bluuebunny/crossref_metadata_2025 huggingface dataset:
A first, naturally occurring substitution at the second pyrethroid receptor of voltage‐gated sodium channel of Aedes aegypti
Authors: Itokawa Kentaro , Furutani Shogo , Takaoka Aki , Maekawa Yoshihide , Sawabe Kyoko , Komagata Osamu , Tomita Takashi , de Lima Filho José Luiz , Alves Luiz Carlos , Kasai Shinji
Published: February 2021

BACKGROUND

Aedes aegypti is a remarkably effective mosquito vector of epidemiologically important arboviral diseases including dengue fever, yellow fever and Zika. The present spread of resistance against pyrethroids, the primary insecticides used for mosquito control, in global populations of this species is of great concern. The voltage‐gated sodium channel (VGSC) in the nervous system is the known target site of pyrethroids in insects. Past studies have revealed several amino‐acid substitutions in this channel that confer pyrethroid resistance, which are known as knockdown resistance (kdr) mutations.

RESULTS

This study investigated a laboratory colony of Ae. aegypti, MCNaeg, established from larvae collected in Rio de Janeiro, Brazil in 2016. The MCNaeg colony showed strong resistance against pyrethroids without laboratory selection. Of the two VGSC gene haplotypes present within this colony, one harbored three known kdr mutations, V410L, V1016I, and F1534C, and the other harbored only the known F1534C mutation. In latter haplotype, we also found novel amino‐acid substations including V253F. Previous molecular modeling and electrophysiological studies suggest that this residue serves a pyrethroid‐sensing site in the second receptor, PyR2. Our genetical analysis showed that the haplotype harboring V253F and F1534C is associated with equal or slightly stronger resistance than the other triple kdr haplotype to both Type I and Type II pyrethroids.

CONCLUSION

The novel substitution V253F is potentially involved in pyrethroid resistance in Ae. aegypti. Further studies are needed to elucidate the role of this substitution in the pyrethroid susceptibility of VGSC.

© 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Murine cancer cachexia models replicate elevated catabolic pembrolizumab clearance in humans
Authors: Castillo Alyssa Marie M. , Vu Trang T. , Liva Sophia G. , Chen Min , Xie Zhiliang , Thomas Justin , Remaily Bryan , Guo Yizhen , Subrayan Uma L. , Costa Travis , Helms Timothy H. , Irby Donald J. , Kim Kyeongmin , Owen Dwight H. , Kulp Samuel K. , Mace Thomas A. , Phelps Mitch A. , Coss Christopher C.
Published: February 2021

Background

Monoclonal antibody (mAb) immune checkpoint inhibitor (ICI) therapies have dramatically impacted oncology this past decade. However, only about one‐third of patients respond to treatment, and biomarkers to predict responders are lacking. Recent ICI clinical pharmacology data demonstrate high baseline drug clearance (CL0) significantly associates with shorter overall survival, independent of ICI exposure, in patients receiving ICI mAb therapies. This suggests CL0 may predict outcomes from ICI therapy, and cachectic signalling may link elevated CL0 and poor response. Our aim was to determine if mouse models of cancer cachexia will be useful for studying these phenomena and their underlying mechanisms.

Methods

We evaluated pembrolizumab CL in the C26 and Lewis lung carcinoma mouse models of cancer cachexia. A single treatment of vehicle or pembrolizumab, at a dose of 2 or 10 mg/kg, was administered intravenously by tail vein injection. Pembrolizumab was quantified by an ELISA in serial plasma samples, and FcRn gene (Fcgrt) expression was assessed in liver using real‐time quantitative reverse transcription PCR. Non‐compartmental and mixed‐effects pharmacokinetics analyses were performed.

Results

We observed higher pembrolizumab CL0 and decreased Fcgrt expression in whole liver tissue from tumour‐bearing vs. tumour‐free mice. In multivariate analysis, presence of tumour, total murine IgG, muscle weight and Fcgrt expression were significant covariates on CL, and total murine IgG was a significant covariate on V1 and Q.

Conclusions

These data demonstrate increases in catabolic clearance of monoclonal antibodies observed in humans can be replicated in cachectic mice, in which Fcgrt expression is also reduced. Notably, FcRn activity is essential for proper antigen presentation and antitumour immunity, which may permit the study of cachexia's impact on FcRn‐mediated clearance and efficacy of ICI therapies.
Regeneration of Supported Ammonia Borane to Achieve Higher Yield
Authors: Hajari Animesh , Roy Binayak , Kumar Vinit , Bishnoi Ankita , Sharma Pratibha
Published: February 2021

Ammonia borane is considered as a potential hydrogen storage material due to its high hydrogen content, ease of handling, and moderate dehydrogenation temperature. The regeneration of ammonia borane (AB) is essential for its use as a sustainable hydrogen storage material. In the current work, we attempted to regenerate AB from the post heated product (spent fuel, i. e., products obtained after hydrogen release) through a digestion mediated B−O−C route. We have also demonstrated the dehydrogenation and regeneration compatibility with the use of a cost‐effective layered aluminosilicate support material, bentonite (gBen), and this facilitated both the dehydrogenation and regeneration processes. The isothermal dehydrogenation study suggested that the support material helped to improve the hydrogen release kinetics from AB at lower temperatures. During the regeneration process, gBen supported AB is observed to provide a higher yield (71 %) of the digested compound ammonium tetramethylborate (ATMB) as against post heated AB (with 35 % in case of pure AB to post AB to ATMB), which finally resulted in increasing the overall regeneration yield of AB. The regeneration of AB with high yield and purity is confirmed by 11B NMR and XRD analysis.
Intrinsic polarization coupling in 2D α‐In2Se3toward artificial synapse with multimode operations
Authors: Gao Jing , Zheng Yue , Yu Wei , Wang Yanan , Jin Tengyu , Pan Xuan , Loh Kian Ping , Chen Wei
Published: February 2021

Emulation of advanced synaptic functions of the human brain with electronic devices contributes an important step toward constructing high‐efficiency neuromorphic systems. Ferroelectric materials are promising candidates as synaptic weight elements in neural network hardware due to their controllable polarization states. However, the increased depolarization field at the nanoscale and the complex fabrication process of the traditional ferroelectric materials hamper the development of high‐density, low‐power, and highly sensitive synaptic devices. Here, we report the implementation of two‐dimensional (2D) ferroelectric α‐In2Se3as an active channel material to emulate typical synaptic functions. The α‐In2Se3‐based synaptic device features multimode operations, enabled by the coupled ferroelectric polarization under various voltage pulses applied at both drain and gate terminals. Moreover, the energy consumption can be reduced to ~ 1 pJ by using high‐κdielectric (Al2O3). The successful control of ferroelectric polarizations in α‐In2Se3and its application in artificial synapses are expected to inspire the implementation of 2D ferroelectric materials for future neuromorphic systems.
Comparison of Multipiscivore Foraging Success on Native and Invasive Prey Fish under Variable Light Intensities
Authors: Michels N. O. , Hrabik T. R. , Mensinger A. F.
Published: February 2021

Piscivorous fishes attack and consume a variety of prey; however, few studies have examined interactions of multiple predators with multiple prey species. The situational complexity of foraging at different times of day was explored by examining the interactions of paired native predators (BurbotLota lotaor Smallmouth BassMicropterus dolomieu) with either native (Mottled SculpinCottus bairdii) or invasive (Round GobyNeogobius melanostomus) benthic prey. The study allowed the comparison of a pursuit predator (Smallmouth Bass) and an ambush predator (Burbot). Trials were performed under natural relevant lighting conditions with downwelling light intensity and emission spectrum matched to the irradiance at a 10‐m depth in the St. Louis River estuary during the summer at night, civil twilight, sunrise, and midmorning. Smallmouth Bass were more active and initiated 1,510 reactions that resulted in the successful capture of 61 Round Goby and 103 Mottled Sculpin, whereas Burbot initiated 475 reactions resulting in 24 successful retentions, including 9 Round Goby and 15 Mottled Sculpin. The percentage of successful retentions was greater for Smallmouth Bass (10.9%) than for Burbot (5%). Reaction probabilities to each prey differed significantly, which resulted in a two‐fold increase in attacks on Mottled Sculpin compared with Round Goby within the same time period. Reaction distances for both predators did not differ regarding prey species, but Smallmouth Bass reacted from farther away than did Burbot (maximum reaction distances of 159 and 98 cm, respectively). Greater success of native predators on native prey has likely caused higher mortality on native prey populations due to greater predator success, while capturing invasive prey decreases the net energy intake.
Seismic damage assessment of a supertall tubed mega frame structure based on a simplified finite element model
Authors: Zhou Zhi , Qian Jiang , Huang Wei , Yao Kun
Published: February 2021

A tubed mega frame structure is composed of tubes located at the perimeter of the structure as mega columns and mega beams. This paper explores the applicability of this structural system to supertall buildings in high seismic intensity areas. First, a refined finite element (FE) model of a 585‐m tall tubed mega frame structure was built in ABAQUS, as well as a mega‐braced frame‐core structure on which the tubed mega frame structure is based. In order to improve the efficiency of nonlinear analyses, beam‐based simplified FE models of the two structures were developed in OpenSees and validated against the refined FE models. Then, incremental dynamic analyses of the tubed mega frame structure were conducted based on its simplified model. The damage of the tubes was quantified by a modified Park–Ang damage model. The analyses indicate that the seismic damage of the tubes in the tubed mega frame structure develops rapidly after yielding, because tubes at the perimeter of the structure suffer severe axial load under high‐intensity earthquakes. It is suggested that the axial load ratio of the tubed mega columns should be controlled to avoid brittle failure in the seismic design of supertall tubed mega frame structures.
Cadmium cytotoxicity and possible mechanisms in human trophoblast HTR‐8/SVneo cells
Authors: Liao Ying , Zheng Hong , Wu Langbo , He Lei , Wang Yu , Ou Yangsong , Yang Hongjun , Peng Shiqin , Chen Fengwang , Wang Xiaoyan , Zhao Jiayuan
Published: February 2021

The accumulation of cadmium (Cd) in the human body through food chain can lead to adverse pregnancy outcomes. In this study, Cd cytotoxicity and its mechanisms in HTR‐8/SVneo cells were investigated. Cd disrupted the cellular submicrostructure and inhibited the cell viability in a time‐ and dose‐dependent manner. The levels of reactive oxygen species, malondialdehyde content, and the activities of glutathione peroxidase (GSH‐Px) and total superoxode dismutase (T‐SOD) were concentration‐dependently increased by Cd. In addition, Cd dose‐dependently inducedcell apoptosis and decreased cell migration and invasion capacities. Finally, Cd significantly upregulated all the genes related to oxidative stress (SOD1, ROS1, and HSPA6), inflammatory response, cell cycle, apoptosis, and migration and invasion. This study will provide insights into the prevention and treatment of pregnancy‐related diseases caused by Cd intoxication.
Design of polymers for siRNA delivery: Recent progress and challenges
Authors: Wang Hui , Zhang Song , Lv Jia , Cheng Yiyun
Published: February 2021

RNA interference with the ability to specifically silence target genes has shown great potential to treat various diseases. The primary challenge for RNA interference is to effectively and selectively deliver genetic materials such as small interfering RNA (siRNA) to targeted tissues and cells in vivo. Numerous efforts have been made to overcome the extracellular and intracellular barriers during siRNA delivery. In this review, we focused on most recent advances in the design of functional polymers to achieve efficient siRNA delivery via addressing the various parameters, including siRNA binding, serum stability, specific targeting, tissue penetration, cellular internalization, endosomal escape, and intracellular siRNA release. The beneficial roles of assembled polymer nanostructures and polymer‐based hybrid nanocomposites in siRNA delivery were also reviewed. Finally, the challenges and perspectives in the future development of polymer‐based siRNA delivery systems will be discussed.
Broiler production challenges in the tropics: A review
Authors: Kpomasse Cocou Claude , Oke Oyegunle Emmanuel , Houndonougbo Frédérick Makpondji , Tona Kokou
Published: February 2021

Under tropical climate, broiler production is encumbered by several constraints which make it difficult for them to attain their genetic potential. The scarcity and high price of poultry feed and veterinary services and the harsh environmental conditions with respect to thermal stress are some of the challenges that hinder optimal growth of the birds. Limited availability of feedstuffs, including crucial feed ingredients like maize and oil seedcakes, is an important challenge to the sector, since feed still represents a major cost of producing broiler chickens. Additionally, the problem of climate change, which has become a global concern, is the main problem in broiler production under hot and humid climate. Under high ambient temperature, feed intake decreases, carbohydrates metabolism and protein synthesis efficiency are disturbed. Lipid utilization is lower and glucose or insulin homeostasis is altered while fat deposition and oxidative stress increases. Several strategies are used to ameliorate the effect of heat stress in poultry. The objective of this review was to summarize the challenge in broiler production under hot and humid climate and different approaches to fight heat stress in poultry.
The Sivers asymmetry in hadronic dijet production
Authors: Kang Zhong-Bo , Lee Kyle , Shao Ding Yu , Terry John
Published: February 2021

Abstract

We study the single spin asymmetry in the back-to-back dijet production in transversely polarized proton-proton collisions. Such an asymmetry is generated by the Sivers functions in the incoming polarized proton. We propose a QCD formalism in terms of the transverse momentum dependent parton distribution functions, which allow us to resum the large logarithms that arise in the perturbative calculations. We make predictions for the Sivers asymmetry of hadronic dijet production at the kinematic region that is relevant to the experiment at the Relativistic Heavy Ion Collider (RHIC). We further compute the spin asymmetries in the selected positive and negative jet charge bins, to separate the contributions from u- and d-quark Sivers functions. We find that both the sign and size of our numerical results are roughly consistent with the preliminary results from the STAR collaboration at the RHIC.
Double parton distributions in the pion from lattice QCD
Authors: Bali Gunnar S. , Castagnini Luca , Diehl Markus , Gaunt Jonathan R. , Gläßle Benjamin , Schäfer Andreas , Zimmermann Christian
Published: February 2021

Abstract

We perform a lattice study of double parton distributions in the pion, using the relationship between their Mellin moments and pion matrix elements of two local currents. A good statistical signal is obtained for almost all relevant Wick contractions. We investigate correlations in the spatial distribution of two partons in the pion, as well as correlations involving the parton polarisation. The patterns we observe depend significantly on the quark mass. We investigate the assumption that double parton distributions approximately factorise into a convolution of single parton distributions.
Gapped Goldstones at the cut-off scale: a non-relativistic EFT
Authors: Cuomo G. , Esposito A. , Gendy E. , Khmelnitsky A. , Monin A. , Rattazzi R.
Published: February 2021

Abstract

At finite density, the spontaneous breakdown of an internal non-Abelian symmetry dictates, along with gapless modes, modes whose gap is fixed by the algebra and proportional to the chemical potential: the gapped Goldstones. Generically the gap of these states is comparable to that of other non-universal excitations or to the energy scale where the dynamics is strongly coupled. This makes it non-straightforward to derive a universal effective field theory (EFT) description realizing all the symmetries. Focusing on the illustrative example of a fully broken SU(2) group, we demonstrate that such an EFT can be constructed by carving out around the Goldstones, gapless and gapped, at small 3-momentum. The rules governing the EFT, where the gapless Goldstones are soft while the gapped ones are slow, are those of standard nonrelativistic EFTs, like for instance nonrelativistic QED. In particular, the EFT Lagrangian formally preserves gapped Goldstone number, and processes where such number is not conserved are described inclusively by allowing for imaginary parts in the Wilson coefficients. Thus, while the symmetry is manifestly realized in the EFT, unitarity is not. We comment on the application of our construction to the study of the large charge sector of conformal field theories with non-Abelian symmetries.
2020 global reassessment of the neutrino oscillation picture
Authors: de Salas P. F. , Forero D. V. , Gariazzo S. , Martínez-Miravé P. , Mena O. , Ternes C. A. , Tórtola M. , Valle J. W. F.
Published: February 2021

Abstract

We present an updated global fit of neutrino oscillation data in the simplest three-neutrino framework. In the present study we include up-to-date analyses from a number of experiments. Concerning the atmospheric and solar sectors, besides the data considered previously, we give updated analyses of IceCube DeepCore and Sudbury Neutrino Observatory data, respectively. We have also included the latest electron antineutrino data collected by the Daya Bay and RENO reactor experiments, and the long-baseline T2K and NOνA measurements, as reported in the Neutrino 2020 conference. All in all, these new analyses result in more accurate measurements of θ13, θ12, $$ \Delta {m}_{21}^2 $$
Δ

m
21
2

and $$ \left|\Delta {m}_{31}^2\right| $$

Δ

m
31
2

. The best fit value for the atmospheric angle θ23 lies in the second octant, but first octant solutions remain allowed at ∼ 2.4σ. Regarding CP violation measurements, the preferred value of δ we obtain is 1.08π (1.58π) for normal (inverted) neutrino mass ordering. The global analysis still prefers normal neutrino mass ordering with 2.5σ statistical significance. This preference is milder than the one found in previous global analyses. These new results should be regarded as robust due to the agreement found between our Bayesian and frequentist approaches. Taking into account only oscillation data, there is a weak/moderate preference for the normal neutrino mass ordering of 2.00σ. While adding neutrinoless double beta decay from the latest Gerda, CUORE and KamLAND-Zen results barely modifies this picture, cosmological measurements raise the preference to 2.68σ within a conservative approach. A more aggressive data set combination of cosmological observations leads to a similar preference for normal with respect to inverted mass ordering, namely 2.70σ. This very same cosmological data set provides 2σ upper limits on the total neutrino mass corresponding to Σmν< 0.12 (0.15) eV in the normal (inverted) neutrino mass ordering scenario. The bounds on the neutrino mixing parameters and masses presented in this up-to-date global fit analysis include all currently available neutrino physics inputs.
Islands in de Sitter space
Authors: Balasubramanian Vijay , Kar Arjun , Ugajin Tomonori
Published: February 2021

Abstract

We consider black holes in 2d de Sitter JT gravity coupled to a CFT, and entangled with matter in a disjoint non-gravitating universe. Tracing out the entangling matter leaves the CFT in a density matrix whose stress tensor backreacts on the de Sitter geometry, lengthening the wormhole behind the black hole horizon. Naively, the entropy of the entangling matter increases without bound as the strength of the entanglement increases, but the monogamy property predicts that this growth must level off. We compute the entropy via the replica trick, including wormholes between the replica copies of the de Sitter geometry, and find a competition between conventional field theory entanglement entropy and the surface area of extremal “islands” in the de Sitter geometry. The black hole and cosmological horizons both play a role in generating such islands in the backreacted geometry, and have the effect of stabilizing the entropy growth as required by monogamy. We first show this in a scenario in which the de Sitter spatial section has been decompactified to an interval. Then we consider the compact geometry, and argue for a novel interpretation of the island formula in the context of closed universes that recovers the Page curve. Finally, we comment on the application of our construction to the cosmological horizon in empty de Sitter space.
Is N = 2 Large?
Authors: Kitano Ryuichiro , Yamada Norikazu , Yamazaki Masahito
Published: February 2021

Abstract

We study θ dependence of the vacuum energy for the 4d SU(2) pure Yang-Mills theory by lattice numerical simulations. The response of topological excitations to the smearing procedure is investigated in detail, in order to extract topological information from smeared gauge configurations. We determine the first two coefficients in the θ expansion of the vacuum energy, the topological susceptibility χ and the first dimensionless coefficient b2, in the continuum limit. We find consistency of the SU(2) results with the large N scaling. By analytic continuing the number of colors, N , to non-integer values, we infer the phase diagram of the vacuum structure of SU(N) gauge theory as a function of N and θ. Based on the numerical results, we provide quantitative evidence that 4d SU(2) Yang-Mills theory at θ = π is gapped with spontaneous breaking of the CP symmetry.
The ICON Trauma Study: the impact of the COVID-19 lockdown on major trauma workload in the UK
Authors: Adiamah Alfred , Thompson Amari , Lewis-Lloyd Christopher , Dickson Edward , Blackburn Lauren , Moody Nick , Gida Sunil , La Valle Angelo , Reilly John-Joe , Saunders John , Brooks Adam ,   The ICON Trauma Study Group, Adiamah Alfred , Anis Fady , Blackburn Lauren , Brewer Hilary , Brooks Adam , Brailsford Rachel , Boardman Shannon , Dahaley Amanjeet , Dickson Edward , Draper Zoe , Freij Ramzi , Gaskin Wendy , Gida Sunil , Hutchinson Lauren , Jackman Jamaall , Kapeleris Audrey , Koh Amanda , Lamb Christopher , Lewis-Lloyd Christopher , La Valle Angelo , Lee Rachel , McSweeny Shane , Nassif Yasar , Navarro Alex , O’Connor Rory , O’Sullivan Ciara , Oyende Olamide , Reilly John-Joe , Sanderson Sharon , Saunders John , Thompson Amari , Theophilidou Elena , Walsh Sandeep , Winter Robert
Published: February 2021

Background

The global pandemic caused by SARS-CoV-2 has impacted population health and care delivery worldwide. As information emerges regarding the impact of “lockdown measures” and changes to clinical practice worldwide; there is no comparative information emerging from the United Kingdom with regard to major trauma.

Methods

This observational study from a UK Major Trauma Centre matched a cohort of patients admitted during a 10-week period of the SARS-CoV-2-pandemic (09/03/2020–18/05/2020) to a historical cohort of patients admitted during a similar time period in 2019 (11/03/2019–20/05/2019). Differences in demographics, Clinical Frailty Scale, SARS-CoV-2 status, mechanism of injury and injury severity were compared using Fisher’s exact and Chi-squared tests. Univariable and multivariable logistic regression analyses examined the associated factors that predicted 30-days mortality.

Results

A total of 642 patients were included, with 405 in the 2019 and 237 in the 2020 cohorts, respectively. 4/237(1.69%) of patients in the 2020 cohort tested positive for SARS-CoV-2. There was a 41.5% decrease in the number of trauma admissions in 2020. This cohort was older (median 46 vs 40 years), had more comorbidities and were frail (p < 0.0015). There was a significant difference in mechanism of injury with a decrease in vehicle related trauma, but an increase in falls. There was a twofold increased risk of mortality in the 2020 cohort which in adjusted multivariable models, was explained by injury severity and frailty. A positive SARS-CoV-2 status was not significantly associated with increased mortality when adjusted for other variables.

Conclusion

Patients admitted during the COVID-19 pandemic were older, frailer, more co-morbid and had an associated increased risk of mortality.
Risikokommunikation bei der Eindämmung der COVID-19-Pandemie: Herausforderungen und Erfolg versprechende Ansätze
Authors: Loss Julika , Boklage Evgeniya , Jordan Susanne , Jenny Mirjam A. , Weishaar Heide , El Bcheraoui Charbel
Published: February 2021

Risikokommunikation spielt eine zentrale Rolle in Public-Health-Notlagen: Sie muss informierte Entscheidungen ermöglichen, schützendes bzw. lebenserhaltendes Verhalten fördern und das Vertrauen in öffentliche Institutionen bewahren. Zudem müssen Unsicherheiten über wissenschaftliche Erkenntnisse transparent benannt werden, irrationale Ängste und Gerüchte entkräftet werden. Risikokommunikation sollte die Bevölkerung partizipativ einbeziehen. Ihre Risikowahrnehmung und -kompetenz müssen kontinuierlich erfasst werden. In der aktuellen Pandemie der Coronavirus-Krankheit 2019 (COVID-19) ergeben sich spezifische Herausforderungen für die Risikokommunikation.

Der Wissensstand zu vielen wichtigen Aspekten, die COVID-19 betreffen, war und ist oftmals unsicher oder vorläufig, z. B. zu Übertragung, Symptomen, Langzeitfolgen und Immunität. Die Kommunikation ist durch wissenschaftliche Sprache sowie eine Vielzahl von Kennzahlen und Statistiken geprägt, was die Verständlichkeit erschweren kann. Neben offiziellen Mitteilungen und Einschätzungen von Expertinnen und Experten wird über COVID-19 in großem Umfang in sozialen Medien kommuniziert, dabei werden auch Fehlinformationen und Spekulationen verbreitet; diese „Infodemie“ erschwert die Risikokommunikation.

Nationale wie internationale Forschungsprojekte sollen helfen, die Risikokommunikation zu COVID-19 zielgruppenspezifischer und effektiver zu machen. Dazu gehören u. a. explorative Studien zum Umgang mit COVID-19-bezogenen Informationen, das COVID-19 Snapshot Monitoring (COSMO), ein regelmäßig durchgeführtes Onlinesurvey zu Risikowahrnehmung und Schutzverhalten sowie eine interdisziplinäre qualitative Studie, die die Konzeption, Umsetzung und Wirksamkeit von Risikokommunikationsstrategien vergleichend in 4 Ländern untersucht.
Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study
Authors: Biessels Geert Jan , Verhagen Chloë , Janssen Jolien , van den Berg Esther , Wallenstein Gudrun , Zinman Bernard , Espeland Mark A. , Johansen Odd Erik
Published: February 2021

Aims/hypothesis

Type 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes.

Methods

The CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA1c 48–69 mmol/mol (6.5–8.5%) receiving standard care, excluding insulin therapy. Participants were randomised 1:1 using an interactive telephone- and web-based system and treatment assignment was determined by a computer-generated random sequence with stratification by center. The primary cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression-based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning, in participants with a baseline MMSE score ≥24. Prespecified additional analyses included effects on ACD at week 160, in subgroups (sex, age, race, ethnicity, depressive symptoms, cardiovascular risk, duration of type 2 diabetes, albuminuria), and absolute changes in cognitive performance. Participants, caregivers, and people involved in measurements, examinations or adjudication, were all masked to treatment assignment.

Results

Of 6033 participants recruited from hospital and primary care sites, 3163 (38.0% female, mean age/diabetes duration 64/7.6 years, MMSE score 28.5, HbA1c 54 mmol/mol [7.1%]) represent the CAROLINA-COGNITION cohort. Over median 6.1 years, ACD occurred in 27.8% (449/1618, linagliptin) vs 27.6% (426/1545, glimepiride), OR 1.01 (95% CI 0.86, 1.18). Also, no differences in ACD were observed at week 160 (OR 1.07 [0.91, 1.25]), between treatments across subgroups, or for absolute cognitive changes.

Conclusions/interpretation

In a large, international outcome trial in people with relatively early type 2 diabetes at elevated cardiovascular risk, no difference in risk for ACD was observed between linagliptin and glimepiride over 6.1 years.

Funding

This study was sponsored by Boehringer Ingelheim.

Trial registration

ClinicalTrials.gov NCT01243424.

Graphical abstract
Imprecise inference based on the log-rank test for accelerated life testing
Authors: Coolen Frank P. A. , Ahmadini Abdullah A. H. , Coolen-Maturi Tahani
Published: February 2021

This paper presents an imprecise predictive inference method for accelerated life testing. The method is largely nonparametric, with a basic parametric function to link different stress levels. The log-rank test is used to provide imprecision for the link function parameter, which in turn provides robustness in the resulting lower and upper survival functions for a future observation at the normal stress level. An application using data from the literature is presented, and simulations show the performance and robustness of the method. In case of model misspecification, robustness may be achieved at the price of large imprecision, which would emphasize the need for more data or further model assumptions.
The volunteer’s dilemma in finite populations
Authors: Konrad Kai A. , Morath Florian
Published: February 2021

We study the long-run stochastic stability properties of volunteering strategies in finite populations. We allow for mixed strategies, characterized by the probability that a player may not volunteer. A pairwise comparison of evolutionary strategies shows that the strategy with a lower probability of volunteering is advantaged. However, in the long run there are also populations of volunteering types. Monomorphisms with the more volunteering types are more frequent if the populations have fewer members, and if the benefits from volunteering are larger. Such monomorphisms with volunteering cease to exist if the population becomes infinitely large. In contrast, the disadvantage of volunteering disappears if the ratio of individual benefits and costs of volunteering becomes infinitely large.
Involuntary reflexive pelvic floor muscle training in addition to standard training versus standard training alone for women with stress urinary incontinence: a randomized controlled trial
Authors: Luginbuehl Helena , Lehmann Corinne , Koenig Irene , Kuhn Annette , Buergin Reto , Radlinger Lorenz
Published: February 2021

Introduction and hypothesis

Although involuntary reflexive pelvic floor muscle contractions seem crucial during stress urinary incontinence-provoking situations, hitherto existing guidelines feature voluntary pelvic floor muscle training only. Two pelvic floor muscle protocols were compared regarding their effect on stress urinary incontinence in women: one focusing on standard physiotherapy with voluntary pelvic floor muscle training, the other additionally including involuntary reflexive pelvic floor muscle training.

Methods

This study was designed as a triple-blind prospective randomized controlled trial with women suffering from stress urinary incontinence with two physiotherapy intervention groups (control group: standard physiotherapy, n = 48, experimental group: standard physiotherapy plus involuntary reflexive pelvic floor muscle training triggered by whole-body movements such as jumps n = 48). Both interventions lasted 16 weeks (9 personal physiotherapy consultations and 78 home training sessions). Group differences and development over time were analyzed concerning the primary outcome International Consultation on Incontinence Modular Questionnaire Urinary Incontinence short form (ICIQ-UIsf) by mixed effect regression models.

Results

The ICIQ-UIsf score decreased significantly over time for both groups by about 3 points from about 10 to about 7 points with no group differences at any point in time.

Discussion

This trial did not find any additional benefit for stress urinary incontinence by adding involuntary reflexive pelvic floor muscle training to standard training. Both training protocols showed similar clinically relevant improvements; however, there was still moderate incontinence after interventions. Future studies should test and apply pelvic floor muscle function-oriented training methods for pelvic floor muscle hypertrophy, intramuscular coordination, and power, which are more in line with conventional skeletal muscle training, i.e., performed with higher intensities and workout.
Arithmetic hyperbolicity: automorphisms and persistence
Authors: Javanpeykar Ariyan
Published: February 2021

We show that if the automorphism group of a projective variety is torsion, then it is finite. Motivated by Lang’s conjecture on rational points of hyperbolic varieties, we use this to prove that a projective variety with only finitely many rational points has only finitely many automorphisms. Moreover, we investigate to what extent finiteness of S-integral points on a variety over a number field persists over finitely generated fields. To this end, we introduce the class of mildly bounded varieties and prove a general criterion for proving this persistence.
Eigenvalue bounds for non-selfadjoint Dirac operators
Authors: D’Ancona Piero , Fanelli Luca , Schiavone Nico Michele
Published: February 2021

We prove that the eigenvalues of the n-dimensional massive Dirac operator $${\mathscr {D}}_0 + V$$

D
0

+
V

, $$n\ge 2$$

n
≥
2

, perturbed by a potential V, possibly non-Hermitian, are contained in the union of two disjoint disks of the complex plane, provided V is sufficiently small with respect to the mixed norms $$L^1_{x_j} L^\infty _{{\widehat{x}}_j}$$

L

x
j

1

L

x
^

j

∞

, for $$j\in \{1,\dots ,n\}$$

j
∈
{
1
,
⋯
,
n
}

. In the massless case, we prove instead that the discrete spectrum is empty under the same smallness assumption on V, and in particular the spectrum coincides with the spectrum of the unperturbed operator: $$\sigma ({\mathscr {D}}_0+V)=\sigma ({\mathscr {D}}_0)={\mathbb {R}}$$

σ

(

D
0

+
V
)

=
σ

(

D
0

)

=
R

. The main tools used are an abstract version of the Birman–Schwinger principle, which allows in particular to control embedded eigenvalues, and suitable resolvent estimates for the Schrödinger operator.
Effect of high levels of CO2 and O2 on membrane fatty acid profile and membrane physiology of meat spoilage bacteria
Authors: Kolbeck Sandra , Kienberger Hermine , Kleigrewe Karin , Hilgarth Maik , Vogel Rudi F.
Published: February 2021

The membrane is the major protective barrier separating the cell from the environment and is thus important for bacteria to survive environmental stress. This study investigates changes in membrane lipid compositions and membrane physiology of meat spoiling bacteria in response to high CO2 (30%) and O2 (70%) concentrations, as commonly used for modified atmosphere packaging of meat. Therefore, the fatty acid profile as well as membrane fluidity, permeability and cell surface were determined and correlated to the genomic settings of five meat spoiling bacteria Brochothrix (B.) thermosphacta, Carnobacterium (C.) divergens, C. maltaromaticum, Leuconostoc (L.) gelidum subsp. gelidum and L. gelidum subsp. gasicomitatum cultivated under different gas atmospheres. We identified different genomic potentials for fatty acid adaptations, which were in accordance with actual measured changes in the fatty acid composition for each species in response to CO2 and/or O2, e.g., an increase in saturated, iso and cyclopropane fatty acids. Even though fatty acid changes were species-specific, the general physiological responses were similar, comprising a decreased membrane permeability and fluidity. Thus, we concluded that meat spoiling bacteria facilitate a change in membrane fatty acids upon exposure to O2 and CO2, what leads to alteration of membrane fluidity and permeability. The observed adaptations might contribute to the resistance of meat spoilers against detrimental effects of the gases O2 and CO2 and thus help to explain their ability to grow under different modified atmospheres. Furthermore, this study provides fundamental knowledge regarding the impact of fatty acid changes on important membrane properties of bacteria.
Effects of Bisphosphonate Treatment on Circulating Lipid and Glucose Levels in Patients with Metabolic Bone Disorders
Authors: Iannuzzo Gabriella , De Filippo Gianpaolo , Merlotti Daniela , Abate Veronica , Buonaiuto Alessio , Evangelista Marco , Gentile Marco , Giaquinto Alfonso , Picchioni Tommaso , Di Minno Matteo Nicola Dario , Strazzullo Pasquale , Gennari Luigi , Rendina Domenico
Published: February 2021

Bisphosphonates are the first-choice treatment of osteoporosis and Paget’s disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget’s disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations.
The impact of turbidity on foraging and risk taking in the invasive Nile tilapia (Oreochromis niloticus) and a threatened native cichlid (Oreochromis amphimelas)
Authors: Wing Jonathan D. B. , Champneys Toby S. , Ioannou Christos C.
Published: February 2021

Anthropogenic activity can increase water turbidity, changing fish behaviour by reducing visibility. The spread of invasive species is also facilitated by human activity, further increasing the pressure on native species. In two experiments, we measured the foraging efficiency, risk perception and inter-individual consistency of risk-taking (personality variation in boldness) of an invasive species, the Nile tilapia (Oreochromis niloticus), and a threatened tilapia, the Manyara tilapia (Oreochromis amphimelas), in clear and turbid water. In experiment one, O. niloticus was faster to initiate feeding, encountered more food items and consumed more than O. amphimelas. The latency to start foraging by O. niloticus decreased in turbid water. Turbidity did not affect the latency to start foraging in O. amphimelas but the number of food items they encountered was highest at the intermediate turbidity. There was however no significant effect of turbidity in either species on the total food consumed. In contrast to this foraging context, in experiment two with a refuge and no food available, risk taking behaviour was similar in both species and they both responded with similarly reduced risk taking in turbid water. Evidence of personality variation was weak, being observed only in O. amphimelas when first leaving the shelter in turbid water. Overall, species differences were greater in the foraging context but turbidity was more important in the risk-taking context. O. amphimelas is more sensitive to turbidity during foraging, and O. niloticus is likely to have a competitive advantage in foraging situations, especially in degraded turbid habitats.

Significance statement

Under human-induced environmental change, native species are often exposed to multiple stressors. Here, we tested the responses of two cichlid fish to increasing turbidity, the Nile tilapia (Oreochromis niloticus), which is invasive throughout the tropics, and the Manyara tilapia (Oreochromis amphimelas), a threatened species, indigenous to Tanzania. We found that turbidity was beneficial to the foraging of O. niloticus, which in both clear and turbid water consumed and encountered more food than O. amphimelas. In contrast, without food present, both species displayed similar responses of increased risk perception in turbid water with little evidence of personality variation between individuals in either species. Our results suggest that invasive species tolerant of degraded habitats may outcompete less well-adapted native species for food.
A proposal for a new classification of coracobrachialis muscle morphology
Authors: Szewczyk Bartłomiej , Polguj Michał , Paulsen Friedrich , Podgórski Michał , Duparc Fabrice , Karauda Piotr , Olewnik Łukasz
Published: February 2021

Introduction

The coracobrachialis muscle (CRM) originates from the apex of the coracoid process, in common with the short head of the biceps brachii muscle, and from the intermuscular septum. It inserts to the medial part of the humerus between the attachment of the medial head of the triceps brachii and the brachial muscle. Both the proximal and distal attachments of the CRM, as well as its relationship with the musculocutaneus nerve, demonstrate morphological variability.

Material and methods

One hundred and one upper limbs (52 left, and 49 right) fixed in 10% formalin solution were examined.

Results

Three main types, with subtypes, were identified. The most common was Type I (49.5), characterized by a single muscle belly with a classical origin from the coracoid process, medially and posteriorly to the tendon of the biceps brachii. Type II (42.6%), characterized by two heads, was divided into two subtypes (A-B) depending on its origin: Type IIA, where one head originated from the coracoid process posteriorly to the tendon of the biceps brachii and the second head from the short head of the biceps brachii, and Type IIB, in which both heads originated from the coracoid process; however, the superficial head fused with the insertion of a short head of the biceps brachii, while the deep head was directly originating. Finally, Type III (7.9%) was characterized by three heads: two originated from the coracoid process (superficial and deep), and the third from a short head of the biceps brachii. Two types of insertion and two types of musculocutaneous nerve (MCN) relative to CRM could be distinguished.

Conclusion

An adapted classification is needed for all clinicians working in this area, as well as for anatomists. The CRM demonstrates morphological variability in both its proximal and distal attachments, as well as the variable course of the MCN relative to the CRM.

What is known about this subject "and" What this study adds to existing knowledge

Not much is known about the variability of coracobrachialis muscle. The present paper introduces a completely new classification, both clinical and anatomical.
Auswirkungen der Coronapandemie auf soziale Netzwerke in Risikofamilien
Authors: Knabe André , Kölch Michael , Spitzer Carsten , Reis Olaf
Published: February 2021

Hintergrund

Die Maßnahmen zur Reduktion des Infektionsgeschehens im Rahmen der Coronapandemie brachten insbesondere für Familien mit schulpflichtigen Kindern erhebliche Einschränkungen mit sich. Besonders betroffen sind Risikofamilien, die bereits vor der Pandemie mit psychischen Störungen, Armut oder beengtem Wohnraum konfrontiert waren.

Fragestellung

Wie stellen sich Zusammensetzung und Dynamik der sozialen Netzwerke von Risikofamilien während des Lockdowns dar?

Material und Methode

„Mixed-methods“-Analyse auf Basis von 19 qualitativen Leitfadeninterviews und 18 standardisiert erhobenen egozentrierten Netzwerken mit 224 von den Befragten („ego“) genannten Personen („alter“).

Ergebnisse

Netzwerke werden durch die Krise geschwächt. Gleichzeitig sind sie wichtigste Ressource der Bewältigung. Unterstützung fehlt v. a. bei der Sorge um die psychisch erkrankten Kinder. Wichtigste Quellen von Unterstützung sind die erweiterte Familie und institutionelle Einrichtungen. Letztere waren in der Krise oft nur noch eingeschränkt oder gar nicht mehr zu erreichen. Im Idealfall sind die verbliebenen Beziehungen stark genug, um die Situation zu überstehen. Im schlimmsten Fall werden die Kinder nicht nur aus institutionellen Strukturen entlassen (Kita, Schule, medizinische und therapeutische Hilfen), sondern verschwinden ganz und gar aus der institutionellen und gesellschaftlichen Obhut. Ihr Wohl hängt dann allein von den Kompetenzen ihrer Eltern ab.

Schlussfolgerung

In Zeiten von Kontaktbeschränkungen benötigen Risikofamilien besondere Aufmerksamkeit. Es genügt nicht, darauf zu warten, dass sie von sich aus um Hilfe oder eine Notbetreuung für die Kinder bitten. Institutionen sollten proaktiv praktische und informationelle Unterstützung anbieten.
Forecast skill of the Indian monsoon and its onset in the ECMWF seasonal forecasting system 5 (SEAS5)
Authors: Chevuturi Amulya , Turner Andrew G. , Johnson Stephanie , Weisheimer Antje , Shonk Jonathan K. P. , Stockdale Timothy N. , Senan Retish
Published: February 2021

Accurate forecasting of variations in Indian monsoon precipitation and progression on seasonal time scales remains a challenge for prediction centres. We examine prediction skill for the seasonal-mean Indian summer monsoon and its onset in the European Centre for Medium-Range Weather Forecasts (ECMWF) seasonal forecasting system 5 (SEAS5). We analyse summer hindcasts initialised on 1st of May, with 51 ensemble members, for the 36-year period of 1981–2016. We evaluate the hindcasts against the Global Precipitation Climatology Project (GPCP) precipitation observations and the ECMWF reanalysis 5 (ERA5). The model has significant skill at forecasting dynamical features of the large-scale monsoon and local-scale monsoon onset tercile category one month in advance. SEAS5 shows higher skill for monsoon features calculated using large-scale indices compared to those at smaller scales. Our results also highlight possible model deficiencies in forecasting the all India monsoon rainfall.