bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of drug formulations on kinetics and toxicity in a preclinical model of paclitaxel‐induced neuropathy
Authors: Klein Ines , Wiesen Martin H. J. , Albert Virginia , Bobylev Ilja , Joshi Abhijeet R. , Müller Carsten , Lehmann Helmar C.
Published: March 2021

Peripheral neuropathy is a common side effect of paclitaxel. Clinical studies suggest that different paclitaxel formulations influence the severity and time course of paclitaxel‐induced peripheral neuropathy. We compared two paclitaxel formulations, nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) and Cremophor EL paclitaxel (CreEL‐paclitaxel), for their toxicity, distribution, and clearance in the peripheral nervous system. Neuronal F11 cells were used to detect changes in morphology, cell nuclei size, and cell viability after nab‐ or CreEL‐paclitaxel treatment via MTT Assay and immunohistochemistry. C57BL/6 mice were treated with 50 mg/kg of nab‐paclitaxel or CreEL‐paclitaxel. Paclitaxel levels in serum, liver, dorsal root ganglia (DRG), and sciatic nerve (SCN) were measured by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Accumulation of paclitaxel in DRG neurons and SCN was visualized by immunostainings. Neurotoxicity was evaluated after a 4‐week treatment regime with nab‐ or CreEL‐paclitaxel by nerve morphology, behavioral, and functional assays. In vitro cell nuclei size and morphology were similar between the two treatment groups. Viability was increased in neurons exposed to nab‐paclitaxel compared to CreEL‐paclitaxel. In vivo paclitaxel mostly accumulated in DRG. SCN displayed lower paclitaxel uptake. The two paclitaxel formulations mainly accumulated in neurofilament 200‐positive large‐caliber neurons and less in Isolectin B4‐, or calcitonin gene‐related peptide‐positive small‐caliber neurons. Sensory nerve conduction studies demonstrated increased sensory latencies after 11 days in nab‐paclitaxel treated animals, while an increase occurred after 22 days in CreEL‐paclitaxel treated animals. Behavioral testing did not reveal significant differences between the different groups. Skin denervation, axon count, myelin thickness, and F4/80‐positive cell accumulation were comparable between the two treatment groups. Our findings indicate that different drug formulations impact the severity of neuropathy induced by paclitaxel via different tissue uptake. Neurotoxicity was comparable between the two paclitaxel formulations.
Range Extension of Mesophotic Kelps (Ochrophyta: Laminariales and Tilopteridales) in the Central North Atlantic: Opportunities for Marine Forest Research and Conservation
Authors: Tempera Fernando , Milla‐Figueras David , Sinde‐Mano Ana Luísa , Atchoi Elizabeth , Afonso Pedro
Published: March 2021

Kelp was first recorded for the remote warm‐temperate Azores archipelago (central North Atlantic) in 1971, when a few Laminaria specimens were collected on the Formigas Bank at depths beyond conventional SCUBA diving reach. A shortage of technical means and projects targeting mesophotic environments has since kept this offshore marine protected area as the single known kelp occurrence site. Here, we present new kelp records collected on previously unexplored mesophotic reefs using remote imaging systems, open‐ and closed‐circuit SCUBA diving, and fisheries bycatch information. The new data extend the known distribution range of kelp in the Azores 350 km to the west and 25 km to the southwest, henceforth including several island shelves in the eastern and central Azores. In addition to the previously recorded Laminaria ochroleuca, kelp specimens with a morphology akin to Phyllariopsis brevipes subsp. brevipes are also reported. For the first time, seabed imagery is used to document the depth‐wise diversity of the Azores kelp beds and their associated biota. Our findings emphasize the poor knowledge that persists in regard to Macaronesia’s mesophotic environments located beyond conventional SCUBA diving limits. The new on‐shelf kelp occurrences add conservation value to coastal areas and should facilitate island‐based research. However, their greater proximity to land‐based impacts and exposure to climate change also raise management needs.
Testing small‐scale ecological gradients and intraspecific differentiation for hundreds of kelp forest species using haplotypes from metabarcoding
Authors: Shum Peter , Palumbi Stephen R.
Published: March 2021

DNA metabarcoding has been increasingly used to detail distributions of hundreds of species. Most analyses focus on creating molecular operational taxonomic units (MOTUs) from complex mixtures of DNA sequences, but much less common is use of the sequence diversity within these MOTUs. Here we use the diversity of COI haplotypes within MOTUs from a California kelp forest to infer patterns of population abundance, dispersal and population history from 527 species of animals and algae from 106 samples of benthic habitats in Monterey Bay. Using haplotypes as a unit we show fine‐grained differences of abundance across locations for 15 species, and marked aggregation from sample to sample for most of the common species of plants and animals. Previous analyses could not distinguish these patterns from artefacts of amplification or sequence bias. Our haplotype data also reveal strong population genetic differentiation over small spatial scales for 48 species of red algae, sponges and Bryozoa. Last, phylogenetic analysis of mismatch frequencies among haplotypes show a wide variety of demographic histories from recent expansions to long, stable population sizes. These analyses show that abundant, small‐bodied marine species that are often overlooked in ecological surveys can have strikingly different patterns of ecological and genetic structure leading to population, ecological and perhaps adaptive differences between habitats. MOTU diversity data from the same sequencing efforts that generate species‐level analyses can greatly increase the scope and value of metabarcoding studies.
The perceived unity of time
Authors: Viera Gerardo
Published: March 2021

While we perceive events in our environment through multiple sensory systems, we nevertheless perceive all of these events as occupying a single unified timeline. Time, as we perceive it, is unified. I argue that existing accounts of the perceived unity of time fail. Instead, the perceived unity of time must be constructed by integrating our initially fragmented timekeeping capacities. However, existing accounts of multimodal integration do not tell us how this might occur. Something new is needed. I finish the paper by articulating the hurdles that must be overcome to provide an account of the perceived unity of time.
Collaboration as Process: The Making of a Partnership to Serve At‐Risk Youths of Haitian Descent
Authors: Marcelin Louis Herns , Dembo Richard , Cela Toni , Burgos Catherimarty , Copeland Morris , Page Bryan
Published: March 2021

The increasingly intractable nature of many social problems has given rise to cross‐institutional and interdisciplinary collaborations in order to respond to social problems that no single entity can resolve on its own. One value of anthropology lies in its capacity to provide culturally tailored strategies for successful collaboration between different stakeholders in communities, across disciplinary fields, among public policymakers and practitioners. In this article, we revisit the emergence of a collaborative initiative to support at‐risk youths of Haitian descent and their families. This work was undertaken by university researchers, juvenile justice professionals in Miami‐Dade County, and community‐based practitioners. Guided by a holistic anthropological perspective and a multidimensional approach to collaboration, we provide a processual analysis of almost two decades of opportunities and challenges posed by our collaboration and illuminate the importance of collaboration in identifying evidence‐based solutions to social problems. While not all collaborative teams experience the same processes or operate within the same sociocultural contexts, we argue that there are some fundamental principles to establishing effective collaboration: a shared common goal, shared objectives, and time.
Prediction of levobupivacaine concentrations in neonates and infants following neuraxial rescue blocks
Authors: Frawley Geoff , Cortinez Luis Ignacio , Anderson Brian J.
Published: March 2021

Aim

Pharmacokinetic simulation was used to characterize levobupivacaine disposition after regional anesthetic rescue for failed spinal anesthesia in neonates and infants.

Methods

Population pharmacokinetics of levobupivacaine were estimated after spinal blockade in a cohort of neonates and infants (n = 25, postnatal age 5–18 weeks, gestation 21–41 weeks, weight 2.4–6 kg). Total levobupivacaine concentrations were assayed 3–4 times in the first hour after spinal levobupivacaine 1 mg kg−1 administration. Parameters were estimated using nonlinear mixed‐effects models and supported by priors. Covariates included postnatal age and total body weight. Parameter estimates were used to simulate total levobupivacaine concentrations after a primary spinal levobupivacaine 1 mg kg−1 with rescue caudal levobupivacaine 1.5–2.5 mg kg−1.

Results

A one‐compartment model with a mature clearance 21.5 L h−1 70 kg−1 (CV 47.3%) and central volume 189 L 70 kg−1 (CV 37%) adequately described time‐concentration profiles. Clearance maturation was described using a maturation half‐time of 11.5 weeks postnatal age. The absorption half‐time for spinal levobupivacaine was 2.6 min (CV 56.8%). The upper (97.5% prediction) for peak concentrations after rescue caudal levobupivacaine were 1.5 mg kg−1, 2 mg kg−1, and 2.5 mg kg−1 was 2.05 mg L−1, 2.5 mg L−1, and 2.9 mg L−1 respectively.

Conclusion

Total bupivacaine concentrations greater than 2.5 mg L−1 are associated with neurotoxicity in adults. Predicted concentrations after either a repeat spinal or a caudal rescue dose of levobupivacaine 1.5 mg kg−1 1 h after spinal levobupivacaine administration are below the neurotoxic concentration threshold.
A kindergarten‐based, family‐involved intervention to improve children’s hand hygiene behavior: A cluster‐randomized controlled trial
Authors: Zhang Lifeng , Qin Xiuqun , Zeng Jixiao , Feng Yongshen , Zhang Ningning , Tan Yuqin , Chen Jielin , Chen Shiyin
Published: March 2021

Objective

The present study determined the feasibility and initial efficacy of a kindergarten‐based, family‐involved intervention in improving children's hand hygiene (HH) behaviors.

Design

A cluster‐randomized controlled trial was performed, with a cluster defined as a kindergarten class.

Sample

Participants were recruited from 20 classes in six kindergartens. A total of 289 children and their families were enrolled in the intervention group, and 293 children and their families were enrolled in the control group.

Measurements

HH behavior and a related knowledge survey, as well as data on absences due to infection, were collected.

Intervention

An 8‐week training session on HH for children and an education program combining a seminar and WeChat groups for parents were provided to participants in the intervention group.

Results

Two HH behaviors of children, namely, HH after playing outside and 7‐stage HH compliance, were significantly different between the two groups after the intervention. The two HH behaviors and knowledge of infections of parents/legal guardians in the intervention group were better than those in the control group after the intervention. The number of absences due to infections in children was lower in the intervention group than in the control group.

Conclusions

Kindergarten‐based, family‐involved interventions effectively improved the HH behavior of kindergarten children and decreased absences due to infections.
A pilot study investigating the social contact patterns of Korean elderly
Authors: Oh Hyang Soon , Jeong Sun Young , Yang Youngran
Published: March 2021

Objectives

This pilot study describes the characteristics of social contact patterns of the elderly, a group at high‐risk for contracting infections.

Design

A cross‐sectional design was used.

Sample

Participants included 30 volunteers aged 65 years or older.

Measurements

Records of a contact diary were maintained for a period of 24‐hr.

Results

Thirty participants recorded 340 contacts within the 24 hr period, with a mean of 11.3 people daily. Physical encounters accounted for 50.9% of contacts. Participants with an occupation had significantly higher contacts than those without (p=.013). Contact type differed by location and duration (p<.001). Contact locations included: home (11.5%), work (2.4%), elderly welfare facilities (32.9%), transport (1.2%), and other places (52.1%). Contact duration (p < .001) and frequency (p < .001) differed by location. Contact duration differed by frequency (p < .001).

Conclusions

The elderly participate in frequent physical contact that increases their risk of infection, especially among those with an occupation in comparison to those without an occupation. Infection control nursing should focus on providing education to reduce the risk of infections during contact events. Social distancing should be applied to limited periods of infection transmission risk.
Advancement in our understanding of immune response againstEncephalitozooninfection
Authors: Aseeja Praisy , Shaikh Yasmin , Bajpai Anamika , Sirsikar Prachitee , Kalra Sonali K.
Published: March 2021

Microsporidia are a group of obligate, intracellular, spore‐forming eukaryotic pathogens, which predominantly infects immunocompromised individuals worldwide.Encephalitozoonspp. is one of the most prevalent microsporidia known to infect humans. Host immune system plays a major role in combating pathogens includingEncephalitozoonspp. infecting humans. Both innate and adaptive arms of host immune system work together in combatingEncephalitozooninfection. Researchers are conducting studies to elucidate the role of both arms of immune system againstEncephalitozooninfection. In addition to cell‐mediated adaptive immunity, role of innate immunity is also being highlighted in clearance ofEncephalitozoonspp. from host body. Therefore, the current review will give a clear and consolidated update on the role of innate as well as adaptive immunity in protection againstEncephalitozoonspp.
The novel allele, HLA‐A*32:148, identified by next generation sequencing in a Saudi individual
Authors: AlZahrani Saber , Awaji Mohammad , AlAbduladheem Dalal , Alkebasi Shaima , Al Attas Rabab Ali
Published: March 2021

A single nucleotide substitution in exon 4 of HLA‐A*32:01:01:01 results in novel HLA‐A*32:148 allele.
Interreligious studies and personal changemaking pedagogy for leadership and the common good: The My Story assignment
Authors: Gustafson Hans Stefan
Published: March 2021

This article sketches the scaffolded three‐phase “My Story” assignment, which unfolds over the course of a semester, is embedded in the context of local lived interreligious encounter, and aims at developing interfaith leadership and interreligious wherewithal. The context (large urban Catholic university), purpose (student learning outcomes centered on personal changemaking, self‐knowledge, and leadership), description (concrete nuts and bolts of the assignment's procedure), and efficacy (results of piloting the assignment) of the assignment are discussed.
Studies in Three-Dimensional Photoelasticity: Stresses in Bent Circular Shafts With Transverse Holes—Correlation With Results From Fatigue and Strain Measurements
Authors: Frocht M. M.
Published: March 2021

Bent circular shafts with holes in the plane of bending are of frequent occurrence in modern machines. They often form a part of the lubricating system as, for example, in the crankshafts of aircraft engines. Considerable work has been done to determine the maximum stresses and the factors of stress concentration in such shafts. The author presents a simple method of calculating such stresses for transverse holes in pure bending. Experimental photoelastic evidence that led to this method is given. A comparison of the stress-concentration factors obtained by it is made with the published results from fatigue tests and strain measurements from large steel shafts, which were performed a number of years ago at the Westinghouse Research Laboratories.
The Stresses in Cemented Joints
Authors: Goland M. , Reissner E.
Published: March 2021

The determination of the stresses in cemented lap joints has become of practical importance because of the development of new methods which permit a strong bond to be established between wood, plastic, or metal sheets, or combinations of them by the use of cement adhesives. In this paper, the problem is divided into two parts, (a) determination of the loads at the edges of the joint; (b) determination of the stresses in the joint due to the applied loads. Solutions are obtained for two limiting cases, i.e., where the cement layer is so thin that its effect on the flexibility of the joint may be neglected; and where the joint flexibility is mainly due to that of the cement layer. In both cases expressions are obtained for the shearing stresses in the cement, and for the normal stresses in the cement in a direction perpendicular to the plane of the joint.
Relations Between the Notched Beam Impact Test and the Static Tension Test
Authors: MacGregor C. W. , Fisher J. C.
Published: March 2021

Results of static tension tests of both notched and uniform bars are compared with notched beam impact tests through the use of true stress-strain values. For the materials tested and under the temperature conditions imposed, it was found that the effect of drawing and testing temperatures on the energy absorbed per unit of volume was essentially the same for both static notched tension and notched beam impact tests.
The Effects of Web Deformation on the Torsion of I-Beams
Authors: Goodier J. N. , Barton M. V.
Published: March 2021

An analysis of the I-beam in nonuniform torsion, as for instance, when a built-in end or section of symmetry is prevented from warping, is made which includes not only the bending of the flanges in their own planes (as considered previously by Timoshenko) but also a deformation of the web cross section. This extends the theory to thinner webs and permits the satisfaction of more general end conditions. Numerical examples worked out for three sections, differing in web thickness only, show that the stress and deformation are significantly modified by the web flexibility when the web is sufficiently thin, and that there are then bending stresses in the web which may be larger than the bending stresses in the flanges. Only the unbuckled state of the web is considered.
Moment-Distribution Analysis for Three-Dimensional Pipe Structures
Authors: DeHart R. C.
Published: March 2021

This paper presents a moment-distribution procedure for determining the moments and shears produced in a three-dimensional pipe structure subjected to expansion resulting from temperature change. From the shears existing in the various members, end reactions can be easily determined. The method offers an advantage over virtual-work methods in that fewer calculations are required, consequently reducing the time involved and the danger of omitting some item in the solution.
Experimental Study of Outflow Effects in a Rotating Turbulated Channel
Authors: Zhang Bo-lun , Zhu Hui-Ren , Liu Cun-Liang , Yao Chun-yi
Published: March 2021

The three-pass turbulated serpentine channel has many applications in internal turbine blade systems. However, the studies on the effects of the outflow ratio are lacking, which decreases the thermal analysis accuracy in such a model. To fill this gap, outflow-ratio experiments are conducted on the Nusselt number distributions of a three-pass turbulated channel. The current experimental results can guide and optimize the turbine blade internal cooling system. The results show with the mass flow of the lateral outlet increasing, the low-heat transfer region on the lateral-outflow passage gradually expands. Increasing the mass flow of the lateral outlet heightens the spanwise-averaged Nusselt number of the lateral-outflow passage, especially under the static condition. In the lateral-outflow passage, the rotation significantly improves the Nusselt number uniformity, particularly at the high mass flowrate of the lateral holes; the rotation shows slight effects on the spanwise-averaged Nusselt number of the lateral-outflow passage at low rotation numbers, whereas the profound influence is observed for the spanwise-averaged Nusselt number under high rotation-number condition. The rotation can profoundly increase the pressure coefficient leading to a reduced pressure loss with the rotation number increasing from 0.03 to 0.06.
Quantifying the Combined Effects of Human Errors and Component Failures
Authors: Irshad Lukman , Hulse Daniel , Demirel H. Onan , Tumer Irem Y. , Jensen David C.
Published: March 2021

While a majority of accidents and malfunctions in complex engineered systems are attributed to human error, a closer inspection would reveal that such mishaps often emerge as a result of complex interactions between the human- and component-related vulnerabilities. To fully understand and mitigate potential risks, the effects of such interactions between component failures and human errors (in addition to their independent effects) need to be considered early. Specifically, to facilitate risk-based design, severity of such failures need to be quantified early in the design process to determine overall risk and prioritize the most important hazards. However, existing risk assessment methods either quantify the risk of component failures or human errors in isolation or are only applicable during later design stages. This work intends to overcome this limitation by introducing an expected cost model to the Human Error and Functional Failure Reasoning (HEFFR) framework to facilitate the quantification of the effects of human error and component failures acting in tandem. This approach will allow designers to assess the risk of hazards emerging from human- and component-related failures occurring in combination and identify worst-case fault scenarios. A coolant tank case study is used to demonstrate this approach. The results show that the proposed approach can help designers quantify the effects of human error and component failures acting alone and in tandem, identify worst-case scenarios, and improve human-product interactions. However, the underlying likelihood and cost models are subject to uncertainties which may affect the assessments.
Phosphites as precursors in atomic layer deposition thin film synthesis
Authors: Kvamme Kristian B. , Ruud Amund , Weibye Kristian , Sajavaara Timo , Nilsen Ola
Published: March 2021

We here demonstrate a new route for deposition of phosphorous based materials by atomic layer deposition (ALD) using the phosphites Me3PO3 or Et3PO3 as precursors. These contain phosphorous in the oxidation state (III) and are open for deposition of reduced phases by ALD. We have investigated their applicability for the synthesis of LiPO and AlPO materials and characterized their growth by means of in situ quartz crystal microbalance. Phosphites are good alternatives to the established phosphate-based synthesis routes as they have high vapor pressure and are compatible with water as a coreactant during deposition. The deposited materials have been characterized using XPS, x-ray fluorescence, and ion beam analysis for composition analysis, spectroscopic ellipsometry for thickness, and FTIR for local structure.
At last, room temperature superconductivity achieved
Authors: Service Robert F.
Published: March 2021

But the hydrogen-based material requires high pressure.
The United Kingdom's mask crusader
Authors: Shell Ellen Ruppel
Published: March 2021

Trisha Greenhalgh argues COVID-19 shows that health policy need not wait for perfect evidence.
Occurrence and Transmission of
bla
NDM
-Carrying
Enterobacteriaceae
from Geese and the Surrounding Environment on a Commercial Goose Farm
Authors: Cen Dao-Ji , Sun Ruan-Yang , Mai Jia-Lin , Jiang Yu-Wei , Wang Dong , Guo Wen-Ying , Jiang Qi , Zhang Hui , Zhang Jin-Fei , Zhang Rong-Min , Sun Jian , Liao Xiao-Ping , Liu Ya-Hong , Fang Liang-Xing
Published: March 2021

Carbapenem-resistant bacteria, in particular NDM-producing
Enterobacteriaceae
, have become a great threat to global public. These bacteria have been found not only in hospital and community environments but also among food animal production chains, which are recognized as reservoirs for NDM-producing
Enterobacteriaceae
.
Air versus Water Chilling of Chicken: a Pilot Study of Quality, Shelf-Life, Microbial Ecology, and Economics
Authors: Belk Aeriel D. , Duarte Toni , Quinn Casey , Coil David A. , Belk Keith E. , Eisen Jonathan A. , Quinn Jason C. , Martin Jennifer N. , Yang Xiang , Metcalf Jessica L.
Published: March 2021

As the poultry industry works to become more sustainable and to reduce the volume of food waste, it is critical to consider points in the processing system that can be altered to make the process more efficient. In this study, we demonstrate that the method used during chilling (air versus water chilling) influences the final product microbial community, quality, and physiochemistry.
Trends in the incidence and management of hypoxic-ischaemic encephalopathy in the therapeutic hypothermia era: a national population study
Authors: Shipley Lara , Gale Chris , Sharkey Don
Published: March 2021

Objective

Hypoxic-ischaemic encephalopathy (HIE) remains a leading cause of neonatal mortality and neurodisability. We aimed to determine the incidence of HIE and management patterns against national guidelines.

Design

Retrospective cohort study using the National Neonatal Research Database.

Setting

Neonatal units in England and Wales.

Patients

Infants 34–42 weeks gestational age (GA) with a recorded diagnosis of HIE.

Main outcomes

Incidence of HIE, mortality and treatment with therapeutic hypothermia (TH) were the main outcomes. Temporal changes were compared across two epochs (2011–2013 and 2014–2016).

Results

Among 407 462 infants admitted for neonatal care, 12 195 were diagnosed with HIE. 8166 infants ≥36 weeks GA had moderate/severe HIE, 62.1% (n=5069) underwent TH and mortality was 9.3% (n=762). Of infants with mild HIE (n=3394), 30.3% (n=1027) underwent TH and 6 died. In late preterm infants (34–35 weeks GA) with HIE (n=635, 5.2%), 33.1% (n=210) received TH and 13.1% (n=83) died. Between epochs (2011–2013 vs 2014–2016), mortality decreased for infants ≥36 weeks GA with moderate/severe HIE (17.5% vs 12.3%; OR 0.69, 95% CI 0.59 to 0.81, p<0.001). Treatment with TH increased significantly between epochs in infants with mild HIE (24.9% vs 35.8%, p<0.001) and those born late preterm (34.3% vs 46.6%, p=0.002).

Conclusions

Mortality of infants ≥36 weeks GA with moderate/severe HIE has reduced over time, although many infants diagnosed with moderate/severe HIE do not undergo TH. Increasingly, mild HIE and late preterm infants with HIE are undergoing TH, where the evidence base is lacking, highlighting the need for prospective studies to evaluate safety and efficacy in these populations.
Association between preconception maternal stress and offspring birth weight: findings from an Australian longitudinal data linkage study
Authors: Harris Melissa L , Hure Alexis J , Holliday Elizabeth , Chojenta Catherine , Anderson Amy E , Loxton Deborah
Published: March 2021

Objective

Examine the relationship between preconception stress and offspring birth weight.

Setting

Population-based cohort study linked with state-based administrative perinatal data.

Participants

6100 births from 3622 women from the 1973–1978 cohort of the Australian Longitudinal Study of Women’s Health who (1) recorded a singleton birth between January 1997 and December 2011; (2) returned at least one follow-up survey within 3 years of conception; and (3) had complete data on perceived stress prior to conception.

Primary outcome measures

Linear generalised estimating equations were used to examine the relationship between preconception stress and a continuous measure of birth weight, exploring differences based on birth order and stress chronicity. The minimal sufficient adjustment set of covariates was determined by a directed acyclic graph.

Results

For all births, there was no relationship between moderate/high acute or chronic stress and offspring birth weight in grams. Among first births only, there was a trend towards a relationship between moderate/high chronic stress and offspring birth weight. Offspring sex was associated with birth weight in all models, with female babies born lighter than male babies on average, after adjusting for covariates (p<0.0001).

Conclusions

Effects of preconception stress on birth weight was largely driven by time to conception. With the timing of stress critical to its impact on obstetrical outcomes, preconception care should involve not only reproductive life planning but the space to provide interventions at critical periods so that optimal outcomes are achieved.
Clinicians’ heuristic assessments of radiographs compared with Kellgren-Lawrence and Ahlbäck ordinal grading: an exploratory study of knee radiographs using paired comparisons
Authors: Pedersen Mads Møller , Geoffroy Mongelard Kristian Breds , Mørup-Petersen Anne , Bang Christensen Karl , Odgaard Anders
Published: March 2021

Objectives

Ordinal scales provide means for communicating the severity of a condition, but they are affected by cognitive biases, they introduce statistical problems and they sacrifice resolution. Clinicians discern more details than contained in scales, for example, when assessing radiographs, but clinicians’ distinctions are often based on experience-based rules of thumb, that is, heuristics. The objectives of this study are to compare clinicians’ heuristic assessments to ordinal grading, to identify case elements that influence clinicians’ judgements and to present a method for quantifying heuristic assessments.

Design

Clinicians were presented with 17 207 random pairs from a set of 1087 knee radiographs. For each pair, the radiograph with more severe osteoarthritis was selected. The Bradley-Terry model was used to calculate an osteoarthritis strength parameter for each radiograph. Similarly, strength parameters were determined for 12 morphological features with five additional features being considered either present or absent. All radiographs were also graded according to conventional ordinal systems (Kellgren-Lawrence and Ahlbäck). Relations between clinicians’ judgements and (1) the heuristics-based osteoarthritis strength, (2) conventional ordinal systems and (3) morphological features were investigated.

Results

Receiver operating characteristic analysis showed that the Bradley-Terry model provided a good description of clinicians’ assessments (area under the curve (AUC)=0.97, 95% CI 0.968 to 0.972). Morphological features (AUC=0.90, 95% CI 0.900 to 0.908) provided a superior description of clinicians’ choices compared with conventional ordinal systems (AUC=0.88, 95% CI 0.878 to 0.887 and AUC=0.80, 95% CI 0.796 to 0.809) for Ahlbäck and Kellgren-Lawrence, respectively). The features most strongly associated with osteoarthritis strength were medial joint space width, flattening of the medial femoral and tibial condyles, medial osteophytes and alignment.

Conclusions

Heuristics-based assessments give a better distinction than conventional grading systems of knee osteoarthritis. The example presents a general approach to evaluate which features are part of experts’ heuristics. The data suggest that experts discern more details than included in conventional ordinal grading systems. Quantitative heuristic assessments may replace ordinal scales.
Modelling COVID-19 transmission in Africa: countrywise projections of total and severe infections under different lockdown scenarios
Authors: Frost Isabel , Craig Jessica , Osena Gilbert , Hauck Stephanie , Kalanxhi Erta , Schueller Emily , Gatalo Oliver , Yang Yupeng , Tseng Katie K , Lin Gary , Klein Eili
Published: March 2021

Objectives

As of 13 January 2021, there have been 3 113 963 confirmed cases of SARS-CoV-2 and 74 619 deaths across the African continent. Despite relatively lower numbers of cases initially, many African countries are now experiencing an exponential increase in case numbers. Estimates of the progression of disease and potential impact of different interventions are needed to inform policymaking decisions. Herein, we model the possible trajectory of SARS-CoV-2 in 52 African countries under different intervention scenarios.

Design

We developed a compartmental model of SARS-CoV-2 transmission to estimate the COVID-19 case burden for all African countries while considering four scenarios: no intervention, moderate lockdown, hard lockdown and hard lockdown with continued restrictions once lockdown is lifted. We further analysed the potential impact of COVID-19 on vulnerable populations affected by HIV/AIDS and tuberculosis (TB).

Results

In the absence of an intervention, the most populous countries had the highest peaks in active projected number of infections with Nigeria having an estimated 645 081 severe infections. The scenario with a hard lockdown and continued post-lockdown interventions to reduce transmission was the most efficacious strategy for delaying the time to the peak and reducing the number of cases. In South Africa, projected peak severe infections increase from 162 977 to 2 03 261, when vulnerable populations with HIV/AIDS and TB are included in the analysis.

Conclusion

The COVID-19 pandemic is rapidly spreading across the African continent. Estimates of the potential impact of interventions and burden of disease are essential for policymakers to make evidence-based decisions on the distribution of limited resources and to balance the economic costs of interventions with the potential for saving lives.
Atorvastatin is unlikely to prevent rheumatoid arthritis in high risk individuals: results from the prematurely stopped STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial
Authors: van Boheemen Laurette , Turk Samina , Beers-Tas Marian van , Bos Wouter , Marsman Diane , Griep Ed N , Starmans-Kool Mirian , Popa Calin D , van Sijl Alper , Boers Maarten , Nurmohamed Michael T , van Schaardenburg Dirkjan
Published: March 2021

Objectives

Persons at high risk of rheumatoid arthritis (RA) might benefit from a low-risk pharmacological intervention aimed at primary prevention. Previous studies demonstrated disease-modifying effects of statins in patients with RA as well as an association between statin use and a decreased risk of RA development. A randomised, double-blind, placebo-controlled trial investigated whether atorvastatin could prevent arthritis development in high-risk individuals.

Methods

Arthralgia patients with anticitrullinated protein antibody (ACPA) >3 xULN or ACPA and rheumatoid factor, without (a history of) arthritis, were randomised to receive atorvastatin 40 mg daily or placebo for 3 years. The calculated sample size was 220 participants. The primary endpoint was clinical arthritis. Cox regression analysis was used to determine the effect of atorvastatin on arthritis development.

Results

Due to a low inclusion rate, mainly because of an unwillingness to participate, the trial was prematurely stopped. Data of the 62 randomised individuals were analysed. Median follow-up was 14 (inner quartiles 6–35) months. Fifteen individuals (24%) developed arthritis: 9/31 (29%) in the atorvastatin group; 6/31 (19%) in the placebo group: HR 1.40, 95% CI 0.50 to 3.95.

Conclusions

In this small set of randomised high-risk individuals, we did not demonstrate a protective effect of atorvastatin on arthritis development. The main reason for the low inclusion was unwillingness to participate; this may also impede other RA prevention trials. Further research to investigate and solve barriers for prevention trial participation is needed.
Modelling the effect of ribosome mobility on the rate of protein synthesis
Authors: Dauloudet Olivier , Neri Izaak , Walter Jean-Charles , Dorignac Jérôme , Geniet Frédéric , Parmeggiani Andrea
Published: March 2021

Translation is one of the main steps in the synthesis of proteins. It consists of ribosomes that translate sequences of nucleotides encoded on mRNA into polypeptide sequences of amino acids. Ribosomes bound to mRNA move unidirectionally, while unbound ribosomes diffuse in the cytoplasm. It has been hypothesized that finite diffusion of ribosomes plays an important role in ribosome recycling and that mRNA circularization enhances the efficiency of translation, see e.g. Lodish et al. (Molecular cell biology, 8th edn, W.H. Freeman and Company, San Francisco, 2016). In order to estimate the effect of cytoplasmic diffusion on the rate of translation, we consider a totally asymmetric simple exclusion process coupled to a finite diffusive reservoir, which we call the ribosome transport model with diffusion. In this model, we derive an analytical expression for the rate of protein synthesis as a function of the diffusion constant of ribosomes, which is corroborated with results from continuous-time Monte Carlo simulations. Using a wide range of biological relevant parameters, we conclude that diffusion is not a rate limiting factor in translation initiation because diffusion is fast enough in biological cells.

Graphic abstract
Flagellar arrangements in elongated peritrichous bacteria: bundle formation and swimming properties
Authors: Clopés Judit , Winkler Roland G.
Published: March 2021

The surface distribution of flagella in peritrichous bacterial cells has been traditionally assumed to be random. Recently, the presence of a regular grid-like pattern of basal bodies has been suggested. Experimentally, the manipulation of the anchoring points of flagella in the cell membrane is difficult, and thus, elucidation of the consequences of a particular pattern on bacterial locomotion is challenging. We analyze the bundle formation process and swimming properties of Bacillus subtilis-like cells considering random, helical, and ring-like arrangements of flagella by means of mesoscale hydrodynamics simulations. Helical and ring patterns preferentially yield configurations with a single bundle, whereas configurations with no clear bundles are most likely for random anchoring. For any type of pattern, there is an almost equally low probability to form V-shaped bundle configurations with at least two bundles. Variation of the flagellum length yields a clear preference for a single major bundle in helical and ring patterns as soon as the flagellum length exceeds the body length. The average swimming speed of cells with a single or two bundles is rather similar, and approximately $$50\%$$

50
%

larger than that of cells of other types of flagellar organization. Considering the various anchoring patterns, rings yield the smallest average swimming speed independent of the type of bundle, followed by helical arrangements, and largest speeds are observed for random anchoring. Hence, a regular pattern provides no advantage in terms of swimming speed compared to random anchoring of flagella, but yields more likely single-bundle configurations.

Graphic abstract
CiliaQ: a simple, open-source software for automated quantification of ciliary morphology and fluorescence in 2D, 3D, and 4D images
Authors: Hansen Jan Niklas , Rassmann Sebastian , Stüven Birthe , Jurisch-Yaksi Nathalie , Wachten Dagmar
Published: March 2021

Cilia are hair-like membrane protrusions that emanate from the surface of most vertebrate cells and are classified into motile and primary cilia. Motile cilia move fluid flow or propel cells, while also fulfill sensory functions. Primary cilia are immotile and act as a cellular antenna, translating environmental cues into cellular responses. Ciliary dysfunction leads to severe diseases, commonly termed ciliopathies. The molecular details underlying ciliopathies and ciliary function are, however, not well understood. Since cilia are small subcellular compartments, imaging-based approaches have been used to study them. However, tools to comprehensively analyze images are lacking. Automatic analysis approaches require commercial software and are limited to 2D analysis and only a few parameters. The widely used manual analysis approaches are time consuming, user-biased, and difficult to compare. Here, we present CiliaQ, a package of open-source, freely available, and easy-to-use ImageJ plugins. CiliaQ allows high-throughput analysis of 2D and 3D, static or time-lapse images from fluorescence microscopy of cilia in cell culture or tissues, and outputs a comprehensive list of parameters for ciliary morphology, length, bending, orientation, and fluorescence intensity, making it broadly applicable. We envision CiliaQ as a resource and platform for reproducible and comprehensive analysis of ciliary function in health and disease.

Graphic abstract
Multiplicity of positive solutions for (p,q)-Laplace equations with two parameters
Authors: Bobkov Vladimir , Tanaka Mieko
Published: March 2021

We study the zero Dirichlet problem for the equation [Formula: see text] in a bounded domain [Formula: see text], with [Formula: see text]. We investigate the relation between two critical curves on the [Formula: see text]-plane corresponding to the threshold of existence of special classes of positive solutions. In particular, in certain neighborhoods of the point [Formula: see text], where [Formula: see text] is the first eigenfunction of the [Formula: see text]-Laplacian, we show the existence of two and, which is rather unexpected, three distinct positive solutions, depending on a relation between the exponents [Formula: see text] and [Formula: see text].
Irreducibility of mod p Galois representations of elliptic curves with multiplicative reduction over number fields
Authors: Najman Filip , Ţurcaş George C.
Published: March 2021

In this paper we prove that for every integer [Formula: see text], there exists an explicit constant [Formula: see text] such that the following holds. Let [Formula: see text] be a number field of degree [Formula: see text], let [Formula: see text] be any rational prime that is totally inert in [Formula: see text] and [Formula: see text] any elliptic curve defined over [Formula: see text] such that [Formula: see text] has potentially multiplicative reduction at the prime [Formula: see text] above [Formula: see text]. Then for every rational prime [Formula: see text], [Formula: see text] has an irreducible mod [Formula: see text] Galois representation. This result has Diophantine applications within the “modular method”. We present one such application in the form of an Asymptotic version of Fermat’s Last Theorem that has not been covered in the existing literature.
Application of Conformable Sumudu Decomposition Method for Solving Conformable Fractional Coupled Burger’s Equation
Authors: Eltayeb Hassan , Mesloub Said
Published: March 2021

The conformable double Sumudu decomposition method (CDSDM) is a combination of decomposition method (DM) and a conformable double Sumudu transform. It is an approximate analytical method, which can be used to solve linear and nonlinear partial differential equations. In this work, one-dimensional conformable functional Burger’s equation has been solved by applying conformable double Sumudu decomposition. Two examples are used to illustrate the method.
Investigating the Effective Factors of Renewable Energy Development in Tehran Metropolis
Authors: Arasteh Taleshmekaiil Mohammad Reza , Khatibi Seyed Mohammad Reza , Mohemsaz Mona , Azimi Mohammad Hossein , Sadeghpour Ali
Published: March 2021

To prepare for the urban development of 2.5 billion people by 2050, the development of low-carbon, resilient, and liveable urban settlements is crucial. Not only do metropolises contribute to global climate change by rapidly emitting and increasing emissions but they themselves are very fragile and vulnerable to these changes. The purpose of this study is to optimize a model for the development of renewable energies in Tehran City and its application in different sectors to achieve sustainability. The research method is according to the type of the applied-developmental study. Information is based on documentation and field methods. Data were collected using a questionnaire from 76 experts and analysed using MICMAC software. The results indicate the fact that the use of public and specific stimuli and incentives for electricity producers to use renewable energy will accelerate the development of renewable energy at the urban level. In order to improve the existing situation, the unsustainable model can be offered to change the situation in favour of the use of new energy at the regional level. Based on the research results, in general, patterns of deployment and development of renewable energies are grouped into five main groups: the use of financial instruments, the use of legal instruments, the development of technology, education and awareness-raising that urban sustainability in the energy sector can be considered based on these four pillars.
Event Driven Duty Cycling with Reinforcement Learning and Monte Carlo Technique for Wireless Network
Authors: Huang Han Yao , Lee Tae-Jin , Youn Hee Yong
Published: March 2021

Reducing transmission delay and maximizing the network lifetime are important issues for wireless sensor networks (WSN). The existing approaches commonly let the nodes periodically sleep to minimize energy consumption, which adversely increases packet forwarding latency. In this study, a novel scheme is proposed, which effectively determines the duty cycle of the nodes and packet forwarding path according to the network condition by employing the event-based mechanism and reinforcement learning technique. This allows low-latency energy-efficient scheduling and reduces the transmission collision between the nodes on the path. The Monte Carlo evaluation method is also adopted to minimize the overhead of the computation of each node in making the decision. Computer simulation reveals that the proposed scheme significantly improves end-to-end latency, waiting time, packet delivery ratio, and energy efficiency compared to the existing schemes including S-MAC and event-driven adaptive duty cycling scheme.
Investigating the Role of BAFF and Its Receptors in Renal Transplant Recipients with Chronic Antibody-Mediated Rejection
Authors: Afzali Shima , Salehi Saeedeh , Shahi Abbas , Esmaeili Marzie , Farashi Bonab Samad , Peykari Azin , Bagherpour Farzaneh , Ansaripour Bita , Soleimanian Tayebeh , Pour-Reza-Gholi Fatemeh , Amirzargar Aliakbar
Published: March 2021

Background. Kidney transplantation is the best treatment option for end stage renal disease (ESRD), but graft rejection is still a big obstacle that occurs in spite of immunosuppressive therapy. B cells are considered as the major reason for renal graft rejection because of antibody production. Due to their roles in B cell function, we intended to evaluate the B cell activating factor (BAFF) and its receptors including BAFF receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and cyclophilin ligand interactor (TACI) in renal transplant patients. Method. The study included 40 kidney allograft patients with cAMR, 40 stable kidney allograft patients, and 8 healthy volunteers with normal kidney function. The percentage and absolute number of CD19+ B cells were analyzed by flow cytometry, the serum level of BAFF was analyzed by ELISA, and mRNA expressions of BAFF and BAFF receptors (BAFF-R, BCMA, and TACI) were measured using quantitative real-time PCR. Results. The percentage and the absolute number of B cells decreased significantly in stable and cAMR patients compared to healthy individuals. The serum level and gene expression of BAFF, as well as the mRNA level of BCMA, were increased significantly in both cAMR and stable patients compared to healthy volunteers. There was an overexpression of TACI mRNA in cAMR patients compared to stable patients. Conclusions. Both soluble protein and mRNA transcript of BAFF increased in transplant recipients. However, BAFF neither at the serum level nor at the mRNA transcript level cannot be a good biomarker for the prediction of cAMR. In addition, expression of TACI, compared to other receptors of BAFF, confers a potential to be used in distinguishing cAMR and stable kidney transplant patients.