bluuebunny/crossref_metadata_2025 huggingface dataset:
Global pediatric radiation therapy in resource‐limited settings
Authors: Hess Clayton B. , Parkes Jeannette , Janssens Geert O. , Lin Chi , Wong Kenneth , Zaghloul Mohamed S. , Marconi Daniel G. , Boterberg Tom , Esiashvili Natia
Published: August 2020

This report provides a summary of the global burden of childhood cancer morbidity and mortality, which disproportionately affects low‐ and middle‐income countries as well as low‐ and middle‐income communities within high‐income countries. We review past successes and current challenges to improving clinical pediatric radiotherapy, education, and research in these regions. The Pediatric Radiation Oncology Society Taskforce in Low‐ and Middle‐Income Countries recently outlined specific aims: (a) to increase access and quality of radiotherapy for children and adolescents afflicted with cancer; (b) to enumerate, engage, and educate a global community of providers of childhood and adolescent radiotherapy; and (c) to create evidence establishing the outcomes of setting‐specific treatment standards of care when first‐world standards are not achievable. This report will improve awareness of these disparities and promote attempts to correct them.
Circulating tumor DNA in neuroblastoma
Authors: Wei Meng , Ye Mujie , Dong Kuiran , Dong Rui
Published: July 2020

As a sympathetic nervous system–derived tumor, aggressive neuroblastoma (NB) is currently attracting interest from researchers seeking diagnostic and prognostic markers via less invasive procedures. The analysis of circulating tumor DNA (ctDNA) in peripheral blood can provide genetic information from multiple tumor lesions and is not dependent on a surgical procedure. The identification of genetic alterations, chromosomal variations, and hypermethylation contained within plasma DNA yields clinical value in the diagnosis, risk stratification, monitoring of treatment effects, and survival prediction for patients. With the widespread application of genome sequencing, droplet digital polymerase chain reaction, and other advanced technologies, the detection of ctDNA may guide therapeutic schedules, enhance the quality of life, and improve the prognosis for patients with NB.
No benefit of Interfant protocols compared to BFM‐based protocols for infants with acute lymphoblastic leukemia. Results from an institution in Argentina
Authors: Pennella Carla L. , Deu María A. , Rossi Jorge G. , Baialardo Edgardo M. , Alonso Cristina N. , Rubio Patricia , Guitter Myriam R. , La Rosa Cristian G. Sánchez , Alfaro Elizabeth M. , Zubizarreta Pedro A. , Felice María S.
Published: July 2020

Background

Infant acute lymphoblastic leukemia (ALL) is an infrequent disease characterized by clinical and biological features related to poor prognosis. Adapted therapies were designed without a clear consensus regarding the best treatment options. We aimed to compare the outcome between infant ALL cases receiving Interfant versus BFM‐based protocols.

Procedure

This is a retrospective observational study. From April 1990 to June 2018, infant ALL cases were enrolled in one of the five consecutive treatment protocols. Clinical, demographic, and biological features and outcome were evaluated. A comparative analysis was performed between Interfant protocols and BFM‐based protocols.

Results

During the studied period, 1913 ALL patients were admitted and 116 (6%) were infants. Treatment administered was: ALL‐BFM’90 (n = 16), 1‐ALL96‐BFM/HPG (n = 7), Interfant‐99 (n = 39), Interfant‐06 (n = 35), and ALLIC‐BFM’2009 (n = 19). The 5‐year event‐free survival probability (EFSp) was 31.9(standard error [SE] 4.6)% for the entire population, with a significant difference among risk groups according to Interfant‐06 criteria (P = .0029). KMT2A‐rearrangement status was the strongest prognostic factor (P = .048), independently of the protocol strategy. The median time for relapse was 24.1 months for patients with minimal residual disease (MRD)‐negative versus 11.5 months for those with MRD‐positive (P = .0386). EFSp and cumulative relapse risk probability (CRRp) were similar. Interfant protocols showed comparable induction (8.1% vs 7.1%, P = .852) and complete remission mortality (21.6% vs 28.6%, P = .438), failing to reduce the relapse rate (48.5% vs 30.7%, P = .149).

Conclusions

Interfant protocols and BFM‐based protocols presented comparable results. The risk group stratification proposed by Interfant‐06 was validated by our results, and MRD seems useful to identify patients with an increased risk of early relapse.
ADAS Sensors and Computing: A 22 Billion Dollar Market in 2025
Authors: Boulay Pierrick , Malaquin Cédric
Published: August 2020

Advanced driving assistance systems (ADAS) based on a combination of sensors and electronic control units (ECUs) have been developed to support the driver. These systems have helped to reduce road fatalities, alert the driver to potential problems and to avoid collisions.
Remdesivir: A beacon of hope from Ebola virus disease to COVID‐19
Authors: Nili Ali , Farbod Abolfazl , Neishabouri Afarin , Mozafarihashjin Mohammad , Tavakolpour Soheil , Mahmoudi Hamidreza
Published: July 2020

Since the emergence of coronavirus disease 2019 (Covid‐19), many studies have been performed to characterize severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and find the optimum way to combat this virus. After suggestions and assessments of several therapeutic options, remdesivir (GS‐5734), a direct‐acting antiviral drug previously tested against Ebola virus disease, was found to be moderately effective and probably safe for inhibiting SARS‐CoV‐2 replication. Finally, on 1 May 2020, remdesivir (GS‐5734) was granted emergency use authorization as an investigational drug for the treatment of Covid‐19 by the Food and Drug Administration. However, without a doubt, there are challenging days ahead. Here, we provide a review of the latest findings (based on preprints, post‐prints, and news releases in scientific websites) related to remdesivir efficacy and safety for the treatment of Covid‐19, along with covering remdesivir history from bench‐to‐bedside, as well as an overview of its mechanism of action. In addition, active clinical trials, as well as challenging issues related to the future of remdesivir in Covid‐19, are covered. Up to the date of writing this review (19 May 2020), there is one finished randomized clinical trial and two completed non‐randomized studies, in addition to some ongoing studies, including three observational studies, two expanded access studies, and seven active clinical trials registered on the clinicaltrials.gov and isrctn.com websites. Based on these studies, it seems that remdesivir could be an effective and probably safe treatment option for Covid‐19. However, more randomized controlled studies are required.
The sociocultural dimension of the Software Process Improvement Manifesto: Pilot validation by experts
Authors: Georgiadou Elli , Siakas Kerstin , Berki Eleni , Estdale John , Rahanu Harjinder , Ross Margaret
Published: July 2020

The Software Process Improvement (SPI) Manifesto is based on three basic values: people, business focus and organisational change underpinning the philosophy of SPI. In turn, these values bring up to date certain SPI principles serving as a foundation for action in software development. The authors of this paper carried out a pilot expert validation of the sociocultural dimension of the sociocultural, technical, economic, environmental, political, legal, ethical and demographic analysis of the SPI Manifesto. Further, the authors report on the rationale and results of the pilot validation of both the survey instrument and the qualitative responses generated by the field experts, targeting to enlighten and reinforce the importance of the sociocultural dimension of the SPI Manifesto in research and development. The related literature review findings and the pilot research study strengthen this target. The pilot study with experts in particular provided stronger indications that the sociocultural dimension is considered of high importance by between 62% and 88% of the respondents, who were IT and computing professionals and software practitioners from academia and industry.
Bioassay studies of Risperidone and its active metabolite in rat dried blood spots and dried plasma spots using LC‐ESI‐MS/MS: Comparison of their pharmacokinetic profiles
Authors: Challa Gangu Naidu , Nimmu Narendra Varma , Bondigalla Ramachandra , Arnipalli Manikanta Swamy
Published: August 2020

A highly sensitive and specific liquid chromatography‐elctrospray ionization tandem mass spectrometry method was developed and validated for rapid determination of risperidone and its active metabolite in rat dried blood spots and dried plasma spots. Chromatographic separation was achieved through ZIC®‐HILIC (250 × 4.6 mm, 5 µm) at 25°C using 10 mM ammonium acetate (pH: 3.0, adjusted with acetic acid) and acetonitrile (12:88, v/v) as a mobile phase. Tandem mass spectrometry detection was performed in positive ion electrospray ionization using multiple reaction monitoring mode to monitor precursor → product ion transitions m/z 411.2→191.1 for Risperidone, m/z 427.2→207.1 for its metabolite (Risperidone‐9‐OH), respectively. The lower limit of quantification of Risperidone and Risperidone‐9‐OH were 0.95 and 0.90 ng/mL in rat dried blood spots, respectively. The developed bioassay method was successfully applied to study the pharmacokinetic profile of Risperidone and Risperidone‐9‐OH using Iloperidone as an internal standard. As per pharmacokinetic studies, Cmax of Risperidone and Risperidone‐9‐OH in dried blood spots was 36.2 and 28.9 ng/mL; and in dried plasma spots was 38.2 and 30.2 ng/mL, respectively. Similarly, tmax of Risperidone and Risperidone‐9‐OH in dried blood spots was 1.4 and 14.7 h; and in dried plasma spots was 1.54 and 15.4 h, respectively.
Effect of gaseous hydrogen sulphide on growth performance and cecal microbial diversity of weaning pigs
Authors: Cui Jia , Wu Fengyang , Yang Xinyu , Liu Tingting , Xia Xueru , Chang Xingfa , Wang Haonan , Sun Lei , Wei Yuchao , Jia Zenghao , Liu Shudong , Han Shuaijuan , Chen Baojiang
Published: July 2020

The purpose of this study was to examine the effect of gaseous hydrogen sulphide on growth performance and cecal microbial diversity in weaning pigs. A total of 24 weaning pigs (Landrace × Yorkshire × Duroc; average body weight = 8.55 ± 0.68 kg；weaning at 28 days) were selected and randomly divided into four groups (six replicates in each group). The piglets were exposed to hydrogen sulphide (0, 5, 10 and 15 mg/m3) during the experiment period, which lasted 28 days in four controlled environmental chambers. The results showed that exposure to hydrogen sulphide reduced the average daily gain (ADG), average daily feed intake (ADFI), and increased the diarrhoea rate of piglets. Hydrogen sulphide could increase the abundance and diversity of intestinal microbiota. The abundance of Firmicutes and Proteobacteria increased and Bacteroides decreased in the treatment groups. Five biomarkers, such as Eubacterium_1coprostanoligenes, Clostridiales, Phascolarctobacterium, Acidaminococcaceae and Ruminococcaceae_UCG_002 were selected by Lefse analysis. Our results reveal that hydrogen sulphide damaged the growth performance and destroyed the microbial bacteria balance of weaning pigs. The concentrations of hydrogen sulphide should fall below 5 mg/m3.
Conclusion
Authors: Ogbebor Binakuromo
Published: July 2020

This chapter presents highlights on how the media covered the press reform debate that followed the News of the World phone hacking scandal. It argues that rather than serve as a democratic public sphere where diverse voices can have proportionate access to the press reform debate, the media used their gatekeeping powers to advance their views while limiting or preventing arguments that were against their self-interest from gaining entrance into the public sphere. This reduced the quality of the debate on press reform by inhibiting the kind of robust deliberations that produce plurality of views. The author recognises the challenge in asking the press to serve as a democratic public sphere during debates about their policy because bias is inevitable, and every organisation or industry may exhibit some level of bias in its own favour. She, therefore, argues that steps to make the press accountable should also come from outside the press. The author advocates non-governmental public reformism as a means of ensuring press accountability.
Hämoadsorption zur Blutreinigung – Unvergleichbarkeit der klinisch angebotenen Verfahren
Authors: Krenn C. G. , Steltzer H.
Published: July 2020

Hintergrund

Im Bereich der Intensivmedizin, aber auch verstärkt in der Herzchirurgie, gewinnt der Einsatz von adsorptiven Blutreinigungstechnologien zur Behandlung von hyperinflammatorischen Zuständen an Bedeutung. Neben dem CytoSorb-Verfahren, das zunehmend klinisch akzeptiert und auch aktuell am häufigsten eingesetzt wird, drängen seit Kurzem weitere Firmen – vor allem aus China – mit ähnlichen Konzepten auf den Markt.

Ziel der Arbeit

Vor diesem Hintergrund soll es Ziel dieses Artikels sein, exemplarisch auf unterschiedliche Aspekte zwischen den am Markt angebotenen Hämoadsorptionsprodukten einzugehen und einen kritischen Blick auf die vorhandene Evidenz zu werfen.

Methoden

Analysiert wurden technische Merkmale, applikationsspezifische Besonderheiten und vorhandene Evidenz der Adsorptionstechnologien CytoSorb® (CytoSorbentsTM Inc., Monmouth Junction, NJ, USA), Jafron® HA-Serie (Jafron Biomedical Co., Guangdong, China) sowie der Biosky® MG-Serie (Biosun® Medical Technology Co., Foshan City, Guangdong Province, China). Nicht einbezogen wurden rein substanzspezifische Verfahren zur Endotoxinelimination (Toraymyxin®, Alteco®).

Ergebnisse

Bei umfassender Analyse dieser Kriterien zeigt sich, dass zwischen den verfügbaren Technologien erhebliche Unterschiede hinsichtlich verwendeter Materialien, Adsorptionscharakteristika, Anwendung und verfügbarer Daten zu Sicherheit und klinischer Erfahrungen bestehen. Darüber hinaus wird deutlich, dass bei Blutreinigungstechnologien nicht nur deren Wirksamkeit unter Berücksichtigung eines Effekt-Preis-Leistungs-Verhältnisses betrachtet werden sollte, sondern insbesondere auch die klinische Sicherheit der einzelnen Verfahren von entscheidender Bedeutung ist.

Diskussion

Unter den analysierten Technologien stellt unserer Ansicht nach derzeit CytoSorb das am besten untersuchte und klinisch am weitesten etablierte Verfahren dar. Darüber hinaus ist darauf hinzuweisen, dass klinische Ergebnisse, insbesondere jedoch auch sicherheitsrelevante Aspekte, aufgrund der technisch unterschiedlichen Verfahren nicht zwischen den Produkten übertragbar sind.
The epistemic opacity of autonomous systems and the ethical consequences
Authors: Héder Mihály
Published: July 2020

This paper takes stock of all the various factors that cause the design-time opacity of autonomous systems behaviour. The factors include embodiment effects, design-time knowledge gap, human factors, emergent behaviour and tacit knowledge. This situation is contrasted with the usual representation of moral dilemmas that assume perfect information. Since perfect information is not achievable, the traditional moral dilemma representations are not valid and the whole problem of ethical autonomous systems design proves to be way more empirical than previously understood.
Integration of airborne gravimetry data filtering into residual least-squares collocation: example from the 1 cm geoid experiment
Authors: Willberg Martin , Zingerle Philipp , Pail Roland
Published: August 2020

Low-pass filters are commonly used for the processing of airborne gravity observations. In this paper, for the first time, we include the resulting correlations consistently in the functional and stochastic model of residual least-squares collocation. We demonstrate the necessity of removing high-frequency noise from airborne gravity observations, and derive corresponding parameters for a Gaussian low-pass filter. Thereby, we intend an optimal combination of terrestrial and airborne gravity observations in the mountainous area of Colorado. We validate the combination in the frame of our participation in ‘the 1 cm geoid experiment’. This regional geoid modeling inter-comparison exercise allows the calculation of a reference solution, which is defined as the mean value of 13 independent height anomaly results in this area. Our result performs among the best and with 7.5 mm shows the lowest standard deviation to the reference. From internal validation we furthermore conclude that the input from airborne and terrestrial gravity observations is consistent in large parts of the target area, but not necessarily in the highly mountainous areas. Therefore, the relative weighting between these two data sets turns out to be a main driver for the final result, and is an important factor in explaining the remaining differences between various height anomaly results in this experiment.
The Liouville theorem for $$p$$-harmonic functions and quasiminimizers with finite energy
Authors: Björn Anders , Björn Jana , Shanmugalingam Nageswari
Published: July 2020

We show that, under certain geometric conditions, there are no nonconstant quasiminimizers with finite pth power energy in a (not necessarily complete) metric measure space equipped with a globally doubling measure supporting a global $$p$$
p
-Poincaré inequality. The geometric conditions are that either (a) the measure has a sufficiently strong volume growth at infinity, or (b) the metric space is annularly quasiconvex (or its discrete version, annularly chainable) around some point in the space. Moreover, on the weighted real line $$\mathbf {R}$$
R
, we characterize all locally doubling measures, supporting a local $$p$$
p
-Poincaré inequality, for which there exist nonconstant quasiminimizers of finite $$p$$
p
-energy, and show that a quasiminimizer is of finite $$p$$
p
-energy if and only if it is bounded. As $$p$$
p
-harmonic functions are quasiminimizers they are covered by these results.
Selective NADH communication from α-ketoglutarate dehydrogenase to mitochondrial transhydrogenase prevents reactive oxygen species formation under reducing conditions in the heart
Authors: Wagner Michael , Bertero Edoardo , Nickel Alexander , Kohlhaas Michael , Gibson Gary E. , Heggermont Ward , Heymans Stephane , Maack Christoph
Published: August 2020

In heart failure, a functional block of complex I of the respiratory chain provokes superoxide generation, which is transformed to H2O2 by dismutation. The Krebs cycle produces NADH, which delivers electrons to complex I, and NADPH for H2O2 elimination via isocitrate dehydrogenase and nicotinamide nucleotide transhydrogenase (NNT). At high NADH levels, α-ketoglutarate dehydrogenase (α-KGDH) is a major source of superoxide in skeletal muscle mitochondria with low NNT activity. Here, we analyzed how α-KGDH and NNT control H2O2 emission in cardiac mitochondria. In cardiac mitochondria from NNT-competent BL/6N mice, H2O2 emission is equally low with pyruvate/malate (P/M) or α-ketoglutarate (α-KG) as substrates. Complex I inhibition with rotenone increases H2O2 emission from P/M, but not α-KG respiring mitochondria, which is potentiated by depleting H2O2-eliminating capacity. Conversely, in NNT-deficient BL/6J mitochondria, H2O2 emission is higher with α-KG than with P/M as substrate, and further potentiated by complex I blockade. Prior depletion of H2O2-eliminating capacity increases H2O2 emission from P/M, but not α-KG respiring mitochondria. In cardiac myocytes, downregulation of α-KGDH activity impaired dynamic mitochondrial redox adaptation during workload transitions, without increasing H2O2 emission. In conclusion, NADH from α-KGDH selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. Therefore, α-KGDH plays a key role for H2O2 elimination, but is not a relevant source of superoxide in heart. In heart failure, α-KGDH/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade. Downregulation of α-KGDH may, therefore, predispose to oxidative stress in heart failure.
The role of hnRNPs in frontotemporal dementia and amyotrophic lateral sclerosis
Authors: Bampton Alexander , Gittings Lauren M. , Fratta Pietro , Lashley Tammaryn , Gatt Ariana
Published: August 2020

Dysregulated RNA metabolism is emerging as a crucially important mechanism underpinning the pathogenesis of frontotemporal dementia (FTD) and the clinically, genetically and pathologically overlapping disorder of amyotrophic lateral sclerosis (ALS). Heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a family of RNA-binding proteins with diverse, multi-functional roles across all aspects of mRNA processing. The role of these proteins in neurodegeneration is far from understood. Here, we review some of the unifying mechanisms by which hnRNPs have been directly or indirectly linked with FTD/ALS pathogenesis, including their incorporation into pathological inclusions and their best-known roles in pre-mRNA splicing regulation. We also discuss the broader functionalities of hnRNPs including their roles in cryptic exon repression, stress granule assembly and in co-ordinating the DNA damage response, which are all emerging pathogenic themes in both diseases. We then present an integrated model that depicts how a broad-ranging network of pathogenic events can arise from declining levels of functional hnRNPs that are inadequately compensated for by autoregulatory means. Finally, we provide a comprehensive overview of the most functionally relevant cellular roles, in the context of FTD/ALS pathogenesis, for hnRNPs A1-U.
Exercise training improves vascular function in patients with Alzheimer’s disease
Authors: Pedrinolla Anna , Venturelli Massimo , Fonte Cristina , Tamburin Stefano , Di Baldassarre Angela , Naro Fabio , Varalta Valentina , Giuriato Gaia , Ghinassi Barbara , Muti Ettore , Smania Nicola , Schena Federico
Published: July 2020

Purpose

Vascular dysfunction has been demonstrated in patients with Alzheimer’s disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD.

Methods

Thirty-nine patients with AD (79 ± 8 years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90 min, 3 t/w). EX included moderate–high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session.

Results

EX group has increased FMD% (+ 3.725%, p < 0.001), PLM ∆peak (+ 99.056 ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825 pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p < 0.05; SR + 134%, p < 0.05), but not during CTRL treatment.

Conclusion

Exercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population.
Dirichlet absorbing boundary conditions for classical and peridynamic diffusion-type models
Authors: Shojaei Arman , Hermann Alexander , Seleson Pablo , Cyron Christian J.
Published: July 2020

Diffusion-type problems in (nearly) unbounded domains play important roles in various fields of fluid dynamics, biology, and materials science. The aim of this paper is to construct accurate absorbing boundary conditions (ABCs) suitable for classical (local) as well as nonlocal peridynamic (PD) diffusion models. The main focus of the present study is on the PD diffusion formulation. The majority of the PD diffusion models proposed so far are applied to bounded domains only. In this study, we propose an effective way to handle unbounded domains both with PD and classical diffusion models. For the former, we employ a meshfree discretization, whereas for the latter the finite element method (FEM) is employed. The proposed ABCs are time-dependent and Dirichlet-type, making the approach easy to implement in the available models. The performance of the approach, in terms of accuracy and stability, is illustrated by numerical examples in 1D, 2D, and 3D.
Memory-based meso-scale modeling of Covid-19
Authors: Kergaßner Andreas , Burkhardt Christian , Lippold Dorothee , Kergaßner Matthias , Pflug Lukas , Budday Dominik , Steinmann Paul , Budday Silvia
Published: August 2020

The COVID-19 pandemic has led to an unprecedented world-wide effort to gather data, model, and understand the viral spread. Entire societies and economies are desperate to recover and get back to normality. However, to this end accurate models are of essence that capture both the viral spread and the courses of disease in space and time at reasonable resolution. Here, we combine a spatially resolved county-level infection model for Germany with a memory-based integro-differential approach capable of directly including medical data on the course of disease, which is not possible when using traditional SIR-type models. We calibrate our model with data on cumulative detected infections and deaths from the Robert-Koch Institute and demonstrate how the model can be used to obtain county- or even city-level estimates on the number of new infections, hospitality rates and demands on intensive care units. We believe that the present work may help guide decision makers to locally fine-tune their expedient response to potential new outbreaks in the near future.
The computational framework for continuum-kinematics-inspired peridynamics
Authors: Javili A. , Firooz S. , McBride A. T. , Steinmann P.
Published: July 2020

Peridynamics (PD) is a non-local continuum formulation. The original version of PD was restricted to bond-based interactions. Bond-based PD is geometrically exact and its kinematics are similar to classical continuum mechanics (CCM). However, it cannot capture the Poisson effect correctly. This shortcoming was addressed via state-based PD, but the kinematics are not accurately preserved. Continuum-kinematics-inspired peridynamics (CPD) provides a geometrically exact framework whose underlying kinematics coincide with that of CCM and captures the Poisson effect correctly. In CPD, one distinguishes between one-, two- and three-neighbour interactions. One-neighbour interactions are equivalent to the bond-based interactions of the original PD formalism. However, two- and three-neighbour interactions are fundamentally different from state-based interactions as the basic elements of continuum kinematics are preserved precisely. The objective of this contribution is to elaborate on computational aspects of CPD and present detailed derivations that are essential for its implementation. Key features of the resulting computational CPD are elucidated via a series of numerical examples. These include three-dimensional problems at large deformations. The proposed strategy is robust and the quadratic rate of convergence associated with the Newton–Raphson scheme is observed.
Trends in temperature and precipitation extremes in historical (1961–1990) and projected (2061–2090) periods in a data scarce mountain basin, northern Pakistan
Authors: Saddique Naeem , Khaliq Abdul , Bernhofer Christian
Published: July 2020

This study investigates the trends of precipitation and temperature extremes for the historical observations (1961–1990) and future period (2061–2090) in the Jhelum River Basin.
Future trends are estimated by using ensemble mean of three general circulation models under RCP4.5 and RCP8.5. Therefore, statistical downscaling model has been used to downscale the future precipitation and temperature. A total of 15 precipitation and temperature indices were calculated using the RClimdex package. Man-Kendall and Sen’s slope tests were used to detect the trends in climate extreme indices. Overall, the results of study indicate that there were significant changes in precipitation and temperature patterns as well as in the climate extremes in the basin for both observed as well as projected climate. Generally, more warming and increase in precipitation were observed, which increases from RCP4.5 to RCP8.5. For all the stations, increasing trends were found for both precipitation and temperature for twenty-first century at a 95% significance level. The frequency of warm days (TX90p), warm nights (TN90p), and summer days (SU25) showed significant increasing trends, alternatively the number of cold nights (TN10p) and cold days (TX10p) exhibited opposite behaviors. In addition, an increasing trend of warmest day (TXx) and coldest day (TNn) was observed. Our analysis also reveals that the number of very wet days (R90p) and heavy precipitation days (R10 mm) will likely increase in the future. Meanwhile, the Max 1-day (RX1-day) and 5-day (RX5-day) precipitation indices showed increasing trends at most of the stations of basin. The results of the study is of potential benefit for decision-makers to develop basin wide appropriate mitigation and adaptation measures to combat climate change and its consequences.
Predicting preoperative pulmonary function in patients with thoracic adolescent idiopathic scoliosis from spinal and thoracic radiographic parameters
Authors: Farrell James , Garrido Enrique
Published: July 2020

Purpose

The objective was to analyse the effect of thoracic morphology on pulmonary function in adolescent idiopathic scoliosis (AIS) to predict preoperative lung function.

Methods

A total of 170 consecutive preoperative patients (average age 15.1 years) with Lenke 1 and 2 AIS underwent pulmonary function testing. Thirteen deformity parameters, including rib hump size, rib asymmetry, spinal intrusion and thoracic/lung dimensions in the sagittal and coronal plane, were measured on whole-spine radiographs. Lung function parameters were expressed as z-scores. Correlation and regression analysis of these parameters with lung function were performed.

Results

Mean thoracic Cobb (MT) was 69.1°, and mean T5–T12 thoracic kyphosis (TK) was 21.8°. MT correlated significantly with FEV1 and FVC (rs = − 0.40 and − 0.38). TK correlated weakly with FEV1 and FEV1/FVC (rs = 0.23 and 0.25). FEV1 and FVC were best predicted by the inverse apical vertebra body–rib ratio (AVBRr−1, rs = 0.46 and 0.42), rib hump depth index (RHDi, rs = − 0.52 and − 0.50) and spinal intrusion ratio (SIr, rs = − 0.50 and − 0.45). The kyphosis–lordosis index (KLi) correlated with FEV1/FVC (rs = 0.29). Multivariate regression analysis of coronal and sagittal Cobb angles produced a model which explained 35% and 30% of the variance in FEV1 and FVC, whilst a regression model consisting of AVBRr−1 and SIr was able to predict 54% and 48%.

Conclusion

AVBRr−1, RHDi and SIr measured on posterior–anterior and lateral radiographs provide better estimations of lung function in preoperative AIS patients than Cobb measurements. KLi was an indicator of airway obstruction as measured by FEV1/FVC.
A new self-designed “tongue root holder” device to aid fiberoptic intubation
Authors: Cao Xiaofei , Wu Junbei , Fang Yin , Ding Zhengnian , Qi Tao
Published: August 2020

Objective

In this study, we aimed to assess the feasibility of fiberoptic intubation (FOI), using a new, self-designed, “tongue root holder” device, in combination with the jaw thrust maneuver.

Methods

Three hundred patients undergoing elective surgery requiring orotracheal intubation were enrolled. Patients presented at least one or more risk factors for difficult airway. The patients were randomly allocated at a 1:1 ratio to one of two groups: group L, FOI with tongue root holder, or group C, standard FOI. Orotracheal FOI was performed after commencement of anesthesia. The jaw thrust maneuver was applied in both groups to facilitate advancement of the fiberoptic bronchoscope. The primary endpoint was the feasibility of FOI. The secondary endpoints were number of attempts, time to intubation, and airway clearance at the soft palate and epiglottis levels.

Results

The FOI was achieved in all 150 patients in group L, significantly higher than that in group C (100% vs 95.3%; P = 0.015). Less attempts of intubation were made in group L (P = 0.039). Mean time to successful intubation on the first attempt was shorter in group L (P < 0.001). The mean times to view the vocal cord and carina were also shorter in group L (P = 0.011 and P < 0.001, respectively). Airway clearance was better in group L at both the soft palate and the glottis levels (P = 0.010 and P = 0.038, respectively).

Conclusions

This study shows that FOI is feasible with the newly introduced, self-designed, “tongue root holder” device, when combined with the jaw thrust maneuver in patients with risk factors for difficult airway. The device also provides better airway clearance, less intubation attempts, and shorter time to intubation at first attempt.

Clinical relevance

Fiberoptic bronchoscope has been the gold standard for routine management of difficult airway. A technique to open the airway is introduced to reduce the incidence rate of upper airway obstruction.
Persistence and regredience of intraspinal fluid collection determine symptom control in intracranial hypotension syndrome
Authors: Schnellbächer Gereon Johannes , Mull Michael , Reich Arno
Published: August 2020

Background and purpose

An intraspinal fluid collection (ISFC) can be observed on spinal MRI in cases of intracranial hypotension syndrome (IHS). The goal of this study was to analyze the possible persistence of ISFC after therapy and its correlation to clinical disease activity and secondary complications.

Materials and methods

Twenty patients in our database of 57 patients, who were treated for IHS between 2009 and 2015, fulfilled the inclusion criteria of (a) diagnosed and treated IHS as well as (b) an ISFC in MRI imaging. Ten of these participated in our study. We performed follow-up visits, which included a history, a clinical examination, and a spinal MRI.

Results

A MRI-confirmed ISFC was seen in six patients, five of which had symptoms attributable to chronic IHS. There were two cases of superficial siderosis. One patient had a persisting ISFC and was free of symptoms. Four patients did not have an ISFC and were free of symptoms (Fisher’s exact test; p < 0.048).

Conclusion

There is statistically significant correlation between the persistence of an ISFC after IHS treatment and ongoing clinical symptoms. Resolved symptoms seem to correlate with absorbed extradural ISFC and hypothetically closed leakage site. ISFC as confirmed by MRI proofs to be a reliable follow-up marker for disease activity in chronic IHS that is possibly even superior to clinical examination.
The AirSeal® insufflation device can entrain room air during routine operation
Authors: Weenink R. P. , Kloosterman M. , Hompes R. , Zondervan P. J. , Beerlage H. P. , Tanis P. J. , van Hulst R. A.
Published: July 2020

Background

Surgical procedures that use insufflation carry a risk of gas embolism, which is considered relatively harmless because of the high solubility of carbon dioxide. However, an in vitro study suggested that valveless insufflation devices may entrain non-medical room air into the surgical cavity. Our aim was to verify if this occurs in actual surgical procedures.

Methods

The oxygen percentage in the pneumoperitoneum or pneumorectum/pneumopelvis of eight patients operated with use of the AirSeal® was continuously measured, to determine the percentage of air in the total volume of the surgical cavity.

Results

Basal air percentage in the surgical cavity was 0–5%. During suctioning from the operative field air percentage increased to 45–65%.

Conclusions

The AirSeal® valveless insufflation device maintains optimal distension of the surgical cavity not only by insufflating carbon dioxide, but also by entraining room air, especially during suctioning from the operative field. This may theoretically lead to air embolism in patients operated on with this device.
Miniaturization of fluorescence sensing in optofluidic devices
Authors: Măriuţa Daniel , Colin Stéphane , Barrot-Lattes Christine , Le Calvé Stéphane , Korvink Jan G. , Baldas Lucien , Brandner Jürgen J.
Published: August 2020

Successful development of a micro-total-analysis system (µTAS, lab-on-a-chip) is strictly related to the degree of miniaturization, integration, autonomy, sensitivity, selectivity, and repeatability of its detector. Fluorescence sensing is an optical detection method used for a large variety of biological and chemical assays, and its full integration within lab-on-a-chip devices remains a challenge. Important achievements were reported during the last few years, including improvements of previously reported methodologies, as well as new integration strategies. However, a universal paradigm remains elusive. This review considers achievements in the field of fluorescence sensing miniaturization, starting from off-chip approaches, representing miniaturized versions of their lab counter-parts, continuing gradually with strategies that aim to fully integrate fluorescence detection on-chip, and reporting the results around integration strategies based on optical-fiber-based designs, optical layer integrated designs, CMOS-based fluorescence sensing, and organic electronics. Further successful development in this field would enable the implementation of sensing networks in specific environments that, when coupled to Internet-of-Things (IoT) and artificial intelligence (AI), could provide real-time data collection and, therefore, revolutionize fields like health, environmental, and industrial sensing.
A joke on precision? Revisiting “precision” in the school mathematics discourse
Authors: Ryan Ulrika , Chronaki Anna
Published: July 2020

This paper discusses the place of precision in mathematics education by exploring its role in curricular guidelines and in classroom life. By means of a joke on precision delivered by a school student in South Sweden, our study focuses on student participation in mathematical tasks that require precision in processes of measuring and reasoning. The paper uses theories on humour and inferentialism to revisit the normative place of “precision” in mathematics classroom discourse.
Hartz and Minds: Happiness Effects of Reforming an Employment Agency
Authors: Deter Max
Published: July 2020

Since the labor market reforms around 2005, known as the Hartz reforms, Germany has experienced declining unemployment rates. However, little is known about the reforms’ effect on individual life satisfaction of unemployed workers. This study applies difference-in-difference estimations and finds a decrease in life satisfaction after the reforms that is more pronounced for male unemployed in west Germany. The effect is driven by income and income satisfaction, but not by the unemployment rate. Also unemployed persons who exogenously lost their jobs are affected by the reforms. In line with the structure of the reforms, the effect is stronger on long-term and involuntarily unemployed persons.
The physics of representation
Authors: Poldrack Russell A.
Published: July 2020

The concept of “representation” is used broadly and uncontroversially throughout neuroscience, in contrast to its highly controversial status within the philosophy of mind and cognitive science. In this paper I first discuss the way that the term is used within neuroscience, in particular describing the strategies by which representations are characterized empirically. I then relate the concept of representation within neuroscience to one that has developed within the field of machine learning (in particular through recent work in deep learning or “representation learning”). I argue that the recent success of artificial neural networks on certain tasks such as visual object recognition reflects the degree to which those systems (like biological brains) exhibit inherent inductive biases that reflect the structure of the physical world. I further argue that any system that is going to behave intelligently in the world must contain representations that reflect the structure of the world; otherwise, the system must perform unconstrained function approximation which is destined to fail due to the curse of dimensionality, in which the number of possible states of the world grows exponentially with the number of dimensions in the space of possible inputs. An analysis of these concepts in light of philosophical debates regarding the ontological status of representations suggests that the representations identified within both biological and artificial neural networks qualify as legitimate representations in the philosophical sense.
Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons
Authors: Kent Clement , Agrawal Pavan
Published: August 2020

Transcriptional and epigenetic regulation of both dopaminergic neurons and their accompanying glial cells is of great interest in the search for therapies for neurodegenerative disorders such as Parkinson’s disease (PD). In this review, we collate transcriptional and epigenetic changes identified in adult Drosophila melanogaster dopaminergic neurons in response to either prolonged social deprivation or social enrichment, and compare them with changes identified in mammalian dopaminergic neurons during normal development, stress, injury, and neurodegeneration. Surprisingly, a small set of activity-regulated genes (ARG) encoding transcription factors, and a specific pattern of epigenetic marks on gene promoters, are conserved in dopaminergic neurons over the long evolutionary period between mammals and insects. In addition to their classical function as immediate early genes to mark acute neuronal activity, these ARG transcription factors are repurposed in both insects and mammals to respond to chronic perturbations such as social enrichment, social stress, nerve injury, and neurodegeneration. We suggest that these ARG transcription factors and epigenetic marks may represent important targets for future therapeutic intervention strategies in various neurodegenerative disorders including PD.
Taking Preprimary Programs to Scale in Developing Countries: Multi-source Evidence to Improve Primary School Completion Rates
Authors: Crouch Luis , King Katherine , Olefir Anna , Saeki Hiroshi , Savrimootoo Tanya
Published: August 2020

The paper argues that in many developing countries there is a set of linked symptoms in education systems that cohere into what we call a weak foundations syndrome. Multi-source evidence is presented to illustrate how weak foundations through the early years of schooling lead to low primary school completion. Symptoms of the syndrome include (1) low access, use, and quality in preprimary programs; (2) permanently high apparent rate of intake (above 100%) into grade 1; (3) over-enrollment bulge, in the early grades, as well as formal and informal grade repetition through primary school; (4) apparent large enrollment drop-off between grades 1 and 2. Small stories for Burundi, Madagascar, and Ethiopia are presented to illustrate the syndrome. These cases also identify how countries and international organizations are starting to address the issues. An interesting aspect of the findings is the data that show parents’ support for preprimary education by enrolling their children earlier than the normative age for grade 1.
No impact of a prescription booklet on medication consumption in nursing home residents from 2011 to 2014: a controlled before–after study
Authors: Sanchez Stéphane , Payet Cécile , Herr Marie , Ecarnot Fiona , Blochet Caroline , Armaingaud Didier , Chrusciel Jan , Novella Jean-Luc , Mahmoudi Rachid
Published: August 2020

Background

Older persons are particularly exposed to adverse events from medication. Among the various strategies to reduce polypharmacy, educational approaches have shown promising results. We aimed to evaluate the impact on medication consumption, of a booklet designed to aid physicians with prescriptions for elderly nursing home residents.

Methods

Among 519 nursing homes using an electronic pill dispenser, we recorded the daily number of times that a drug was administered for each resident, over a period of 4 years. The intervention group comprised 113 nursing homes belonging to a for-profit geriatric care provider that implemented a booklet delivered to prescribers and pharmacists and specifically designed to aid with prescriptions for elderly nursing home residents. The remaining 406 nursing homes where no such booklet was introduced comprised the control group. Data were derived from electronic pill dispensers. The effect of the intervention on medication consumption was assessed with multilevel regression models, adjusted for nursing home status. The main outcomes were the average daily number of times that a medication was administered and the number of drugs with different presentation identifier codes per resident per month.

Results

96,216 residents from 519 nursing homes were included between 1 January 2011 and 31 December 2014. The intervention group and the control group both decreased their average daily use of medication (− 0.05 and − 0.06). The booklet did not have a statistically significant effect (exponentiated difference-in-differences coefficient 1.00, 95% confidence interval 0.99–1.02, P = .45).

Conclusion

We observed an overall decrease in medication consumption in both the control and intervention groups. Our analysis did not provide any evidence that this reduction was related to the use of the booklet. Other factors, such as national policy or increased physician awareness, may have contributed to our findings.
APOE ε4 allele modified the correlation between deep grey matter volume and cognitive performance in non-demented elders
Authors: Li Weiping , Xie Yu , Yu Tingting , Wu Wenbo , Wang Kun , Wu Sichu , Qing Zhao , Zhang Xin , Li Ming , Liu Renyuan , Yin Zhenyu , Zhang Bing
Published: August 2020

APOE ε4 allele is the strongest predictor of Alzheimer’s disease (AD) risk, but its role in the association between the deep grey matter volume and cognitive impairment is still unclear. This study investigated the effects of APOE ε4 allele on this association in non-demented elders. We enrolled 24 patients with mild cognitive impairment (MCI) and 28 normal controls (NC), who underwent the whole brain 3DTIW MRI scanning, an APOE genotype test, and neuropsychological tests. The right thalamus (p = 0.026), the left pallidum (p = 0.026), and the bilateral amygdala (left p = 0.042, right p = 0.048) atrophied in MCI, and their volume were positively correlated with the cognitive scores (MoCA) (p < 0.05). Furthermore, the general liner regression model suggested that the correlation between the right thalamus and the putamen volume with MoCA scores was different in the APOE ε4 carriers and non- carriers. Compared with the non APOEε4 carriers, the right thalamus atrophied more rapidly when the cognition decline in APOE ε4 carriers, while the right putamen compensatory expansion to slow the rate of cognitive decline although failed. This suggested that the right putamen showed stronger compensation by increasing the volume at the early stage of cognitive impairments in the APOE ε4 carriers, while this compensatory change had been disappeared in the right thalamus. In conclusion, APOE ε4 allele modifies the correlation between the right thalamus, the right putamen, and MoCA scores, and it has a potential selective effect on the relationship between cognition and brain structures to some extent in non-demented elders.