and guided, in part, by those advances. This theory combines condensed matter theory and laser physics to provide understanding at a microscopic level, i.e., in terms of electrons and holes, and their interaction with the radiation field while influenced by the lattice.
Kinematic Characteristics of the Standing Long Jump in Young Children Aged 4–5 Years
Authors: Ogawa Mana , Ohtaka Chiaki , Fujiwara Motoko , Nakata Hiroki
Published: March 2021

The authors investigated the kinematic characteristics of the standing long jump in preschool children. Sixty 4-year-old children (boys: 30 and girls: 30) and sixty 5-year-old children (boys: 30 and girls: 30) participated in the present study. The authors focused on three differences in kinematics: between 4- and 5-year-old children, between boys and girls, and between high and low jumping performance groups at the same age. The kinematic data included the maximum flexions of the knee and hip before takeoff, at takeoff, and on landing; angular displacement of the upper body; takeoff speeds in horizontal and vertical directions; and takeoff angle of the greater trochanter. Anthropometric variables and kinematic data were separately analyzed with factors of age, sex, and group. The authors also performed multiple regression analysis to identify predictors of the jump distance. The movement speed of the greater trochanter in a horizontal direction, the maximum flexion angle of the hip before takeoff, and the hip angle on landing were identified as significant predictors of the jump distance among young children. These findings suggest that knowing how to use the hip and awareness of the horizontal direction are key factors to improve the long jump distance in young children.
Efficacy of Topical Vancomycin- and Gentamicin-Loaded Calcium Sulfate Beads or Systemic Antibiotics in Eradicating Polymicrobial Biofilms Isolated from Diabetic Foot Infections within an
In Vitro
Wound Model
Authors: Crowther G. S. , Callaghan N. , Bayliss M. , Noel A. , Morley R. , Price B.
Published: March 2021

Diabetic foot ulcers are notoriously difficult to heal, with ulcers often becoming chronic, in many cases leading to amputation despite weeks or months of antibiotic therapy in addition to debridement and offloading. Alternative wound biofilm management options, such as topical rather than systemic delivery of antimicrobials, have been investigated by clinicians in order to improve treatment outcomes.
Efficient Nitrification and Low-Level N
2
O Emission in a Weakly Acidic Bioreactor at Low Dissolved-Oxygen Levels Are Due to Comammox
Authors: Li Deyong , Fang Fang , Liu Guoqiang
Published: March 2021

Nitrification in wastewater treatment is an important process for eutrophication control and an emission source for the greenhouse gas N
2
O. The nitrifying process is usually operated at a slightly alkaline pH and high DO (>2 mg/liter) to ensure efficient nitrification.
Stable Recombinant-Gene Expression from a
Ligilactobacillus
Live Bacterial Vector via Chromosomal Integration
Authors: Vezina Ben , Allnutt Theo , Keyburn Anthony L. , Wade Ben , Van Thi Thu Hao , Johanesen Priscilla , Lyras Dena , Moore Robert J.
Published: March 2021

Therapeutic proteins such as antigens can be used to prevent infectious diseases in poultry. However, traditional vaccine delivery by intramuscular or subcutaneous injection generally has not proven effective for mucosa-dwelling microorganisms that live within the gastrointestinal tract.
Exposure to 1-Butanol Exemplifies the Response of the Thermoacidophilic Archaeon Sulfolobus acidocaldarius to Solvent Stress
Authors: Benninghoff Jens C. , Kuschmierz Laura , Zhou Xiaoxiao , Albersmeier Andreas , Pham Trong Khoa , Busche Tobias , Wright Phillip C. , Kalinowski Jörn , Makarova Kira S. , Bräsen Christopher , Flemming Hans-Curt , Wingender Jost , Siebers Bettina
Published: March 2021

Archaea
are unique in terms of metabolic and cellular processes, as well as the adaptation to extreme environments. In the past few years, the development of genetic systems and biochemical, genetic, and polyomics studies has provided deep insights into the physiology of some archaeal model organisms.
Lymphotoxin β Receptor: a Crucial Role in Innate and Adaptive Immune Responses against Toxoplasma gondii
Authors: Tersteegen Anne , Sorg Ursula R. , Virgen-Slane Richard , Helle Marcel , Petzsch Patrick , Dunay Ildiko R. , Köhrer Karl , Degrandi Daniel , Ware Carl F. , Pfeffer Klaus
Published: March 2021

The lymphotoxin β receptor (LTβR) plays an essential role in the initiation of immune responses to intracellular pathogens. In mice, the LTβR is crucial for surviving acute toxoplasmosis; however, until now, a functional analysis was largely incomplete.
Porcine Hemagglutinating Encephalomyelitis Virus InfectionIn VivoandEx Vivo
Authors: Mora-Díaz Juan Carlos , Piñeyro Pablo E. , Rauh Rolf , Nelson William , Sankoh Zianab , Gregg Edward , Carrillo-Ávila José Antonio , Shen Huigang , Nelli Rahul K. , Zimmerman Jeffrey J. , Giménez-Lirola Luis G.
Published: March 2021

Among the ∼46 virus species in the familyCoronaviridae(2019), many of which are important pathogens of humans and 6 of which are commonly found in pigs, porcine hemagglutinating encephalomyelitis remains one of the least researched. The present study provided a comprehensive characterization of the PHEV infection process and immune responses using CDCD neonatal pigs.
Modeling Unsteady Bénard-Marangoni Instabilities in Drying Volatile Droplets on a Heated Substrate
Authors: Gavrilina A. A. , Barash L. Yu.
Published: March 2021

We study unsteady internal flows in a sessile droplet of capillary size evaporating in constant contact line mode on a heated substrate. Three-dimensional simulations of internal flows in evaporating droplets of ethanol and silicone oil have been carried out. For describing the Marangoni flows we find it necessary to account for the diffusion of vapor in air, the thermal conduction in all three phases and thermal radiation. The equations have been solved numerically by finite element method using ANSYS Fluent. As a result of the simulations, the nonstationary behavior of Bénard-Marangoni (BM) instabilities is obtained. At the first stage, a flower structure of BM cells near the triple line emerge. For smaller contact angles, the cells grow in size and occupy the central region of the droplet surface. Being closely connected with recent experimental and theoretical studies, the results obtained help to analyze and resolve the associated issues.
Time trends in the incidence of clinically diagnosed type 2 diabetes and pre-diabetes in the UK 2009–2018: a retrospective cohort study
Authors: Pal Kingshuk , Horsfall Laura , Sharma Manuj , Nazareth Irwin , Petersen Irene
Published: March 2021

Introduction

To describe recent trends in the incidence of clinically diagnosed type 2 diabetes and pre-diabetes in people seen in UK general practice.

Research design and methods

A retrospective cohort study using IQVIA Medical Research Data looking at people newly diagnosed with type 2 diabetes and pre-diabetes through primary care registers in the UK between 1 January 2009 and 31 December 2018.

Results

A cohort of 426 717 people were clinically diagnosed with type 2 diabetes and 418 656 people met the criteria for a diagnosis of pre-diabetes in that time period. The incidence of clinically diagnosed type 2 diabetes per 1000 person years at risk (PYAR) in men decreased from a peak of 5.06 per 1000 PYAR (95% CI 4.97 to 5.15) in 2013 to 3.56 per 1000 PYAR (95% CI 3.46 to 3.66) by 2018. For women, the incidence of clinically diagnosed type 2 diabetes per 1000 PYAR decreased from 4.45 (95% CI 4.37 to 4.54) in 2013 to 2.85 (2.76 to 2.93) in 2018. The incidence rate of pre-diabetes tripled by the end of the same study period in men and women.

Conclusions

Between 2009 and 2018, the incidence rate of new clinical diagnoses of type 2 diabetes recorded in a UK primary care database decreased by a third from its peak in 2013–2014, while the incidence of pre-diabetes has tripled. The implications of this on timely treatment, complication rates and mortality need further longer term exploration.
Multimorbidity, ageing and mortality: normative data and cohort study in an American population
Authors: Rocca Walter A , Grossardt Brandon R , Boyd Cynthia M , Chamberlain Alanna M , Bobo William V , St Sauver Jennifer L
Published: March 2021

Objectives

To describe the percentile distribution of multimorbidity across age by sex, race and ethnicity, and to demonstrate the utility of multimorbidity percentiles to predict mortality.

Design

Population-based descriptive study and cohort study.

Setting

Olmsted County, Minnesota (USA).

Participants

We used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years).

Methods

For each person, we obtained the count of chronic conditions (out of 20 conditions) present on each birthday by extracting all of the diagnostic codes received in the 5 years before the index birthday from the electronic indexes of the REP. To compare each person’s count to peers of same age, the counts were transformed into percentiles of the total population and displayed graphically across age by sex, race and ethnicity. In addition, quintiles 1, 2, 4 and 5 were compared with quintile 3 (reference) to predict the risk of death at 1 year, 5 years and through end of follow-up using time-to-event analyses. Follow-up was passive using the REP.

Results

We identified 238 010 persons who experienced a total of 1 458 094 birthdays during the study period (median of 6 birthdays per person; IQR 3–10). The percentiles of multimorbidity across age did not vary noticeably by sex, race or ethnicity. In general, there was an increased risk of mortality at 1 and 5 years for quintiles 4 and 5 of multimorbidity. The risk of mortality for quintile 5 was greater for younger age groups and for women.

Conclusions

The assignment of multimorbidity percentiles to persons in a population may be a simple and intuitive tool to assess relative health status, and to predict short-term mortality, especially in younger persons and in women.
Technical capacities needed to implement the WHO’s primary eye care package for Africa: results of a Delphi process
Authors: Aghaji Ada , Burchett Helen E D , Mathenge Wanjiku , Faal Hannah Bassey , Umeh Rich , Ezepue Felix , Isiyaku Sunday , Kyari Fatima , Wiafe Boateng , Foster Allen , Gilbert Clare E
Published: March 2021

Objective

The aim of the study was to establish the technical capacities needed to deliver the WHO African Region’s primary eye care package in primary healthcare facilities.

Design

A two-round Delphi exercise was used to obtain expert consensus on the technical complexity of each component of the package and the technical capacities needed to deliver them using Gericke’s framework of technical feasibility. The panel comprised nine eyecare experts in primary eyecare in sub-Saharan Africa. In each round panel members used a 4-point Likert scale to indicate their level of agreement. Consensus was predefined as ≥70% agreement on each statement. For round 1, statements on technical complexity were identified through a literature search of primary eyecare in sub-Saharan Africa from January 1980 to April 2018. Statements for which consensus was achieved were included in round 2, and the technical capacities were agreed.

Results

Technical complexity statements were classified into four broad categories: intervention characteristics, delivery characteristics, government capacity requirements and usage characteristics. 34 of the 38 (89%) statements on health promotion and 40 of the 43 (93%) statements on facility case management were considered necessary technical capacities for implementation.

Conclusion

This study establishes the technical capacities needed to implement the WHO Africa Office primary eye care package, which may be generalisable to countries in sub-Saharan Africa.
Navigating choice in the face of uncertainty: using a theory informed qualitative approach to identifying potential patient barriers and enablers to participating in an early phase chimeric antigen receptor T (CAR-T) cell therapy trial
Authors: Castillo Gisell , Lalu Manoj M , Asad Sarah , Foster Madison , Kekre Natasha , Fergusson Dean A , Hawrysh Terry , Atkins Harold , Thavorn Kednapa , Montroy Joshua , Schwartz Stuart , Holt Robert A , Broady Raewyn , Presseau Justin
Published: March 2021

Objectives

Bench to bedside translation of groundbreaking treatments like chimeric antigen receptor T (CAR-T) cell therapy depends on patient participation in early phase trials. Unfortunately, many novel therapies fail to be adequately evaluated due to low recruitment rates, which slows patient access to emerging treatments. Using the Theoretical Domains Framework (TDF), we sought to identify potential patient barriers and enablers to participating in an early phase CAR-T cell therapy trial.

Design

We used qualitative semistructured interviews to identify potential barriers and enablers to patients’ hypothetical participation in an early phase CAR-T cell therapy trial. We used the TDF and directed content analysis to identify relevant domains based on frequency, relevance and the presence of conflicting beliefs.

Participants

Canadian adult patients diagnosed with haematological malignancies.

Results

In total, we interviewed 13 participants (8 women, 5 men). Participants ranged in age from 18 to 73 (median=56) and had been living with haematological cancer from a few months to several years. We found participants were unfamiliar with CAR-T cell therapy but wished to know more about treatment safety, efficacy and trial logistics (domains: knowledge, beliefs about consequences). They were motivated by altruistic considerations, though many prioritised personal health benefits despite recognising the goals (ie, establishing safety) of early phase clinical trials (domains: goals, intentions). Every participant valued receiving medical advice from their haematologists and oncologists, though some preferred impartial medical experts to inform their decision making (domain: social influences). Finally, participants indicated that improving access to financial and social supports would improve their trial participation experience (domain: environmental context and resources).

Conclusion

Using the TDF allowed us to identify factors that might undermine participation to a CAR-T cell therapy trial and to optimise recruitment processes by considering patient perspectives to taking part in early phase trials.

Trial regestration:NCT03765177; Pre-results.
CBLBablation with CRISPR/Cas9 enhances cytotoxicity of human placental stem cell-derived NK cells for cancer immunotherapy
Authors: Guo Xuan , Mahlakõiv Tanel , Ye Qian , Somanchi Srinivas , He Shuyang , Rana Hemlata , DiFiglia Andrea , Gleason Joseph , van der Touw William , Hariri Robert , Zhang Xiaokui
Published: March 2021

Background

Tumors often develop resistance to surveillance by endogenous immune cells, which include natural killer (NK) cells. Ex vivo activated and/or expanded NK cells demonstrate cytotoxicity against various tumor cells and are promising therapeutics for adoptive cancer immunotherapy. Genetic modification can further enhance NK effector cell activity or activation sensitization. Here, we evaluated the effect of the genetic deletion of ubiquitin ligase Casitas B-lineage lymphoma pro-oncogene-b (CBLB), a negative regulator of lymphocyte activity, on placental CD34+cell-derived NK (PNK) cell cytotoxicity against tumor cells.

Methods

Using CRISPR/Cas9 technology,CBLBwas knocked out in placenta-derived CD34+hematopoietic stem cells, followed by differentiation into PNK cells. Cell expansion, phenotype and cytotoxicity against tumor cells were characterized in vitro. The antitumor efficacy ofCBLBknockout (KO) PNK cells was tested in an acute myeloid leukemia (HL-60) tumor model in NOD-scidIL2R gammanull(NSG) mice. PNK cell persistence, biodistribution, proliferation, phenotype and antitumor activity were evaluated.

Results

94% ofCBLBKO efficacy was achieved using CRISPR/Cas9 gene editing technology.CBLBKO placental CD34+cells differentiated into PNK cells with high cell yield and >90% purity determined by CD56+CD3−cell identity. Ablation ofCBLBdid not impact cell proliferation, NK cell differentiation or phenotypical characteristics of PNK cells. When compared with the unmodified PNK control,CBLBKO PNK cells exhibited higher cytotoxicity against a range of liquid and solid tumor cell lines in vitro. On infusion into busulfan-conditioned NSG mice,CBLBKO PNK cells showed in vivo proliferation and maturation as evidenced by increased expression of CD16, killer Ig-like receptors and NKG2A over 3 weeks. Additionally,CBLBKO PNK cells showed greater antitumor activity in a disseminated HL60-luciferase mouse model compared with unmodified PNK cells.

Conclusion

CBLBablation increased PNK cell effector function and proliferative capacity compared with non-modified PNK cells. These data suggest that targetingCBLBmay offer therapeutic advantages via enhancing antitumor activities of NK cell therapies.
‘Value, values and valued’: a tripod for organisational ethics
Authors: Mohindra Raj
Published: March 2021

Public benefit corporations are National Health Service, that is, state, entities whose function to provide healthcare in discharge of public duties. If we regardvalue as the output of such organisations, it seems logical to connect the values of the organisation to thevalue produced by such organisations. But, on closer examination there are competing underlying logics in play: (1) those based on promoting organisational efficiency and efficacy; and (2) those based on the idea of building service provision around the clinician–patient relationship. Underlying these logics are differing value sets. These clash. Because of the clashing of underlying moral frameworks the connection between values andvalue becomes hard, if not impossible. This paper argues that (1) the clash in these moral frameworks must be addressed by the organisation rather than between individuals or groups of individuals within the organisation; (2) alloying duties within hybrid professionals submerges but does not resolve these conflicts; (3) one approach could be to impose on the organisation itself an ethical imperative to promote, enhance and protect from deterioration the welfare of the patients; (4) a board ethics committee is a possible organisational structure that could transparently and fairly balance clashes within the competing moral frameworks in a way that could reconcile the competing logics and (5) if such conflicts can be better resolved at the organisational level what the organisation must do to achieve its objectives will become clearer because what needs to be valued would naturally emerge connecting values,value and what is valued.
Nicotine dependence of cigarette and heated tobacco users in Japan, 2019: a cross-sectional analysis of the JASTIS Study
Authors: Lau Yan Kwan , Okawa Sumiyo , Meza Rafael , Katanoda Kota , Tabuchi Takahiro
Published: March 2021

Objectives

Japan is currently the biggest market of heated tobacco products (HTPs) in the world. Little is known about nicotine dependence among HTP users. Thus, the objective was to assess the association of type of tobacco use and time-to-first-use, a marker of nicotine dependence.

Methods

A cross-sectional analysis of the 2019 data from an internet cohort study was conducted. The analytical sample consisted of 2147 current (≥1 day use in the past 30 days) HTP and/or conventional cigarette users, aged 25+ years. Marginal structural binomial regression was used to estimate nicotine dependence prevalence ratios (PRs) for each category of tobacco use (exclusive daily cigarette, exclusive HTP (≥1 day), dual HTP+daily cigarette, dual HTP+non-daily cigarette), relative to exclusive, non-daily cigarette smoking.

Results

Using a 5 min cut-off for time-to-first-use, the prevalence of nicotine dependence was higher among dual users of HTP and daily cigarettes (PR=1.38; 95% CI: 1.05 to 1.82) and exclusive, daily cigarette users (PR=1.48; 95% CI: 1.15 to 1.91), relative to exclusive, non-daily cigarette users. However, nicotine dependence among exclusive HTP users, and dual HTP+non-daily cigarette users, did not differ from that of exclusive, non-daily cigarette users. When using 15 and 30 min cut-offs, all types of users, including exclusive HTP, had higher levels of nicotine dependence relative to exclusive, non-daily cigarette users.

Conclusions

Regardless of HTP use, daily cigarette users had higher prevalence of nicotine dependence compared with non-daily cigarette users. Exclusive HTP users had similar (or potentially higher) dependence compared with exclusive, non-daily cigarette users. Longitudinal studies are needed to interrogate the public health implications of growing HTP use worldwide.
Seasonal variation in air temperature drives reproductive phenology of entomophilous plants in a cool-temperate mire community
Authors: Ida Takashi Y. , Kudo Gaku
Published: March 2021

Phenological responses of plants to temperature dynamics are receiving attention due to the ongoing challenge with climate change. Most previous phenological studies have focused on flowering phenology rather than fruiting phenology. However, at mid-latitudes, the air temperature periodically changes during the growing period of plants. Hence, cool temperatures early and late in the growing period may affect reproductive success through pollination and fruit-development processes. To evaluate the linkages between reproductive phenology and success, we compared the phenologies, photosynthetic capacities, and fruit-set rates among 25 species within a cool-temperate community in northern Japan. The ambient temperature during the flowering periods of individual species increased with delays in flowering-onset time, whereas the ambient temperature during fruit-development periods was highest for species which bloomed in July. Fruit-set success among species was positively correlated with the ambient temperatures during the reproductive periods and with the photosynthetic capacity. Fruit production of early blooming species was limited by cool temperatures during the flowering period, presumably because of low pollinator activity, whereas that of late-blooming species was limited by cool temperatures during the fruit-development period because of slow fruit-development (i.e., sink limitation). Thus, limiting factors of fruit production varied depending on the flowering phenology of individual species within a community.
Charge screening in the Abelian Higgs model
Authors: Forgács Péter , Lukács Árpád
Published: March 2021

In the Abelian Higgs model electric (and magnetic) fields of external charges (and currents) are screened by the scalar field. In this contribution, complementing recent investigations of Ishihara and Ogawa, we present a detailed investigation of charge screening using a perturbative approach with the charge strength as an expansion parameter. It is shown how perfect global and remarkably good local screening can be derived from Gauss’ theorem, and the asymptotic form of the fields far from the sources. The perturbative results are shown to compare favourably to the numerical ones.
Reduction of Feynman integrals in the parametric representation II: reduction of tensor integrals
Authors: Chen Wen
Published: March 2021

In a recent paper by the author (Chen in JHEP 02:115, 2020), the reduction of Feynman integrals in the parametric representation was considered. Tensor integrals were directly parametrized by using a generator method. The resulting parametric integrals were reduced by constructing and solving parametric integration-by-parts (IBP) identities. In this paper, we furthermore show that polynomial equations for the operators that generate tensor integrals can be derived. Based on these equations, two methods to reduce tensor integrals are developed. In the first method, by introducing some auxiliary parameters, tensor integrals are parametrized without shifting the spacetime dimension. The resulting parametric integrals can be reduced by using the standard IBP method. In the second method, tensor integrals are (partially) reduced by using the technique of Gröbner basis combined with the application of symbolic rules. The unreduced integrals can further be reduced by solving parametric IBP identities.
QCD equation of state at finite chemical potentials for relativistic nuclear collisions
Authors: Monnai Akihiko , Schenke Björn , Shen Chun
Published: March 2021

We review the equation of state of QCD matter at finite densities. We discuss the construction of the equation of state with net baryon number, electric charge, and strangeness using the results of lattice QCD simulations and hadron resonance gas models. Its application to the hydrodynamic analyses of relativistic nuclear collisions suggests that the interplay of multiple conserved charges is important in the quantitative understanding of the dense nuclear matter created at lower beam energies. Several different models of the QCD equation of state are discussed for comparison.
Taxes, Mispricing, or the Agency Cost of Managerial Discretion? Evidence from Corporation to REIT Conversions
Authors: Gopal Naresh , Mateti Ravi S. , Nguyen Duong , Vasudevan Gopola
Published: March 2021

We study the effect of change in the organizational structure from a corporation to a real estate investment trust (REIT) on the firm value. Changing the organizational structure from a corporation to a REIT could result in an increase in the firm value, and some companies may be motivated to change their organizational structure because of this. We examine three possible sources of gains in the firm value from such a change in the organizational structure. They are the potential tax savings, reduction in agency costs of managerial discretion, and increase in the price multiples after the conversion. We examine the changes in the firm value of firms that announce conversion to a REIT during 1990–2016. We find that the announcement period returns are positive and strongly significant. Consistent with the tax hypothesis, the announcement period returns are positively related to the effective tax rate of the sample firms. Consistent with the managerial discretion hypothesis, the announcement period returns are positively related to the level of free cash flow of low growth firms. Consistent with the mis-valuation hypothesis, the announcement period returns are higher when REIT valuations are higher relative to the sample firms.
L∞-actions of Lie algebroids
Authors: Brahic Olivier , Zambon Marco
Published: March 2021

We consider homotopy actions of a Lie algebroid on a graded manifold, defined as suitable [Formula: see text]-algebra morphisms. On the “semi-direct product” we construct a homological vector field that projects to the Lie algebroid. Our main theorem states that this construction is a bijection. Since several classical geometric structures can be described by homological vector fields as above, we can display many explicit examples, involving Lie algebroids (including extensions, representations up to homotopy and their cocycles) as well as transitive Courant algebroids.