bluuebunny/crossref_metadata_2025 huggingface dataset:
Extrapolation of Adult Efficacy to Pediatric Patients With Chemotherapy‐Induced Nausea and Vomiting
Authors: Momper Jeremiah D. , Heinrichs M. Tobias , Krudys Kevin , Griebel Donna , Kumar Shaun , Kim Insook , Mehrotra Nitin , Mulberg Andrew E. , Garimella Narayana , Nelson Robert , Reaman Gregory , Sinha Vikram , Yao Lynne , Zineh Issam , Burckart Gilbert , Sachs Hari , Mulugeta Yeruk
Published: January 2020

Chemotherapy‐induced nausea and vomiting (CINV) is a common treatment‐related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unnecessary clinical trials, improve efficiency, and increase the likelihood of success in obtaining a pediatric indication. The acceptability of the use of extrapolation depends on a series of evidence‐based assumptions regarding the similarity of disease, response to intervention, and exposure‐response relationships between adult and pediatric patients. This study evaluated publicly available summaries of data submitted to the US Food and Drug Administration for drugs approved for CINV to assess the feasibility of extrapolation for future development programs. Extracted data included trial design, emetogenic potential of chemotherapy, primary end points, participant enrollment criteria, and antiemetic pharmacokinetics. Adult and pediatric clinical trial designs for assessment of efficacy and safety shared key design elements. Antiemetic drugs found to be efficacious in adults were also efficacious in pediatric patients. Systemic drug concentrations at approved doses were similar for ondansetron, granisetron, and aprepitant, but an exposure‐response analysis of palonosetron in children suggested that higher palonosetron systemic exposure is necessary for the prevention of CINV in the pediatric population. For 5‐hydroxytryptamine‐3 and neurokinin‐1 receptor antagonist antiemetic drugs, efficacy in adults predicts efficacy in children, supporting the extrapolation of effectiveness of an antiemetic product in children from adequate and well‐controlled studies in adult patients with CINV.
Regulation of IgE by T follicular helper cells
Authors: Gowthaman Uthaman , Chen Jennifer S. , Eisenbarth Stephanie C.
Published: January 2020

Allergies to food and environmental antigens have steeply grown to epidemic proportions. IgE antibodies are key mediators of allergic disease, including life-threatening anaphylaxis. There is now compelling evidence that one of the hallmarks of anaphylaxis-inducing IgE molecules is their high affinity for allergen, and the cellular pathway to high-affinity IgE is typically through sequential switching of IgG B cells. Further, in contrast to the previously held paradigm that a subset of CD4+ T cells called Th2 cells promotes IgE responses, recent studies suggest that T follicular helper cells are crucial for inducing anaphylactic IgE. Here we discuss recent studies that have enabled us to understand the nature, induction, and regulation of this enigmatic antibody isotype in allergic sensitization.
Rat IgG mediated circulatory cell depletion in mice requires mononuclear phagocyte system and is facilitated by complement
Authors: Sun Donglei , Sun Peng , He Shenghu , Shi Meiqing
Published: January 2020

Application of exogenous Abs targeting cell surface Ags has been widely used as an experimental approach to induce cell depletion or to inhibit receptor functionality. Moreover, Ab therapy is emerging as one of the mainstream strategies for cancer treatment. Previous studies on the mechanisms of Ab-mediated cell depletion mainly employed Abs from the same species as the research subject. However, there has been a recent trend toward using xenogeneic (cross-species) Abs to achieve cell depletion or block receptor-ligand interactions; with rat Abs used in mice being the most common approach. Considering the molecular differences in Abs from different species, the mechanism(s) of xenogeneic Ab-mediated cell depletion is likely to be different than species-matched Ab supplementation. The current work describes our efforts to identify the mechanism of rat anti-mouse Ly6G (clone: 1A8) mAb mediated depletion of mouse neutrophils. The results showed that neutrophils circulating in the blood but not those in the bone marrow are depleted, and depletion depends on mononuclear phagocyte system, especially liver Kupffer cells that efficiently capture and phagocytize targeted cells. Interestingly, whereas species-matched Ab depletion does not require complement functionality, we found that complement activation significantly facilitates cross-species neutrophil depletion. Finally, we found that some rat mAbs (anti-C5aR, anti-CD11a, anti-CD11b, and anti-VLA4) used to block cell surface receptors also induce cell depletion. Thus, our work strongly recommends controlling for cell depletion effect when using these Abs for receptor blockade purposes.
A new office‐based procedure for treatment of snoring: The S.I.Le.N.C.E. study
Authors: Friedman Michael , Gillespie M. Boyd , Shabdiz Faramarz A. , Hiltzik David H. , Meyer Ted A. , Ahn Jeffrey , Catalano Peter J. , Joseph Ninos J.
Published: January 2020

Objective

Demonstrate the safety and effectiveness of palatal foreshortening and stiffening in reducing snoring severity in nonobstructive sleep apnea (non‐OSA) patients complaining of chronic disruptive snoring.

Methods

In a US‐based 8‐center, open‐label, prospective, single‐arm cohort study, 52 consenting adults with chronic disruptive snoring (snoring impacting a patient's life and causing patient or bed partner to seek medical intervention) were treated via office‐based placement of resorbable, bidirectional, barbed suture implants into the soft palate under local anesthesia. Prior to intervention, home sleep tests (HSTs) were performed to rule out OSA and to document snoring noise level. Both subject and their bed/sleep partners (also consented) completed questionnaires including: bed/sleep partner's scored visual analog scale (VAS) for subjects' snoring severity, and subject scoring for Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Following intervention, HSTs, VAS, ESS and PSQI were repeated at 30, 90 and 180 days.

Results

Mean baseline bed/sleep partner VAS was 7.81 ± 1.59. Mean postimplant VAS scores decreased significantly at each measured interval; to 5.77±2.35 (P < .001) at 30 days, 4.48 ± 1.81 (P < .001) at 90 days, and 5.40 ± 2.28 (P < .001) at 180 days. Post treatment improvements in daytime sleepiness and QOL were also observed. Two partial extrusions were reported. No further adverse events were identified.

Conclusion

The current study demonstrates the safety and efficacy of the Elevoplasty procedure in reducing snoring severity over a follow‐up period of 6 months.

Level of Evidence

2b
Deficits in Muscle Strength and Physical Performance Influence Physical Activity in Sarcopenic Children After Liver Transplantation
Authors: Ooi Poh Hwa , Mazurak Vera C. , Siminoski Kerry , Bhargava Ravi , Yap Jason Y. K. , Gilmour Susan M. , Mager Diana R.
Published: January 2020

Sarcopenia is a muscle disease characterized by reduced skeletal muscle mass (SMM), muscle strength, and physical performance. Reduced SMM has been identified in children after liver transplantation (LT), but no information related to muscle strength/physical performance or lifestyle factors contributing to sarcopenia is available. We hypothesized that sarcopenia, as determined by measures of SMM, muscle strength, and physical performance, is highly prevalent in children after LT and is related to poor diet quality (DQ) and physical inactivity. A cross‐sectional study in post‐LT children (n = 22) and age‐matched healthy controls (n = 47) between the ages of 6 and 18 years examining body composition (dual energy X‐ray absorptiometry and multiple skinfold), measures of muscle strength (handgrip, sit‐to‐stand, and push‐ups), physical performance (6‐minute walk test and stair climb test), diet (3‐day food intake), and physical activity (accelerometer) was conducted. Low muscle strength/physical performance and SMM (SMM z scores ≤−1.5) were defined by values 2 standard deviations below the mean values for age‐ and sex‐matched controls. Sarcopenia occurred in 36% of children who underwent LT, and they had significantly lower scores for muscle strength (sit‐to‐stand and push‐up tests) and physical performance (stair climb test) than controls (P < 0.05). Deficits in physical performance in children with sarcopenia were predominantly revealed by longer stair climbing times (P = 0.03), with no differences in other muscle tests. Low SMM, muscle strength, and physical performance were associated with a lower amount of time spent in fairly and very active physical activity, but no associations with DQ were found. Sarcopenia is highly prevalent in children after LT and is related to lower moderate‐to‐vigorous physical activity. Development of effective rehabilitation strategies to treat sarcopenia are needed in post‐LT children.
Kelp Forest Zooplankton, Forage Fishes, and Juvenile Salmonids of the Northeast Pacific Nearshore
Authors: Shaffer J. Anne , Munsch Stuart H. , Cordell Jeffery R.
Published: January 2020

Kelp forests are an important ecological component of temperate coastal systems that are sensitive to anthropogenic disturbance and are in decline in many locations globally. In the northeastern Pacific Ocean off the coast of Washington, USA, bull kelp Nereocystis luetkeana forests are seasonally used by juvenile salmonids and forage fishes; however, details on ecosystem functional linkages for forage fishes and salmonids are not well quantified. Using a zooplankton drop net and snorkel surveys for fishes, we sampled two bull kelp forests across multiple years. Our goal was to quantify differences in the communities of zooplankton, juvenile salmonids (Chinook Salmon Oncorhynchus tshawytscha and Coho Salmon O. kisutch), and forage fishes (Pacific Herring Clupea pallasii, Surf Smelt Hypomesus pretiosus, and Pacific Sand Lance Ammodytes hexapterus) between kelp forests and adjacent nonkelp (open-water) habitats. We tested the hypothesis that zooplankton common in the diets of surface-oriented forage fishes and juvenile salmonids would be more abundant in kelp than in open water. At the overall assemblage level of organization, kelp and open-water habitats had similarly abundant and diverse zooplankton communities. However, decapods and phytal-associated harpacticoid copepods within this assemblage (i.e., groups that are an important component of fish diets) were significantly more abundant in kelp forests than in open-water habitat. Greater presence and abundance of zooplankton, juvenile salmonids, and forage fishes in kelp forests compared to adjacent open-water habitats suggest that kelp forests are important for culturally and economically valuable forage fishes and salmonids and warrant further study to define and conserve their ecosystem function.
PET Molecular Imaging of Phosphodiesterase 10A: An Early Biomarker of Huntington's Disease Progression
Authors: Fazio Patrik , Fitzer‐Attas Cheryl J. , Mrzljak Ladislav , Bronzova Juliana , Nag Sangram , Warner John H. , Landwehrmeyer Bernhard , Al‐Tawil Nabil , Halldin Christer , Forsberg Anton , Ware Jennifer , Dilda Valentina , Wood Andrew , Sampaio Cristina , Varrone Andrea ,   for the PEARL‐HD and LONGPDE10 study collaborators
Published: January 2020

Background

Changes in phosphodiesterase 10A enzyme levels may be a suitable biomarker of disease progression in Huntington's disease.

Objectives

To evaluate phosphodiesterase 10A PET imaging as a biomarker of HD progression using the radioligand, [18F]MNI‐659.

Methods

The cross‐sectional study (NCT02061722) included 45 Huntington's disease gene‐expansion carriers stratified into four disease stages (early and late premanifest and Huntington's disease stages 1 and 2) and 45 age‐ and sex‐matched healthy controls. The primary analysis compared striatal and pallidal phosphodiesterase 10A availability between Huntington's disease gene‐expansion carriers and healthy controls as assessed by [18F]MNI‐659 binding. We assessed changes in phosphodiesterase 10A expression using several PET methodologies and compared with previously proposed measures of Huntington's disease progression (PET imaging of D2/3 receptors and anatomical volume loss on MRI). The longitudinal follow‐up study (NCT02956148) continued evaluation of phosphodiesterase 10A availability in 35 Huntington's disease gene‐expansion carriers at a mean of 18 months from baseline of the cross‐sectional study.

Results

Primary analyses revealed that phosphodiesterase 10A availability in caudate, putamen, and globus pallidus was significantly lower in Huntington's disease gene‐expansion carriers versus healthy controls across all stages. Striatal and pallidal phosphodiesterase 10A availability progressively declined in the premanifest stages and appeared to plateau between stages 1 and 2. The percentage decline of phosphodiesterase 10A availability measured cross‐sectionally between Huntington's disease gene‐expansion carriers and healthy controls was greater than that demonstrated by D2/3 receptor availability or volumetric changes. Annualized rates of phosphodiesterase 10A change showed a statistically significant decline between the cross‐sectional study and follow‐up.

Conclusions

[18F]MNI‐659 PET imaging is a biologically plausible biomarker of Huntington's disease progression that is more sensitive than the dopamine‐receptor and volumetric methods currently used. © 2020 International Parkinson and Movement Disorder Society
SCD rs41290540 single‐nucleotide polymorphism modifies miR‐498 binding and is associated with a decreased risk of coronary artery disease
Authors: Liu Zhou , Yin Xiaojian , Mai Hui , Li Guangning , Lin Zhijun , Jie Wanxin , Li Kanglan , Zhou Haihong , Wei Shouchao , Hu Li , Peng Wanjuan , Lin Jiajing , Yao Feng , Tao Hua , Xiong Xing‐dong , Li Keshen
Published: January 2020

Background

Atherosclerosis is the primary cause of coronary artery disease (CAD), and stearoyl‐CoA desaturase (SCD) is associated with atherosclerosis. However, the associations between variants of SCD and CAD have not yet been decided.

Methods

This study analyzed SCD rs41290540 single‐nucleotide polymorphism (SNP) in the 3′‐untranslated region for an association with a risk of CAD among the Chinese Han population. CAD patients and controls were genotyped for SNP rs41290540 in SCD by SNaPshot. The binding affinity of miR‐498 to rs41290540 was determined by a luciferase assay, and SCD expression was assessed using Western blot.

Results

A total of 969 CAD patients and 1,095 control subjects were involved in this study. The SCD rs41290540CC genotype is associated with a decreased risk of CAD compared with the AA genotype. Furthermore, the CC genotype is associated with lower serum total cholesterol (TC). Western blot analysis demonstrated that miR‐498 suppressed the expression of SCD. A luciferase assay confirmed that rs41290540 A>C variation in the SCD 3′UTR inhibits miR‐498 binding.

Conclusion

This study demonstrates that the SCD rs41290540 may be associated with a decreased risk of CAD, lower serum TC, and decreased miR‐498 binding.
Proton functional magnetic resonance spectroscopy in rodents
Authors: Just Nathalie
Published: January 2020

Proton functional magnetic resonance spectroscopy (1H‐fMRS) in the human brain is able to assess and quantify the metabolic response due to localized brain activity. Currently, 1H‐fMRS of the human brain is complementary to functional magnetic resonance imaging (fMRI) and a recommended technique at high field strengths (>7 T) for the investigation of neurometabolic couplings, thereby providing insight into the mechanisms underlying brain activity and brain connectivity. Understanding typical healthy brain metabolism during a task is expected to provide a baseline from which to detect and characterize neurochemical alterations associated with various neurological or psychiatric disorders and diseases. It is of paramount importance to resolve fundamental questions related to the regulation of neurometabolic processes. New techniques such as optogenetics may be coupled to fMRI and fMRS to bring more specificity to investigations of brain cell populations during cerebral activation thus enabling a higher link to molecular changes and therapeutic advances. These rather novel techniques are mainly available for rodent applications and trigger renewed interest in animal fMRS. However, rodent fMRS remains fairly confidential due to its inherent low signal‐to‐noise ratio and its dependence on anesthesia. For instance, the accurate determination of metabolic concentration changes during stimulation requires robust knowledge of the physiological environment of the measured region of interest linked to anesthesia in most cases. These factors may also have a strong influence on B0 homogeneity. Therefore, a degree of calibration of the stimulus strength and duration may be needed for increased knowledge of the underpinnings of cerebral activity. Here, we propose an early review of the current status of 1H‐fMRS in rodents and summarize current difficulties and future perspectives.
Different approaches to classroom environments based on teacher experience and effectiveness
Authors: Pressley Tim , Croyle Hannah , Edgar Madison
Published: January 2020

The purpose of this qualitative instrumental case study was to continue looking at the differences in classroom environments for different levels of teachers. Specifically, we wanted to focus on teacher perspectives of classroom management, relationships with students, motivating students, student risk‐taking within the classroom, and student self‐regulation. The three levels we looked at for this study included highly effective teachers, proficient teachers who have taught for more than 3 years, and new/developing teachers. The results found three major themes with differences in how teachers at each level approached classroom management, relationships with students, and student behaviors within the classroom. The student behaviors within the classroom included self‐regulation and risk‐taking. The results of this study provide researchers more information regarding the different stages of teaching, information to schools on ways to mentor teachers at each level of teaching, and information to teacher preparation programs on ways to help preservice teachers prepare for the classroom.
Synthesis of well‐defined block copolymer composed of flexible amphiphilic poly(ethylene glycol) and hydrophobic liquid crystalline segments by living coordination polymerization of allene derivatives and its application to thin film with perpendicularly oriented cylindrical nanostructure
Authors: Sakai Koyuki , Nishiyama Hiroki , Inagi Shinsuke , Tomita Ikuyoshi , Hibi Yusuke , Komura Motonori , Nose Keiji , Iyoda Tomokazu
Published: January 2020

A block copolymer composed of a flexible polar poly(ethylene glycol) (PEG) and a less polar liquid crystalline poly(allene) segments is prepared by the living coordination polymerization of an allene derivative possessing trans‐azobenzene‐containing mesogenic substituent by the use of a π‐allylnickel macroinitiator bearing PEG segment. The thin film of the block copolymer is prepared by the spin coating of its solution onto mica or silicon wafer which proves to possess perpendicularly oriented nanocylindrical microphase separated structures as supported by the differential calorimetric, polarized optical microscopic, grazing‐incidence small‐angle X‐ray scattering, transmission electron microscope, and atomic force microscope measurements.
Application of binocular visual navigation technique in diaphyseal fracture reduction
Authors: Du Hailong , Hu Lei , Hao Ming , Zhang Lihai
Published: January 2020

Background

Computer‐assisted surgical navigation techniques have shown promise; however, currently popular systems have limitations. This paper presents the characterization and application of a binocular visual navigation technique in diaphyseal fracture reduction.

Methods

A binocular visual tracker (MicronTracker) was introduced to reduce diaphyseal fractures. A transformation matrix was used to acquire the reduction parameters. A transverse diaphyseal fracture was used as a control group.

Results

Precision tests were performed with the binocular system using a simulation femoral model with a transverse fracture 12 times. All residual deformations were compared and P < 0.01.

Conclusions

The binocular visual navigation technique produces good results with advantages of flexibility and high positional accuracy and shows promise. The MicronTracker might lead to further application in the remote navigation field.
A functional‐model‐adjusted spatial scan statistic
Authors: Ahmed Mohamed‐Salem , Genin Michaël
Published: January 2020

This paper introduces a new spatial scan statistic designed to adjust cluster detection for longitudinal confounding factors indexed in space. The functional‐model‐adjusted statistic was developed using generalized functional linear models in which longitudinal confounding factors were considered to be functional covariates. A general framework was developed for application to various probability models. Application to a Poisson model showed that the new method is equivalent to a conventional spatial scan statistic that adjusts the underlying population for covariates. In a simulation study with single and multiple covariate models, we found that our new method adjusts the cluster detection procedure more accurately than other methods. Use of the new spatial scan statistic was illustrated by analyzing data on premature mortality in France over the period from 1998 to 2013, with the quarterly unemployment rate as a longitudinal confounding factor.
Extending Photoresponse to the Near‐Infrared Region for Inverted Perovskite Solar Cells by Using a Low‐Bandgap Electron Transporting Material
Authors: Wu Fei , Gao Wei , Zhu Linna , Lu Huiqiang , Yang Chuluo
Published: January 2020

Lead‐based organic–inorganic hybrid perovskite solar cells (PSCs) usually show an absorption edge around 800 nm, while the near‐infrared (NIR) wavelength beyond 800 nm cannot be utilized. Herein, a new indacenothiophene‐based electron transporting material (ETM), namely, ITCP‐M, is developed, which works to enhance electron extraction and electron transporting, and simultaneously extends photoresponses to the NIR region in MAPbI3‐based inverted PSCs. Notably, the ITCP‐M‐based device exhibits a prominent photoresponse beyond 800 nm as observed from the external quantum efficiency (EQE) spectra, contributing to enhanced short‐circuit current density (Jsc) without sacrificing the open‐circuit voltage and fill factor. As a result, inverted PSCs using ITCP‐M ETM delivers a high efficiency of 19.15%, representing one of the highest efficiencies in inverted PSCs using nonfullerene ETMs. This work provides a new and simple strategy to extend photoresponses to the NIR absorption region for MAPbI3‐based inverted PSCs that can significantly improve device performance.
Production asymmetry of ντ neutrinos and $$ {\overline{\nu}}_{\tau } $$ antineutrinos from a fixed target experiment SHiP
Authors: Maciuła Rafał , Szczurek Antoni , Zaremba Jakub , Babiarz Izabela
Published: January 2020

Abstract

We discuss how to calculate cross sections as well as rapidity, transverse momentum and energy distributions of ν

τ
and

$$ {\overline{\nu}}_{\tau } $$

ν
¯

τ

produced from the direct

$$ {D}_s^{\pm}\to {\nu}_{\tau }/{\overline{\nu}}_{\tau } $$

D
s
±

→

ν
τ

/

ν
¯

τ

and chain

$$ {D}_s^{\pm}\to {\tau}^{+}/{\tau}^{-}\to {\nu}_{\tau }/{\overline{\nu}}_{\tau } $$

D
s
±

→

τ
+

/

τ
−

→

ν
τ

/

ν
¯

τ

decays in p+96 Mo scattering with proton beam E
lab = 400 GeV i.e. at

$$ {\sqrt{s}}_{NN} $$

s

NN

= 27.4 GeV. The τ decays are simulated with the help of the Tauola code and include multiple decay channels of τ in amounts proportional to their branching ratios. In our calculations we include

$$ {D}_s^{\pm } $$

D
s
±

from charm fragmentation c →

$$ {D}_s^{+} $$

D
s
+

and

$$ \overline{c}\to {D}_s^{-} $$

c
¯

→

D
s
−

as well as those from subleading fragmentation of strange quarks/antiquarks s →

$$ {D}_s^{-} $$

D
s
−

and

$$ \overline{s}\to {D}_s^{+} $$

s
¯

→

D
s
+

. The

$$ s\ne \overline{s} $$

s
≠

s
¯

asymmetry of the strange quark content of proton is included. The different contributions to

$$ {D}_s^{+} $$

D
s
+

and

$$ {\nu}_{\tau }/{\overline{\nu}}_{\tau } $$

ν
τ

/

ν
¯

τ

are shown explicitly. We discuss and quantify a not discussed so far effect of asymmetries for production of ν

τ
and

$$ {\overline{\nu}}_{\tau } $$

ν
¯

τ

caused by subleading fragmentation mechanism and discuss related uncertainties. A potential measurement of the asymmetry is discussed. Estimates of a number of observed

$$ {\nu}_{\tau }/{\overline{\nu}}_{\tau } $$

ν
τ

/

ν
¯

τ

in the

$$ {\nu}_{\tau }/{\overline{\nu}}_{\tau } $$

ν
τ

/

ν
¯

τ

+208Pb reaction, with 2m long target are given with the help of the NuWro program. We refer also to the production of the high-energy (anti)neutrinos in the atmosphere.
Complexity for charged thermofield double states
Authors: Doroudiani Mehregan , Naseh Ali , Pirmoradian Reza
Published: January 2020

Abstract

We study Nielsen’s circuit complexity for a charged thermofield double state (cTFD) of free complex scalar quantum field theory in the presence of background electric field. We show that the ratio of the complexity of formation for cTFD state to the thermo- dynamic entropy is finite and it depends just on the temperature and chemical potential. Moreover, this ratio smoothly approaches the value for real scalar theory. We compare our field theory calculations with holographic complexity of charged black holes and confirm that the same cost function which is used for neutral case continues to work in presence of U(1) background field. For t > 0, the complexity of cTFD state evolves in time and contrasts with holographic results, it saturates after a time of the order of inverse temper- ature. This discrepancy can be understood by the fact that holographic QFTs are actually strong interacting theories, not free ones.
Transplanckian censorship and the local swampland distance conjecture
Authors: Draper Patrick , Farkas Szilard
Published: January 2020

Abstract

The swampland distance conjecture (SDC) addresses the ability of effective field theory to describe distant points in moduli space. It is natural to ask whether there is a local version of the SDC: is it possible to construct local excitations in an EFT that sample extreme regions of moduli space? In many cases such excitations exhibit horizons or instabilities, suggesting that there are bounds on the size and structure of field excitations that can be achieved in EFT. Static bubbles in ordinary Kaluza-Klein theory provide a simple class of examples: the KK radius goes to zero on a smooth surface, locally probing an in- finite distance point, and the bubbles are classically unstable against radial perturbations. However, it is also possible to stabilize KK bubbles at the classical level by adding flux. We study the impact of imposing the Weak Gravity Conjecture (WGC) on these solutions, finding that a rapid pair production instability arises in the presence of charged matter with q/m ≳ 1. We also analyze 4d electrically charged dilatonic black holes. Small curvature at the horizon imposes a bound log (M

BH
) ,≳ |∆𝜙|, independent of the WGC, and the bound can be strengthened if the particle satisfying the WGC is sufficiently light. We conjecture that quantum gravity in asymptotically flat space requires a general bound on large localized moduli space excursions of the form |∆𝜙| ≲ | log(RΛ)|, where R is the size of the minimal region enclosing the excitation and Λ
−1 is the short-distance cutoff on local EFT. The bound is qualitatively saturated by the dilatonic black holes and Kaluza-Klein monopoles.
On Brannan’s Conjecture
Authors: Szász Róbert
Published: January 2020

We prove the Brannan conjecture for particular values of the parameter. The basic tool of the study is an integral representation published in a recent work (Barnard et al., in Proc Am Math Soc 143(5):2117–2128, 2015).
Red meat, poultry and fish consumption and risk of diabetes: a 9 year prospective cohort study of the China Kadoorie Biobank
Authors:   on behalf of the China Kadoorie Biobank collaborative group, Du Huaidong , Guo Yu , Bennett Derrick A. , Bragg Fiona , Bian Zheng , Chadni Mahmuda , Yu Canqing , Chen Yiping , Tan Yunlong , Millwood Iona Y. , Gan Wei , Yang Ling , Yao Pang , Luo Guojin , Li Jianguo , Qin Yulu , Lv Jun , Lin Xu , Key Tim , Chen Junshi , Clarke Robert , Li Liming , Chen Zhengming
Published: January 2020

Aims/hypothesis

Previous evidence linking red meat consumption with diabetes risk mainly came from western countries, with little evidence from China, where patterns of meat consumption are different. Moreover, global evidence remains inconclusive about the associations of poultry and fish consumption with diabetes. Therefore we investigated the associations of red meat, poultry and fish intake with incidence of diabetes in a Chinese population.

Methods

The prospective China Kadoorie Biobank recruited ~512,000 adults (59% women, mean age 51 years) from ten rural and urban areas across China in 2004–2008. At the baseline survey, a validated interviewer-administered laptop-based questionnaire was used to collect information on the consumption frequency of major food groups including red meat, poultry, fish, fresh fruit and several others. During ~9 years of follow-up, 14,931 incidences of new-onset diabetes were recorded among 461,036 participants who had no prior diabetes, cardiovascular diseases or cancer at baseline. Cox regression analyses were performed to calculate adjusted HRs for incident diabetes associated with red meat, poultry and fish intake.

Results

At baseline, 47.0%, 1.3% and 8.9% of participants reported a regular consumption (i.e. ≥4 days/week) of red meat, poultry and fish, respectively. After adjusting for adiposity and other potential confounders, each 50 g/day increase in red meat and fish intake was associated with 11% (HR 1.11 [95% CI 1.04, 1.20]) and 6% (HR 1.06 [95% CI 1.00, 1.13]) higher risk of incident diabetes, respectively. For both, the associations were more pronounced among men and women from urban areas, with an HR (95% CI) of 1.42 (1.15, 1.74) and 1.18 (1.03, 1.36), respectively, per 50 g/day red meat intake and 1.15 (1.02, 1.30) and 1.11 (1.01, 1.23), respectively, per 50 g/day fish intake. There was no significant association between diabetes and poultry intake, either overall (HR 0.96 [95% CI 0.83, 1.12] per 50 g/day intake) or in specific population subgroups.

Conclusions/interpretation

In Chinese adults, both red meat and fish, but not poultry, intake were positively associated with diabetes risk, particularly among urban participants. Our findings add new evidence linking red meat and fish intake with cardiometabolic diseases.

Data availability

Details of how to access the China Kadoorie Biobank data and rules of China Kadoorie Biobank data release are available from www.ckbiobank.org/site/Data+Access.
Anthropometric clothing measurements from 3D body scans
Authors: Yan Song , Wirta Johan , Kämäräinen Joni-Kristian
Published: January 2020

We propose a full processing pipeline to acquire anthropometric measurements from 3D measurements. The first stage of our pipeline is a commercial point cloud scanner. In the second stage, a pre-defined body model is fitted to the captured point cloud. We have generated one male and one female model from the SMPL library. The fitting process is based on non-rigid iterative closest point algorithm that minimizes overall energy of point distance and local stiffness energy terms. In the third stage, we measure multiple circumference paths on the fitted model surface and use a nonlinear regressor to provide the final estimates of anthropometric measurements. We scanned 194 male and 181 female subjects, and the proposed pipeline provides mean absolute errors from 2.5 to 16.0 mm depending on the anthropometric measurement.
The noneffectivity of Arslanov’s completeness criterion and related theorems
Authors: Terwijn Sebastiaan A.
Published: January 2020

We discuss the (non)effectivity of Arslanov’s completeness criterion. In particular, we show that a parameterized version, similar to the recursion theorem with parameters, fails. We also discuss the effectivity of another extension of the recursion theorem, namely Visser’s ADN theorem, as well as that of a joint generalization of the ADN theorem and Arslanov’s completeness criterion.
Assessment of trapped powder removal and inspection strategies for powder bed fusion techniques
Authors: Hunter Luke W. , Brackett David , Brierley Nick , Yang Jian , Attallah Moataz M.
Published: January 2020

The issue of trapped powder within a part made using powder bed fusion additive manufacturing (AM) is one of the ‘dirty secrets’ of AM, yet it has not received significant attention by the research community. Trapped powders limit the application of AM for complex geometries, including heat exchangers and dies with conformal cooling channels. Being able to detect and remove trapped powder from the build is a necessary step to avoid downstream processing and performance challenges. In this work, ‘powder challenge geometries’ with complex internal features were fabricated via laser powder bed fusion (L-PBF) and electron beam selective melting (EBSM) and were used to assess the effectiveness of several powder removal and inspection methods. Hand-held ultrasonic polishing was explored as a powder removal technique and was shown to effectively clear extremely elongated channels that grit-blasting (the current industry standard) cannot clear. X-ray computed tomography (XCT) and weighing were used to inspect and quantitatively assess the effectiveness of powder removal techniques on the challenge geometries. Using the lesser known ‘vacuum boiling’ powder removal process and the more common ultrasonic bathing process, trapped L-PBF powder was easily removed from the deep channels. Conversely, trapped EBSM powder was difficult to remove using ultrasonic polishing as the powder was sintered inside the channels. It was shown that the powder recovered by the ultrasonic polishing process had size distributions, surface chemistry, morphology and porosity similar to the virgin powder. It is suggested, on these bases, that the recovered powder could likely be recycled without detrimental effects on the process operation.
Counting Induced Subgraphs: A Topological Approach to #W[1]-hardness
Authors: Roth Marc , Schmitt Johannes
Published: January 2020

We investigate the problem $$\#{{\mathsf {IndSub}}}(\varPhi )$$

#
IndSub
(
Φ
)

of counting all induced subgraphs of size k in a graph G that satisfy a given property $$\varPhi $$
Φ
.
This continues the work of Jerrum and Meeks who proved the problem to be $$\#{{\mathrm {W[1]}}}$$

#

W
[
1
]

-hard for some families of properties which include (dis)connectedness [JCSS 15] and even- or oddness of the number of edges [Combinatorica 17]. Using the recent framework of graph motif parameters due to Curticapean, Dell and Marx [STOC 17], we discover that for monotone properties $$\varPhi $$
Φ
, the problem $$\#{{\mathsf {IndSub}}}(\varPhi )$$

#
IndSub
(
Φ
)

is hard for $$\#{{\mathrm {W[1]}}}$$

#

W
[
1
]

if the reduced Euler characteristic of the associated simplicial (graph) complex of $$\varPhi $$
Φ
is non-zero. This observation links $$\#{{\mathsf {IndSub}}}(\varPhi )$$

#
IndSub
(
Φ
)

to Karp’s famous Evasiveness Conjecture, as every graph complex with non-vanishing reduced Euler characteristic is known to be evasive. Applying tools from the “topological approach to evasiveness” which was introduced in the seminal paper of Khan, Saks and Sturtevant [FOCS 83], we prove that $$\#{{\mathsf {IndSub}}}(\varPhi )$$

#
IndSub
(
Φ
)

is $$\#{{\mathrm {W[1]}}}$$

#

W
[
1
]

-hard for every monotone property $$\varPhi $$
Φ
that does not hold on the Hamilton cycle as well as for some monotone properties that hold on the Hamilton cycle such as being triangle-free or not k-edge-connected for $$k > 2$$

k
>
2

. Moreover, we show that for those properties $$\#{{\mathsf {IndSub}}}(\varPhi )$$

#
IndSub
(
Φ
)

can not be solved in time $$f(k)\cdot n^{o(k)}$$

f

(
k
)

·

n

o
(
k
)

for any computable function f unless the Exponential Time Hypothesis (ETH) fails. In the final part of the paper, we investigate non-monotone properties and prove that $$\#{{\mathsf {IndSub}}}(\varPhi )$$

#
IndSub
(
Φ
)

is $$\#{{\mathrm {W[1]}}}$$

#

W
[
1
]

-hard if $$\varPhi $$
Φ
is any non-trivial modularity constraint on the number of edges with respect to some prime q or if $$\varPhi $$
Φ
enforces the presence of a fixed isolated subgraph.
An artificial neural network model for the unary description of pure substances and its application on the thermodynamic modelling of pure iron
Authors: Länge Maximilian
Published: January 2020

The aim of this work is to introduce a novel approach for the universal description of the thermodynamic functions of pure substances on the basis of artificial neural networks. The proposed approximation method is able to describe the thermodynamic functions ($$C_{p}(T), S(T), H(T)-H(T_{\mathrm{ref}}), G(T)$$

C
p

(
T
)

,
S

(
T
)

,
H

(
T
)

-
H

(

T
ref

)

,
G

(
T
)

) of the different phases of unary material systems in a wide temperature range (between 0 and 6000 K). Phase transition temperatures and the respective enthalpies of transformation, which are computationally determined by the minimization of the Gibbs free energy, are also approximated. This is achieved by using artificial neural networks as models for the thermodynamic functions of the individual phases and by expressing the thermodynamic quantities in terms of the free network parameters. The resulting expressions are then optimized with machine learning algorithms on the basis of measurement data. A physical basis for the resulting approximation is given by the use of, among others, Planck–Einstein functions as activation function of the neurons of the network. This article provides a description of the method and as an example of a specific application the approximation of the thermodynamic functions of the different phases of pure iron. The article focuses on the problem of the representation of thermodynamic data and their practical application.
Exploring the role of oral microorganisms in the pathogenesis of mucositis by assessing their impact on metabolic activity and reproductive capacity of epithelial cells in vitro
Authors: Haverman Thijs M. , Laheij Alexa M. G. A. , Nie Min , Deng Dong M. , Raber-Durlacher Judith E. , de Soet Johannes J. , Rozema Frederik R.
Published: January 2020

Purpose

Clinical and in vitro studies showed selected oral microorganisms to be related to delayed wound healing and ulcerative oral mucositis. However, it is not known whether this effect is due to reduced metabolism and/or the reduced reproductive capacity of epithelial cells. Therefore, we studied the influence of the oral microorganisms Porphyromonas gingivalis, Candida glabrata, and Candida kefyr on cell metabolism and reproductive capacity of oral epithelial cells, aimed to further unravel the pathogenesis of oral mucositis.

Methods

Oral epithelial cells were exposed to different concentrations of P. gingivalis, C. glabrata, and C. kefyr as mono-infections or mixed together. An MTT assay was performed to determine the effect on cell metabolism. A clonogenic assay was used to study the effect on the reproductive capacity of oral epithelial cells.

Results

The metabolism of oral epithelial cells was reduced when the microorganisms were present in high concentrations: P. gingivalis at a multiplicity of infection (MOI) of 1000 and the Candida spp. at MOI 100. No statistical difference was observed in the ability of a single epithelial cell to grow into a colony of cells between control and P. gingivalis, C. glabrata, and C. kefyr, independent of the concentrations and combinations used.

Conclusion

P. gingivalis, C. glabrata, and C. kefyr lowered the metabolic activity of oral epithelial cells in high concentrations, yet they did not influence the reproductive capacity of epithelial cells. Their impact on ulcerative oral mucositis is likely due to an effect on the migration, proliferation, and metabolism of epithelial cells.
Emerging therapies for PBC
Authors: Chascsa David Maxwell Hunter , Lindor Keith Douglas
Published: January 2020

Primary biliary cholangitis is an uncommon cholestatic liver disease predominantly affecting middle-aged women. Left untreated, there is a high risk of progression to end-stage liver disease. Few treatment options exist. To date, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are the only medical therapies approved for use, other than symptomatic treatments and liver transplantation, the latter of which is reserved for those developing complications of cirrhosis or with intractable pruritus. UDCA improves outcomes, but many patients do not adequately respond. OCA therapy may improve response, but long-term data are limited. New therapies are desperately needed, but evaluation has been limited by the fact that the disease is heterogeneous, hard end points take years to develop, and there are different criteria in use for determining therapeutic response based on surrogate biomarkers. Fibrates appear to be the most promising new therapy and have beneficially affected surrogate end points and are beginning to show improvement in clinical end points.
Three-year pot culture of Epipactis helleborine reveals autotrophic survival, without mycorrhizal networks, in a mixotrophic species
Authors: May Michał , Jąkalski Marcin , Novotná Alžběta , Dietel Jennifer , Ayasse Manfred , Lallemand Félix , Figura Tomáš , Minasiewicz Julita , Selosse Marc-André
Published: January 2020

Some mixotrophic plants from temperate forests use the mycorrhizal fungi colonizing their roots as a carbon source to supplement their photosynthesis. These fungi are also mycorrhizal on surrounding trees, from which they transfer carbon to mixotrophic plants. These plants are thus reputed difficult to transplant, even when their protection requires it. Here, we take profit of a successful ex situ pot cultivation over 1 to 3 years of the mixotrophic orchidEpipacis helleborineto investigate its mycorrhizal and nutrition status. Firstly, compared with surrounding autotrophic plants, it did not display the higher N content and higher isotopic (13C and15N) abundance that normally feature mixotrophic orchids because they incorporate N-,13C-, and15N-rich fungal biomass. Second, fungal barcoding by next-generation sequencing revealed that the proportion of ectomycorrhizal fungi (expressed as percentage of the total number of either reads or operational taxonomic units) was unusually low compared withE. helleborinegrowing in situ: instead, we found a high percentage of rhizoctonias, the usual mycorrhizal partners of autotrophic orchids. Altogether, this supports autotrophic survival. Added to the recently published evidence that plastid genomes of mixotrophic orchids have intact photosynthetic genes, this suggests that at least some of them have abilities for autotrophy. This adds to the ecological plasticity of mixotrophic plants, and may allow some reversion to autotrophy in their evolution.
Changing contribution of smoking to the sex differences in life expectancy in Europe, 1950–2014
Authors: Janssen Fanny
Published: January 2020

This article provides a detailed and overarching illustration of the contribution of smoking to sex differences in life expectancy at birth (e0) in Europe, focusing on changes over time and differences between both European countries and European regions. For this purpose, the sex difference in e0 for 31 European countries over the 1950–2014 period was decomposed into a smoking- and a non-smoking-related part, using all-cause mortality data and indirectly estimated smoking-attributable mortality rates by age and sex, and a formal decomposition analysis. It was found that smoking-attributable mortality contributed, on average, 3 years (43.5%) to the 7-year life expectancy difference between women and men in 2014. This contribution, was largest in 1995, at 5.2 out of 9.0 years, and subsequently declined in parallel with the average sex difference in life expectancy. The average contribution of smoking-attributable mortality was especially large in North-Western Europe around 1975; in Southern Europe around 1985; and in Eastern Europe around 1990–1995, when smoking-attributable mortality reached maximum levels among men, but was still low among women. The observed parallel decline from 1995 onwards in the sex differences in e0 and the absolute contribution of smoking to this sex difference suggests that this recent decline in the sex difference in e0 can be almost fully explained by historical changes in sex differences in smoking, and, consequently, smoking-attributable mortality. In line with the progression of the smoking epidemic, the sex differences in life expectancy in Europe are expected to further decline in the future.
A novel learning-based feature recognition method using multiple sectional view representation
Authors: Shi Peizhi , Qi Qunfen , Qin Yuchu , Scott Paul J. , Jiang Xiangqian
Published: January 2020

In computer-aided design (CAD) and process planning (CAPP), feature recognition is an essential task which identifies the feature type of a 3D model for computer-aided manufacturing (CAM). In general, traditional rule-based feature recognition methods are computationally expensive, and dependent on surface or feature types. In addition, it is quite challenging to design proper rules to recognise intersecting features. Recently, a learning-based method, named FeatureNet, has been proposed for both single and multi-feature recognition. This is a general purpose algorithm which is capable of dealing with any type of features and surfaces. However, thousands of annotated training samples for each feature are required for training to achieve a high single feature recognition accuracy, which makes this technique difficult to use in practice. In addition, experimental results suggest that multi-feature recognition part in this approach works very well on intersecting features with small overlapping areas, but may fail when recognising highly intersecting features. To address the above issues, a deep learning framework based on multiple sectional view (MSV) representation named MsvNet is proposed for feature recognition. In the MsvNet, MSVs of a 3D model are collected as the input of the deep network, and the information achieved from different views are combined via the neural network for recognition. In addition to MSV representation, some advanced learning strategies (e.g. transfer learning, data augmentation) are also employed to minimise the number of training samples and training time. For multi-feature recognition, a novel view-based feature segmentation and recognition algorithm is presented. Experimental results demonstrate that the proposed approach can achieve the state-of-the-art single feature performance on the FeatureNet dataset with only a very small number of training samples (e.g. 8–32 samples for each feature), and outperforms the state-of-the-art learning-based multi-feature recognition method in terms of recognition performances.