bluuebunny/crossref_metadata_2025 huggingface dataset:
Socializing the Gut in Probiotics Experimentation: Calibrating Microbiota and Science Policy
Authors: Gruber David R. , Kalin Jason
Published: December 2019

Prebiotic and probiotic products continue to experience strong consumer growth while gastroenterological researchers work behind the scenes to understand the effects of specific bacterial strains on study participants’ feelings of mind‐body healthfulness. Correlations are achieved through the use of psychometric questionnaires, which aim to measure affect states like stress, anxiety, and depression. In this paper, we turn to qualitative textual analysis to examine two commonly employed psychometric questionnaires (HAM‐D and HADS) used in studies of the same probiotic formulation. We show how concepts of social deviance and norms of behavior (e.g., sleep patterns, social life, and work productivity) inform such questionnaires, thus inserting normative ethical imperatives into clinical findings. After demonstrating several key disjunctions across these questionnaires, we develop recommendations for gastroenterological researchers. In particular, we recommend that researchers give more focused attention to aligning psychometric questionnaires and more carefully enact their qualitative assessment requirements. In like manner, we recommend that ethical reviewers and science policy reviewers consider how psychometric questionnaires embed social assumptions into clinical trials, which can affect determinations of healthfulness.
Synthesis and Upconversion Luminescence in LaF3:Yb3+, Ho3+, GdF3: Yb3+, Tm3+ and YF3:Yb3+, Er3+ obtained from Sulfide Precursors
Authors: Razumkova Illariia A. , Denisenko Yuriy G. , Boyko Andrey N. , Ikonnikov Denis A. , Aleksandrovsky Aleksandr S. , Azarapin Nikita O. , Andreev Oleg V.
Published: December 2019

Rare earth fluorides are mainly obtained from aqueous solutions of oxygen‐containing precursors. Probably, this method is simple and efficient, however, oxygen may partially be retained in the fluoride structure. We offer an alternative method: obtaining fluorides and solid solutions based on them from an oxygen‐free precursor. As starting materials, we choose sulfides of rare‐earth elements and solid solutions based on them. The fluorination is carried out by exposure to hydrofluoric acid of various concentrations. The transmission electron microscopy images revealed the different morphologies of the products, which depend on the concentration of the fluorinating component (HF) and the host element. The solid solution particle size varied from 30–35 nm in the case of GdF3:Yb3+, Tm3+ (4 % HF) to larger structures with dimensions exceeding 200 nm, such as that for LaF3:Yb3+, Ho3+ (40 % HF). The thermal characteristics, such as the temperatures of the transitions and melting and enthalpies, were determined for the solid solutions and simple fluorides. Applicability of the materials obtained as biological luminescent markers was tested on the example of upconversion luminescence, and good upconversion properties were detected.
Lewis Fry Richardson: A Personal Narrative
Authors: Zinnes Dina A.
Published: December 2019

This chapter is the personal story of how the author, just out of graduate school, encountered Richardson’s two posthumous volumes, Arms and Insecurity and Statistics of Deadly Quarrels, and how these volumes helped her resolve key issues that had troubled her. What is theory and how does it differ from a model? The first volume pushed her to learn mathematics and, through various twists and turns, eventually to an understanding of the power of a mathematically written story. The second volume provided insights into data collection and measurement as well as a deeper understanding of the mechanics of mathematical modeling. Thus, the two volumes together gave her the basis for finally answering the questions from her graduate school days.
The Influence of the Richardson Arms Race Model
Authors: Smith Ron P.
Published: December 2019

This chapter reviews the Richardson arms race model: a pair of differential equations which capture an action reaction process. Whereas many of Richardson’s equations were quite specific about what they referred to, the arms race model was not. This lack of specificity was both a strength and a weakness. Its strength was that with different interpretations it could be applied as an organising structure in a wide variety of contexts. Its weakness was that the model could not be estimated or tested without some auxiliary interpretation. The chapter considers the impact of these issues in interpretation and empirical application on the influence of the Richardson arms race model.
What Richardson Got Right (and Wrong) About Arms Races and War
Authors: Diehl Paul F.
Published: December 2019

This chapter considers Richardson’s classic arms race model and his book Arms and Insecurity in relation to the association between arms races and war. The analysis begins with a short review of the academic debates and empirical research about arms races and war. This is a prelude to an examination of the dynamics of arms races as they are specified by Richardson in his book and in his arms race model. Following is an evaluation of the specific claims about arms races and war derived from the model as well as Richardson’s own empirical analyses about the connection between the two phenomena. Although in light of subsequent research, a number of Richardson’s arguments seem misguided or inaccurate, other insights were validated by later studies or remain understudied but worthy of future research.
Back to the Future: Richardson’s Multilateral Arms Race Model
Authors: Ward Michael D.
Published: December 2019

Lewis Fry Richardson was a groundbreaking scholar, not only in modern meteorology but also in world affairs. His two major books, both published posthumously in 1960, were harbingers for what was to follow in scholarly international relations. In one, he collected wide-ranging, detailed quantitative information on disaggregated conflict processes in a variety of historical contexts. In the other, he showed two basic innovations for the social sciences: (a) the power of mathematics for understanding complex social systems and (b) the importance of understanding the interdependence of things that are typically studied separately. That latter insight is the focus of this chapter wherein I show that the Richardsonian insight on coupled behaviors leads to a network perspective on social interactions at the global scale. We call these coupled interactionsnetworks. I trace the development of Richardson’s thinking about coupled phenomena to the development of network thinking in the social sciences. I conclude with some recommendations for the arms race research program as applied to the current era.
Initial conditions for electron and photon structure and fragmentation functions
Authors: Frixione S.
Published: December 2019

Abstract

In the computation of short-distance cross sections initiated by electrons and photons one can adopt the so-called structure-function approach, in which these particles play formally the same roles as hadrons do in QCD factorisation theorems, and must thus be associated with PDFs (equivalently known as structure functions in this context). At variance with their QCD counterparts, such PDFs are entirely calculable in QED. In this paper we present the results, at the next-to-leading order in the QED coupling constant α, for the initial conditions of the unpolarised electron and photon PDFs, which are a nec- essary ingredient for their eventual collinear evolution at the next-to-leading logarithmic accuracy. We also compute the analogous final-state quantities, namely the initial condi- tions for fragmentation functions into electrons and photons.
Forbidden frozen-in dark matter
Authors: Darmé L. , Hryczuk A. , Karamitros D. , Roszkowski L.
Published: December 2019

Abstract

We examine and point out the importance of a regime of dark matter pro- duction through the freeze-in mechanism that results from a large thermal correction to a decaying mediator particle mass from hot plasma in the early Universe. We show that mediator decays to dark matter that are kinematically forbidden at the usually considered ranges of low temperatures can be generically present at higher temperatures and actually dominate the overall dark matter production, thus leading to very distinct solutions from the standard case. We illustrate these features by considering a dark Higgs portal model where dark matter is produced via decays of a scalar field with a large thermal mass. We identify the resulting ranges of parameters that are consistent with the correct dark matter relic abundance and further apply current and expected future collider, cosmological, and astrophysical limits.
The integrated stress response promotes B7H6 expression
Authors: Obiedat Akram , Charpak-Amikam Yoav , Tai-Schmiedel Julie , Seidel Einat , Mahameed Mohamed , Avril Tony , Stern-Ginossar Noam , Springuel Lorraine , Bolsée Jennifer , Gilham David E. , Dipta Priya , Shmuel Miriam , Chevet Eric , Mandelboim Ofer , Tirosh Boaz
Published: December 2019

The B7 family member, B7H6, is a ligand for the natural killer cell receptor NKp30. B7H6 is hardly expressed on normal tissues, but undergoes upregulation on different types of tumors, implicating it as an attractive target for cancer immunotherapy. The molecular mechanisms that control B7H6 expression are poorly understood. We report that in contrast to other NK cell ligands, endoplasmic reticulum (ER) stress upregulates B7H6 mRNA levels and surface expression. B7H6 induction by ER stress requires protein kinase R-like ER kinase (PERK), one of the three canonical sensors of the unfolded protein response. PERK phosphorylates eIF2α, which regulates protein synthesis and gene expression. Because eIF2α is phosphorylated by several kinases following different stress conditions, the program downstream to eIF2α phosphorylation is called the integrated stress response (ISR). Several drugs were reported to promote the ISR. Nelfinavir and lopinavir, two clinically approved HIV protease inhibitors, promote eIF2α phosphorylation by different mechanisms. We show that nelfinavir and lopinavir sustainably instigate B7H6 expression at their pharmacologically relevant concentrations. As such, ER stress and ISR conditions sensitize melanoma targets to CAR-T cells directed against B7H6. Our study highlights a novel mechanism to induce B7H6 expression and suggests a pharmacological approach to improve B7H6-directed immunotherapy.

Key messages

B7H6 is induced by ER stress in a PERK-dependent mechanism.

Induction of B7H6 is obtained pharmacologically by HIV protease inhibitors.

Exposure of tumor cells to the HIV protease inhibitor nelfinavir improves the recognition by B7H6-directed CAR-T.
Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China
Authors: Peng K. , Yao P. , Yang L. , Kartsonaki C. , Bennett D. , Tian M. , Guo Y. , Bian Z. , Chen Y. , Chen Z. , Woodward M. , Ivers R. , Clarke R.
Published: December 2019

This prospective study of Chinese adults demonstrated an inverse J-shaped association of number of children with risk of hip fracture in both men and postmenopausal women aged 50 years or older. Women with 2 or 3 children and men with 4 children had the lowest risk of hip fracture.

Introduction

Women have higher absolute risks of fracture than men, which is believed to reflect differences in oestrogen exposure. The aim of this study was to compare the associations of number of children with risk of hip fracture between men and women aged over 50 years.

Methods

The China Kadoorie Biobank (CKB) recruited 133,399 women and 110,296 men, aged 50 years or older between 2004 and 2008. During 10-year follow-up, 2068 participants (1394 women and 674 men) suffered a hip fracture. Cox regression analysis was used to estimate sex-specific adjusted hazard ratios (HRs) and 95% CI for incident hip fracture.

Results

Over 98% of both subsets of men and women aged 50 or older reported having children. Women who had 2 or 3 children had the lowest risks of hip fracture compared with other groups. Compared with nulliparous women, the adjusted HR for hip fracture were 0.89 (95% CI; 0.72, 1.10) for 1 child, 0.79 (0.70, 0.90) for 2 children, 0.79 (0.72, 0.87) for 3 children, 0.81 (0.72, 0.91) for 4 children, and 0.95 (0.83, 1.10) for those with 5 or more children. The associations of number of children with hip fracture were broadly consistent in men of a similar age.

Conclusions

The concordant effects of the number of children with risk of hip fracture between men and women suggest that the lower risks in multiparous women are not due to differences in oestrogen exposure or other biological effects, but may reflect residual confounding by socioeconomic or lifestyle factors.
Mechanisms of immune evasion in bladder cancer
Authors: Crispen Paul L. , Kusmartsev Sergei
Published: December 2019

With the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway). While these trials have demonstrated promising results and improvements over existing therapies, less than half of patients with advanced disease demonstrate clinical benefit from checkpoint inhibitor therapy. Recent breakthroughs in cancer biology and immunology have led to an improved understanding of the influence of the tumor microenvironment on the host’s immune system. It appears that tumors promote the formation of highly immunosuppressive microenvironments preventing generation of effective anti-tumor immune response through multiple mechanisms. Therefore, reconditioning of the tumor microenvironment and restoration of the competent immune response is essential for achieving optimal efficacy of cancer immunotherapy. In this review, we aim to discuss the major mechanisms of immune evasion in bladder cancer and highlight novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes.
Oral vinorelbine versus intravenous vinorelbine, in combination with epirubicin as first-line chemotherapy in Chinese patients with metastatic breast cancer
Authors: Huang Liang , Wang Xiaojia , Zhou Liheng , Di Lijun , Zheng Hongyu , Jiang Zefei , Wang Yongsheng , Song Xiangqun , Feng Jifeng , Yu Shiying , Liu Yunpeng , Zheng Hong , Shen Kunwei , Tong Zhongsheng , Shao Zhimin
Published: December 2019

Oral VRL offers easier administration, better quality of life, and cost saving. This study aimed to evaluate the treatment efficacy in terms of tumor response of the two formulations of vinorelbine (VRL, oral and IV) in combination with epirubicin (EPI); and the effect of EPI co-administration on VRL pharmacokinetics (PK) in Chinese patients with metastatic breast cancer (MBC) using a phase 2, open label, randomized trial. Patients were aged 18–70 years, had histologically confirmed MBC, Karnofsky Performance Status ≥ 70%, and life expectancy ≥ 12 weeks. The treatment consisted of 6 cycles of 3 weeks each. VRL dose was: (Oral-VRL) 60 mg/m2 for cycle 1, 80 mg/m2 for cycles 2–6, and (IV-VRL) 25 mg/m2 for cycle 1 and 30 mg/m2 for cycles 2–6. EPI dose of 75 mg/m2 was given on day 1 in both arms for all cycles. 133 patients were enrolled: 66 in Oral-VRL and 67 in IV-VRL arms. The median age for Oral-VRL and IV-VRL arms was 48.4 and 50.0 years, respectively. Objective response rates were 50.0% (95% CI 37.4–62.6%) for Oral-VRL and 53.7% (95% CI 41.1–66.0%) for IV-VRL. Both treatment arms met the efficacy objective target of at least 31 responses, demonstrating efficacy as first-line treatment for MBC. Similar blood PK profiles, exposures, and VRL clearance were observed between VRL + EPI vs VRL-only modalities for both arms. Oral VRL is comparable to IV VRL and an effective first-line treatment for Chinese patients with MBC. The activity of VRL + EPI combination is unaltered when VRL is given orally at recommended doses.
Time-saving opportunities in knee osteoarthritis: T2 mapping and structural imaging of the knee using a single 5-min MRI scan
Authors: Eijgenraam Susanne M. , Chaudhari Akshay S. , Reijman Max , Bierma-Zeinstra Sita M. A. , Hargreaves Brian A. , Runhaar Jos , Heijboer Frank W. J. , Gold Garry E. , Oei Edwin H. G.
Published: December 2019

Objectives

To assess the discriminative power of a 5-min quantitative double-echo steady-state (qDESS) sequence for simultaneous T2 measurements of cartilage and meniscus, and structural knee osteoarthritis (OA) assessment, in a clinical OA population, using radiographic knee OA as reference standard.

Methods

Fifty-three subjects were included and divided over three groups based on radiographic and clinical knee OA: 20 subjects with no OA (Kellgren-Lawrence grade (KLG) 0), 18 with mild OA (KLG2), and 15 with moderate OA (KLG3). All patients underwent a 5-min qDESS scan. We measured T2 relaxation times in four cartilage and four meniscus regions of interest (ROIs) and performed structural OA evaluation with the MRI Osteoarthritis Knee Score (MOAKS) using qDESS with multiplanar reformatting. Between-group differences in T2 values and MOAKS were calculated using ANOVA. Correlations of the reference standard (i.e., radiographic knee OA) with T2 and MOAKS were assessed with correlation analyses for ordinal variables.

Results

In cartilage, mean T2 values were 36.1 ± SD 4.3, 40.6 ± 5.9, and 47.1 ± 4.3 ms for no, mild, and moderate OA, respectively (p < 0.001). In menisci, mean T2 values were 15 ± 3.6, 17.5 ± 3.8, and 20.6 ± 4.7 ms for no, mild, and moderate OA, respectively (p < 0.001). Statistically significant correlations were found between radiographic OA and T2 and between radiographic OA and MOAKS in all ROIs (p < 0.05).

Conclusion

Quantitative T2 and structural assessment of cartilage and meniscus, using a single 5-min qDESS scan, can distinguish between different grades of radiographic OA, demonstrating the potential of qDESS as an efficient tool for OA imaging.

Key Points

• Quantitative T
2
values of cartilage and meniscus as well as structural assessment of the knee with a single 5-min quantitative double-echo steady-state (qDESS) scan can distinguish between different grades of knee osteoarthritis (OA).

• Quantitative and structural qDESS-based measurements correlate significantly with the reference standard, radiographic degree of OA, for all cartilage and meniscus regions.

• By providing quantitative measurements and diagnostic image quality in one rapid MRI scan, qDESS has great potential for application in large-scale clinical trials in knee OA.
Pre- and intraoperative acoustic and functional assessment of the novel APrevent® VOIS implant during routine medialization thyroplasty
Authors: Ho Guan-Yuh , Leonhard Matthias , Denk-Linnert Doris-Maria , Schneider-Stickler Berit
Published: December 2019

Purpose

Persistent unilateral vocal fold paralysis (UFVP) with glottal insufficiency often requires type I medialization thyroplasty (MT). Previous implants cannot be adjusted postoperatively if necessary. The newly developed APrevent®VOIS implant (VOIS) can provide postoperative re-adjustment to avoid revision MT. The objective of this pilot study is to evaluate the VOIS intraoperatively concerning voice improvement, surgical feasibility and device handling.

Methods

During routine MT, VOIS was applied short time in eight patients before the regular implantation of the Titanium Vocal Fold Medialization Implant (TVFMI™). In all patients, perceptual voice sound analysis using R(oughness)–B(reathiness)–H(oarseness)-scale, measurement of M(aximum)–P(honation)–T(ime) and glottal closure in videolaryngoscopy were performed before and after implanting VOIS/TVFMI™. Acoustic analyses of voice recordings were performed using freeware praat. Surgical feasibility, operative handling and device fitting of VOIS and TVFMI™ were assessed by the surgeon using V(isual)-A(nalog)-S(cale). Data were statistically analyzed with pairedttest.

Result

All patients showed significant improvement of voice sound parameters after VOIS/TVFMI™ implantation. The mean RBH-scale improved from preoperativeR = 2.1,B = 2.3,H = 2.5 toR = 0.6,B = 0.3,H = 0.8 after VOIS andR = 0.5,B = 0.3,H = 0.8 after TVFMI™ implantation. The mean MPT increased from preoperative 7.9 to 14.6 s after VOIS and 13.8 s after TVFMI™ implantation. VOIS/TVFMI™ achieved complete glottal closure in 7/8 patients. The satisfaction with intraoperative device fitting and device handling of VOIS was as good as that of TVFMI™.

Conclusion

The novel APrevent®VOIS implant showed similar intraoperative voice improvement compared to routinely used TVFMI™ without adverse device events and with safe device fitting.
Current practices in children with severe acute asthma across European PICUs: an ESPNIC survey
Authors: Boeschoten Shelley , de Hoog Matthijs , Kneyber Martin , Merkus Peter , Boehmer Annemie , Buysse Corinne
Published: December 2019

Most pediatric asthma guidelines offer evidence-based or best practice approaches to the management of asthma exacerbations but struggle with evidence-based approaches for severe acute asthma (SAA). We aimed to investigate current practices in children with SAA admitted to European pediatric intensive care units (PICUs), in particular, adjunct therapies, use of an asthma severity score, and availability of a SAA guideline. We designed a cross-sectional electronic survey across European PICUs. Thirty-seven PICUs from 11 European countries responded. In 8 PICUs (22%), a guideline for SAA management was unavailable. Inhaled beta-agonists and anticholinergics, combined with systemic steroids and IV MgSO4was central in SAA treatment. Seven PICUs (30%) used a loading dose of a short-acting beta-agonist. Eighteen PICUs (49%) used an asthma severity score, with 8 different scores applied. Seventeen PICUs (46%) observed an increasing trend in SAA admissions.

Conclusion: Variations in the treatment of children with SAA mainly existed in the use of adjunct therapies and asthma severity scores. Importantly, in 22% of the PICUs, a SAA guideline was unavailable. Standardizing SAA guidelines across PICUs in Europe may improve quality of care. However, the limited number of PICUs represented and the data compilation method are constraining our findings.What is Known:•Recent reports demonstrate increasing numbers of children with SAA requiring PICU admission in several countries across the world.•Most pediatric guidelines offer evidence-based approaches to the management of asthma exacerbations, but struggle with evidence-based approaches for SAA beyond these initial steps.What is New:•A large arsenal of adjunct therapies and 8 different asthma scores were used.•In a large number of PICUs, a written guideline for SAA management is lacking.
Energy and protein requirements for children with CKD stages 2-5 and on dialysis–clinical practice recommendations from the Pediatric Renal Nutrition Taskforce
Authors: Shaw Vanessa , Polderman Nonnie , Renken-Terhaerdt José , Paglialonga Fabio , Oosterveld Michiel , Tuokkola Jetta , Anderson Caroline , Desloovere An , Greenbaum Laurence , Haffner Dieter , Nelms Christina , Qizalbash Leila , Vande Walle Johan , Warady Bradley , Shroff Rukshana , Rees Lesley
Published: December 2019

Dietary management in pediatric chronic kidney disease (CKD) is an area fraught with uncertainties and wide variations in practice. Even in tertiary pediatric nephrology centers, expert dietetic input is often lacking. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, was established to develop clinical practice recommendations (CPRs) to address these challenges and to serve as a resource for nutritional care. We present CPRs for energy and protein requirements for children with CKD stages 2–5 and those on dialysis (CKD2–5D). We address energy requirements in the context of poor growth, obesity, and different levels of physical activity, together with the additional protein needs to compensate for dialysate losses. We describe how to achieve the dietary prescription for energy and protein using breastmilk, formulas, food, and dietary supplements, which can be incorporated into everyday practice. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgment. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.
Long-term all-cause mortality and cardiovascular outcomes in Scottish children after initiation of renal replacement therapy: a national cohort study
Authors: Galiyeva Dinara B. , Jackson Caroline A. , Wild Sarah H. , Burns Susan , Hughes David , Traynor Jamie P. , Metcalfe Wendy , Halbesma Nynke
Published: December 2019

Background

Data on long-term outcomes in children who have received renal replacement therapy (RRT) for end-stage renal disease are limited.

Methods

We studied long-term survival and incidence of fatal and nonfatal cardiovascular disease (CVD) events and determinants of these outcomes in children who initiated RRT between 1961 and 2013 using data from the Scottish Renal Registry (SRR). Linkage to morbidity records was available from 1981.

Results

A total of 477 children of whom 55% were boys, almost 50% had congenital urinary tract disease (CAKUT), 10% received a transplant as the first mode of RRT and almost 60% were over 11 years of age at start of RRT were followed for a median of 17.8 years (interquartile range (IQR) 8.7–26.6 years). Survival was 87.3% (95% confidence interval (CI) 84.0–90.1) at 10 years and 77.6% (95% CI 73.3–81.7) at 20 years. During a median follow-up of 14.96 years (IQR 7.1–22.9), 20.9% of the 381 patients with morbidity data available had an incident of CVD event. Age < 2 years at start of RRT, receiving dialysis rather than a kidney transplant and primary renal disease (PRD) other than CAKUT or glomerulonephritis (GN), were associated with a higher risk of all-cause mortality. Male sex, receiving dialysis rather than a kidney transplant and PRD other than CAKUT or GN, was associated with a higher risk of CVD incidence.

Conclusions

Mortality and CVD incidence among children receiving RRT are high. PRD and RRT modality were associated with increased risk of both all-cause mortality and CVD incidence.
Influence of mild-moderate hypocapnia on intracranial pressure slow waves activity in TBI
Authors: Beqiri Erta , Czosnyka Marek , Lalou Afroditi D. , Zeiler Frederick A. , Fedriga Marta , Steiner Luzius A. , Chieregato Arturo , Smielewski Peter
Published: December 2019

Background

In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005–0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge.

Methods

ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15–20% increase in respiratory minute volume) was performed as part of a clinical CO2-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005–0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP).

Results

Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001).

Conclusion

In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.
Soil Microbial Responses to 28 Years of Nutrient Fertilization in a Subarctic Heath
Authors: Hicks Lettice C. , Rousk Kathrin , Rinnan Riikka , Rousk Johannes
Published: December 2019

Arctic and subarctic soils are typically characterized by low nitrogen (N) availability, suggesting N-limitation of plants and soil microorganisms. Climate warming will stimulate the decomposition of organic matter, resulting in an increase in soil nutrient availability. However, it remains unclear how soil microorganisms in N-limited soils will respond, as the direct effect of inorganic N addition is often shown to inhibit microbial activity, while elevated N availability may have a positive effect on microorganisms indirectly, due to a stimulation of plant productivity. Here we used soils from a long-term fertilization experiment in the Subarctic (28 years at the time of sampling) to investigate the net effects of chronic N-fertilization (100 kg N ha−1 y−1, added together with 26 kg P and 90 kg K ha−1 y−1, as expected secondary limiting nutrients for plants) on microbial growth, soil C and N mineralization, microbial biomass, and community structure. Despite high levels of long-term fertilization, which significantly increased primary production, we observed relatively minor effects on soil microbial activity. Bacterial growth exhibited the most pronounced response to long-term fertilization, with higher rates of growth in fertilized soils, whereas fungal growth remained unaffected. Rates of basal soil C and N mineralization were only marginally higher in fertilized soils, whereas fertilization had no significant effect on microbial biomass or microbial community structure. Overall, these findings suggest that microbial responses to long-term fertilization in these subarctic tundra soils were driven by an increased flow of labile plant-derived C due to stimulated plant productivity, rather than by direct fertilization effects on the microbial community or changes in soil physiochemistry.
MRI compared with low-dose CT scanning in the diagnosis of axial spondyloarthritis
Authors: Ye Lusi , Liu Yuncai , Xiao Qinqin , Dong Ledan , Wen Caiyun , Zhang Zhang , Jin Mengmeng , Brown Matthew A. , Chen Dan
Published: December 2019

Objectives

To compare the performance of conventional radiography, ldCT, and MRI in the diagnosis of sacroiliitis in suspected axial spondyloarthritis (axSpA).

Methods

Patients presenting with > 3 months chronic back pain were assessed by axSpA-experienced rheumatologists and diagnosed as axSpA or not; axSpA patients were then considered nr-axSpA or AS using plain radiography. Non-axSpA patients were recruited as controls, and divided into non-inflammatory and inflammatory groups on the basis of inflammatory back pain and/or CRP/ESR elevation. Clinical variables, pelvic radiography, sacroiliac joint (SIJ) ldCT, and SIJ MRI were obtained.

Results

A total of 121 patients were included and had SIJ radiography and ldCT, of whom 71 additionally had an SIJ MRI. These included 23 non-inflammatory controls, 21 inflammatory controls, 32 nr-axSpA cases, and 45 AS cases. Fourteen of 32 (44%) nr-axSpA patients had positive ldCT scans, 21/24 (88%) had MRI-BMO, and 11/24 (46%) had MRI-structural lesions. ldCT had high specificity with only 1/23 (4%) non-inflammatory controls being positive. MRI-BMO had the highest sensitivity for nr-axSpA, but compared with ldCT lower specificity, with 5/15 (33%) of non-inflammatory controls being positive, and similar sensitivity for AS (20/22 (91%) vs 44/44 for ldCT).

Conclusions

ldCT identifies evidence of radiographic change in a significant proportion of nr-axSpA cases and is highly specific for axSpA. MRI-BMO lesions are more sensitive than either conventional radiography or MRI-structural assessment for axSpA. The relative position of these imaging modalities in screening for axSpA needs to be reconsidered, also taking into account the costs involved.Key Points• ldCT is more sensitive for erosions or sclerosis in axSpA than plain radiography, with 44% of patients with nr-axSpA having evidence of AS-related sacroiliac joint changes on ldCT.• MRI-structural lesions are no more sensitive but are less specific for AS than ldCT.• MRI-BMO is the most sensitive test for nr-axSpA of the modalities tested but is less specific for axSpA than for ldCT.
The knowledge level of rheumatoid arthritis patients about their disease in a developing country. A study in 168 Bangladeshi RA patients
Authors: Kamruzzaman A. K. M. , Chowdhury Minhaj Rahim , Islam Md Nazrul , Sultan Imtiaz , Ahmed Shamim , Shahin Abu , Alam Mohammad Mahbubul , Azad Md. Ak , Hassan M. Masudul , Amin Md Zahid , Sinha Sudeshna , Ahmad Habib Imtiaz , Shazzad Md Nahiduzzamane , Ahmad Sonia Nasreen , Haq Syed Atiqul , Rasker Johannes Jacobus
Published: December 2019

Objectives

To assess disease-related knowledge of rheumatoid arthritis (RA) patients

Patients and methods

Consecutive RA patients were invited from the rheumatology departments of BSMM University, Dhaka, Bangladesh. The Bangla version of the Patient Knowledge Questionnaire (B-PKQ) was used. Correlations between the B-PKQ scores and clinical-demographic data were measured using Pearson’s correlation coefficient. Impact of independent variables on the level of knowledge about RA was analyzed through multiple regression analysis. Possible explanatory variables included the following: age, disease duration, formal education level, and Bangla Health Assessment Questionnaire (B-HAQ) score. Analysis of variance (ANOVA) was used to test the difference between demographical, clinical, and socioeconomic variables. For statistical analysis, SPSS statistics version 20 was used.

Results

A total of 168 RA patients could be included. The mean B-PKQ score was 9.84 (range 1–20) from a possible maximum of 30. The mean time for answering the questionnaire was 24.3 min (range 15–34). Low scores were observed in all domains but the lowest were in medications and joint protection/energy conservation. Knowledge level was higher (15.5) in 6 patients who had RA education before enrollment. B-PKQ showed positive correlation with education level (r = 0.338) and negative correlation with HAQ (r = −0.169). The B-PKQ showed no correlation with age, disease duration, having first degree family member with RA, education from other sources (neighbor, RA patient, nurses), or information from mass media.

Conclusions

Disease-related knowledge of Bangladeshi RA patients was poor in all domains. Using these findings, improved education and knowledge will result in better disease control.Key Points• Little is known about the knowledge of RA patients regarding their disease and its treatment in Bangladesh and in developing countries in general.• We found that the knowledge of Bangladeshi RA patients regarding their disease was poor in all domains; it correlated positive with education level and negative with function (HAQ), but showed no correlation with age or disease duration.• The findings of this study can be used for improving current patient education programs by health professionals and through mass media.• Better disease control of RA may be achieved by improving patient knowledge in a developing country like Bangladesh, but also in other parts of the world.
Dotinurad: a novel selective urate reabsorption inhibitor as a future therapeutic option for hyperuricemia
Authors: Kuriyama Satoru
Published: December 2019

Gout is a chronic inflammatory disease caused by precipitation of urate crystals in the joints, kidneys, and urinary tract. Independent of urate deposition disorders, recent studies have shown a positive association between circulating uric acid (UA) levels and cardiovascular (CV) diseases. These results indicate that UA is a precipitating factor of both gout and the progression of CV diseases, including hypertension and/or chronic kidney disease (CKD). A large body of evidence has shown that UA-lowering therapies are effective in preventing the progression of hypertension/CKD and that a causal relationship exists between serum UA level and CV diseases. Despite the urgent need for effective UA-lowering drugs that can be used to obtain better therapeutic outcomes and prognosis, only few drugs have been developed in the past decades. Recently, febuxostat and topiroxostat, which are xanthine oxidoreductase inhibitors, were developed and used in clinical practice. Of note, after the approval of lesinurad, which is a urate transporter-1 (URAT-1) inhibitor, in the United States in 2015, dotinurad (Fig. 1), a novel promising drug with selective UA reabsorption inhibitory property, was recently developed in Japan in 2018. Dotinurad is indicated for patients with hyperuricemia/gout as most patients with hyperuricemia are classified into “underexcretion type”, which requires the inhibition of URAT-1 to excrete excess UA via the kidney. Focusing on dotinurad, the present study highlighted the multifaceted preliminary new trials that assessed for drug efficacy and safety, pharmacokinetics (PK) according to age and gender, the presence or absence of liver and kidney disorders, drug interactions with NSAID, and non-inferiority of dotinurad to either febuxostat or benzbromarone. A series of studies included in this supplemental review indicate that dotinurad reduces serum UA levels, and its efficacy and safety are similar to those of other UA-lowering agents currently used even in hyperuricemic patients with various clinical conditions. Moreover, two exploratory studies with a small sample size were conducted to compare PK parameters between patients with overproduction- and underexcretion-type hyperuricemia, and results showed that the effects of UA-lowering agents were comparable between the two subtype groups.
A minimal-variable symplectic method for isospectral flows
Authors: Viviani Milo
Published: December 2019

Isospectral flows are abundant in mathematical physics; the rigid body, the the Toda lattice, the Brockett flow, the Heisenberg spin chain, and point vortex dynamics, to mention but a few. Their connection on the one hand with integrable systems and, on the other, with Lie–Poisson systems motivates the research for optimal numerical schemes to solve them. Several works about numerical methods to integrate isospectral flows have produced a large varieties of solutions to this problem. However, many of these algorithms are not intrinsically defined in the space where the equations take place and/or rely on computationally heavy transformations. In the literature, only few examples of numerical methods avoiding these issues are known, for instance, the spherical midpoint method on $${{\mathfrak {s}}}{{\mathfrak {o}}}(3)$$

s
o
(
3
)

. In this paper we introduce a new minimal-variable, second order, numerical integrator for isospectral flows intrinsically defined on quadratic Lie algebras and symmetric matrices. The algorithm is isospectral for general isospectral flows and Lie–Poisson preserving when the isospectral flow is Hamiltonian. The simplicity of the scheme, together with its structure-preserving properties, makes it a competitive alternative to those already present in literature.
The Synthesis of Hydrobenzoin-Based Monoaza Crown Ethers and Their Application as Recyclable Enantioselective Catalysts
Authors: Nemcsok Tamás , Rapi Zsolt , Bagi Péter , Oláh Attila , Keglevich György , Bakó Péter
Published: December 2019

New recyclable monoaza-15-crown ethers have been synthesized starting from (R,R)-(+)- and (S,S)-(−)-hydrobenzoin. These macrocycles proved to be efficient and reusable phase transfer catalysts in a few asymmetric reactions under mild conditions. The asymmetric epoxidation of trans-chalcone took place with up to 81% ee, while using other chalcone derivatives, the products were formed with 68–88% ee. The hydrobenzoin-based lariat ethers were also tested in the cyclopropanation of a few electron deficient olefins using diethyl bromomalonate to afford the product with good enantioselectivities (54–75% ee). The catalysts were recovered by salt formation, followed by extraction, and were reused without the loss of the activity and effect on the enantioselectivity.

Graphic Abstract

The synthesis of hydrobenzoin-based monaza crown ethers and their application as recyclable enantioselective catalysts.
Protecting Consumer Protection Values in the Fourth Industrial Revolution
Authors: Howells G.
Published: December 2019

We are entering into an era of new technological possibilities. Many benefits will be derived for consumers from the development of data and computer-driven innovation. We will have new products and services and new ways of making and supplying goods and services.Without wanting to inhibit innovation, this article calls for the legal system to remain committed to an ideology and legal framework that supports consumer protection. It will counsel against assuming that the law should give way unduly to the technology agenda, whilst accepting that adaptations should be made and also that there should be a critical review of whether traditional forms of regulation are needed in the Fourth Industrial Age.
The horofunction boundary of the infinite dimensional hyperbolic space
Authors: Claassens Floris
Published: December 2019

In this paper we give a complete description of the horofunction boundary of the infinite dimensional real hyperbolic space, and characterise its Busemann points.
Mapping of QTLs for source and sink associated traits under elevated CO2 in rice (Oryza sativa L.)
Authors: Dai Li-Ping , Lu Xue-Li , Zou Wei-Wei , Wang Chang-Jian , Shen Lan , Hu Jiang , Zhang Guang-Heng , Ren De-Yong , Chen Guang , Zhang Qiang , Xue Da-Wei , Dong Guo-Jun , Gao Zhen-Yu , Guo Long-Biao , Zhu Li , Mou Tong-Min , Qian Qian , Zeng Da-Li
Published: December 2019

Rice source- and sink-associated traits are important for grain yield and are sensitive to environmental conditions. The continuing increase of CO2 concentrations in the atmosphere will become a major challenge for rice growth and development in the future due to changes in our climate such as extremes in temperature. To guarantee food safety, novel genetic loci need to be identified for source- and sink-associated traits that are specifically expressed under elevated CO2 conditions. Eighty chromosome segment substitution lines carrying japonica (Nipponbare) chromosome segments in the indica (9311) background were used in this study. QTL analysis was conducted for source- and sink-related traits, including flag leaf length, flag leaf width, flag leaf fresh weight, flag leaf dry weight, primary branch number, secondary branch number, grain number per panicle, panicle weight per plant, chlorophyll a, chlorophyll b, and carotenoid contents, under ambient CO2 concentrations and free-air CO2 enrichment. A total of 49 QTLs for these traits were detected on chromosomes 1, 3, 5, 6, 7, 9, and 12 under the two conditions; the variance explained by these QTLs varied from 6.22 to 38.15%. Among these QTLs, 19 of them were detected under the natural field conditions and 30 were detected in the elevated CO2 conditions. In addition, 2 and 13 QTLs were specifically expressed in the natural and CO2-enriched conditions, respectively. Our findings have important implications on the utilization of germplasm resources for ensuring food security under elevated CO2 levels, especially for QTLs that were specifically detected under the elevated CO2 condition.
Comparison of Parent Questionnaires, Examiner-Led Assessment and Parents’ Concerns at 14 Months of Age as Indicators of Later Diagnosis of Autism
Authors:   The BASIS Team, Pasco Greg , Davies Kim , Ribeiro Helena , Tucker Leslie , Allison Carrie , Baron-Cohen Simon , Johnson Mark H. , Charman Tony
Published: December 2019

Parents participating in a prospective longitudinal study of infants with older siblings with autism completed an autism screening questionnaire and were asked about any concerns relating to their child’s development, and children were administered an interactive assessment conducted by a researcher at 14 months. Scores on the parent questionnaire were highest for children later diagnosed with autism. Parental concerns and scores from the examiner-led assessment distinguished children with later developmental difficulties (both autism and other developmental atypicalities) from those who were developing typically. Children about whom parents expressed concern scored higher on both the questionnaire and the interactive assessment than those without concerns. There were no significant associations between total or individual item scores from the questionnaire and interactive assessment.
Reliable workflow for inversion of seismic receiver function and surface wave dispersion data: a “13 BB Star” case study
Authors: Chrapkiewicz Kajetan , Wilde-Piórko Monika , Polkowski Marcin , Grad Marek
Published: December 2019

Non-linear inverse problems arising in seismology are usually addressed either by linearization or by Monte Carlo methods. Neither approach is flawless. The former needs an accurate starting model; the latter is computationally intensive. Both require careful tuning of inversion parameters. An additional challenge is posed by joint inversion of data of different sensitivities and noise levels such as receiver functions and surface wave dispersion curves. We propose a generic workflow that combines advantages of both methods by endowing the linearized approach with an ensemble of homogeneous starting models. It successfully addresses several fundamental issues inherent in a wide range of inverse problems, such as trapping by local minima, exploitation of a priori knowledge, choice of a model depth, proper weighting of data sets characterized by different uncertainties, and credibility of final models. Some of them are tackled with the aid of novel 1D checkerboard tests—an intuitive and feasible addition to the resolution matrix. We applied our workflow to study the south-western margin of the East European Craton. Rayleigh wave phase velocity dispersion and P-wave receiver function data were gathered in the passive seismic experiment “13 BB Star” (2013–2016) in the area of the crust recognized by previous borehole and refraction surveys. Final models of S-wave velocity down to 300 km depth beneath the array are characterized by proximity in the parameter space and very good data fit. The maximum value in the mantle is higher by 0.1–0.2 km/s than reported for other cratons.