bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbleeds colocalize with enlarged juxtacortical perivascular spaces in amnestic mild cognitive impairment and early Alzheimer’s disease: A 7 Tesla MRI study
Authors: Bouvy Willem H , van Veluw Susanne J , Kuijf Hugo J , Zwanenburg Jaco JM , Kappelle Jaap L , Luijten Peter R , Koek Huiberdina L , Geerlings Mirjam I , Biessels Geert J ,   On behalf of the Utrecht Vascular Cognitive Impairment (VCI) Study Group
Published: March 2019

MRI-visible perivascular spaces (PVS) in the semioval centre are associated with cerebral amyloid angiopathy (CAA), but it is unknown if PVS co-localize with MRI markers of CAA. To examine this, we assessed the topographical association between cortical cerebral microbleeds (CMBs) – as an indirect marker of CAA – and dilatation of juxtacortical perivascular spaces (jPVS) in 46 patients with amnestic mild cognitive impairment (aMCI) or early Alzheimer’s disease (eAD). The degree of dilatation of jPVS <1 cm around each cortical CMBs was compared with a similar reference site (no CMB) in the contralateral hemisphere, using a 4-point scale. Also, jPVS dilatation was compared between patients with and without cortical CMBs. Eleven patients (24%) had cortical CMBs [total=35, median=1, range=1–14] of whom five had >1 cortical CMBs. The degree of jPVS dilatation was higher around CMBs than at the reference sites [Wilcoxon signed rank test, Z = 2.2, p = 0.03]. Patients with >1 cortical CMBs had a higher degree of jPVS dilation [median=2.2, IQR = 1.8–2.3] than patients without cortical CMBs [median=1.4, IQR = 1.0–1.8], p = 0.02. We found a topographical association between a high degree of jPVS dilatation and cortical CMBs, supporting a common underlying pathophysiology – most likely CAA.
Towards a new paradigm of global development? Beyond the limits of international development
Authors: Horner Rory
Published: March 2019

An international development framing is increasingly ill-fitting to a 21st century characterized by interconnected globalized capitalism, the challenge of sustainable development, as well as the blurring of North–South boundaries. While the term global development is increasingly employed, and appears more suited, it is used with different implicit meanings and is often conflated with international development. This article explores the potential of an emerging paradigm of global development as applicable to the whole world. A relational global development approach is advocated here, acknowledging the need for critical attention to the enduring tensions between universalization and geographic variation.
Modeling economic and epidemiological impact of voluntary medical male circumcision among men who have sex with men in Beijing, China
Authors: Zhang Chen , Penson David F , Qian Han-Zhu , Webb Glenn F , Lou Jie , Shephard Brian E , Liu Yu , Vermund Sten H
Published: March 2019

Voluntary medical male circumcision (VMMC) among men who have sex with men (MSM) may protect against HIV acquisition. We conducted a series of analyses to assess if expanded VMMC might reduce HIV incidence among MSM effectively and economically. We used a deterministic compartmental model to project new HIV cases (2016–2026) under annual VMMC coverage rates (λ) ranging from 0.0001 to 0.15. The ‘number needed to avert’ (NNA) is defined as the cumulative number of VMMCs conducted up to that year divided by the cumulative number of HIV cases averted in that specific year. Compared with the baseline circumcision coverage rate, we projected that new HIV cases would be reduced with increasing coverage. By 2026 (last year simulated), the model generated the lowest ratio (11.10) when the annual circumcision rate was the most optimistic (λ = 0.15). The breakeven point was observed at the year of 2019 with the annual VMMC coverage rate of 0.001. The total cost saved by averting HIV cases would range from 2.5 to 811 million US dollars by the end of 2026 with different hypothetical coverage rates. Our model suggests that acceleration in VMMC implementation among MSM could help stem the HIV/AIDS epidemic.
Reliance and representations/promises in frozen embryo disputes: UK and Israeli approaches to estoppel
Authors: Chrysanthou Alexander
Published: March 2019

Frozen embryo disputes are hard cases since providing the decision over whether or not to become a parent/dispose of the embryo(s) to one gamete provider in the way he/she wishes denies the other an equivalent decision. In response, estoppel, it is argued, can provide a doctrinally robust response due to its flexibility in deeming whether a person relied upon representation(s) or promise(s) made. The exploration of this theme indicates that the gamete provider seeking implantation will often have a stronger case in equity, than via other legal avenues. The different approaches in UK and Israeli law in this context are duly examined.
Taxis for neoliberalism! Surveillance and resistance in post-industrial Philadelphia
Authors: Geesin Beverly , Mollan Simon
Published: March 2019

As a consequence of neoliberalism, employment has become increasingly precarious and informal, sitting outside of traditional organizational contexts. There is a need to better understand how these structures emerge and, importantly, how workers can also adapt to challenge these shifts. This article is a study of a labour dispute between Philadelphia taxicab drivers and the governmental regulatory body. The dispute was centred around the implementation of surveillance technologies to regulate and control the industry and the drivers’ working practices which they considered to be de-professionalizing and an infringement of their liberty. The drivers resisted through traditional organizing, legal challenges and creating unconventional alliances. We argue that this labour dispute should be seen in the wider context of how a neoliberal political economy emerges and is maintained – in this case not by capital, but by the state. The article is a longitudinal case study covering the period from 2004 to 2011. As such, it is a prologue to later technologically driven transformations in the taxicab industry (such as ride-hailing apps) that have further exacerbated precarity among the workforce.
Evaluating monitoring, evaluation and learning initiatives in the New Zealand and Australian agricultural research and innovation systems: The MEL2 framework
Authors: Stone-Jovicich Samantha , Percy Helen , McMillan Larelle , Turner James A , Chen Lan , White Toni
Published: March 2019

The potential for monitoring, evaluation and learning (MEL) to enhance innovation and impact in agricultural research and development is receiving increasing attention. New Zealand’s AgResearch Limited and Australia’s CSIRO Agriculture and Food are working with their scientists to support the organisations to achieve greater innovation and impact by embedding MEL into research programs and projects. However, both organisations have found it challenging to systematically demonstrate the value of their MEL initiatives. While there is an increasing number of case studies and anecdotes pointing towards the contribution of MEL to fostering innovation that delivers social, economic and environmental impacts, there is limited evidence, collated through systematic and rigorous methods, to substantiate this. This article presents an evaluation framework drawing on insights from complexity science (the Cynefin framework), evaluation practice and research (complexity-aware M&E and reflective practice) and innovation capacities (learning, reflection and adaptation). The framework is intended for research organisations working in agricultural innovation systems to be able to demonstrate the value of their MEL initiatives as well as carry out comparative analyses. It also supports organisational learning to better inform evaluative strategies and actions.
Needs, strain, coping, and mental health among caregivers of individuals with autism spectrum disorder: A moderated mediation analysis
Authors: Lee Gloria K , Krizova Katarina , Shivers Carolyn M
Published: March 2019

This study investigated the relationships among caregiving strain, coping, and mental health among caregivers of individuals with autism spectrum disorder (ASD) and the mediational moderation of caregiver needs. One hundred and ninety-three caregivers of individuals with ASD completed an online survey. Results showed that maladaptive coping behaviors were significant in mediating the relationship between strain and mental health. Professional service and emotional caregiving needs moderated the relationship between maladaptive coping and mental health at times of high caregiving strain, but not involvement, health information, and instrumental support needs. Results highlighted the negative effect of maladaptive coping, as well as professional service and emotional support needs were salient in moderating coping and mental health in times of high caregiving strain.
China’s livestreaming industry: platforms, politics, and precarity
Authors: Cunningham Stuart , Craig David , Lv Junyi
Published: March 2019

This article examines conditions placing China’s livestreamers as central focal points in the increasing tensions between the cultural politics and economic ambitions of digital China. Framed by concerns around ‘platformization’, this research uses a creator-centric critical media industries studies perspective. Chinese livestreamers enjoy a greater degree of opportunity than their Western counterparts, including competing gameplay platforms that vie for premier gameplayers who can dictate their own terms. Decades-old cultural policies fostered underlying conditions that advantage female streamers engaging in gendered performativity to appeal to lonely rich men. Livestreamers ride marketing imperatives directing consumers to cross-integrated e-commerce platforms that fuel China’s emerging consumption culture. But livestreamers engage in ‘edge ball’ violations of Chinese norms that make them subject to an ever-increasing level of state regulatory restraint, signaling the return of ideology designed to mold online expression and behavior.
Design suggestions for greater teamwork, communication and security in hospital emergency departments
Authors: Gharaveis Arsalan , Kirk Hamilton D. , Shepley Mardelle , Pati Debajyoti , Rodiek Susan
Published: March 2019

This paper presents design recommendations based on a qualitative study for enhancement of teamwork, communication and security in emergency departments. Considering the crucial role of the emergency department in providing urgent care, the design of physical environments to facilitate immediate, efficient and effective patient care are of significant importance. The study adopted an exploratory approach, where levels of visibility, teamwork, communication and security were explored in five emergency departments using one-on-one interviews. Data collection and analysis involved interviews with medical staff and a textual analysis of interview transcripts. The study findings support the view that teamwork, communication and security can be improved by the physical layout in an emergency department, as well as other environmental factors including acoustics, lighting, accessibility of supplies, entrance control and privacy. The study provides tangible design guidelines for architects, healthcare planners and emergency department managers to support design decisions and strategies that promote emergency department effectiveness.
Online prediction and control method for compensation regulation value in grinding processes
Authors: Zheng Peng , Liu Dong-liang , Tian Xue-hao , Zhi Zhan-xin , Zhang Lin-na
Published: March 2019

In any grinding process, compensation regulation value is a crucial factor for maintaining precision during the batch processing of workpieces. Geometric characteristics, buffing allowance, temperature, wheel speed, and workpiece speed are the main factors that affect compensation regulation value in any grinding process. In this article, a novel prediction method for compensation regulation value is proposed based on incremental support vector machine and mixed kernel function. The support vectors for the prediction model are extracted using the convex hull vertex optimization algorithm, and the speed of the operation can be increased effectively. In addition, the parameters of the model are optimized using cross-validation optimization method to improve the accuracy of the prediction model. Then, the feedback control strategy of compensation regulation value for the grinding process is also proposed. Single-factor and multi-factor experiments are implemented respectively using the proposed method. The results verify the feasibility and effectiveness of the proposed method. It is also noted that the machining accuracy is improved significantly in comparison with the machining without prediction and compensation control. Moreover, by applying the prediction compensation control of compensation regulation value to the active measurement and control of the grinding process, a feedback system is formed, and then the intelligentization of the grinding system can be realized.
External validation of CLI Frailty Index and assessment of predictive value of modified CLI Frailty Index for patients with critical limb ischemia undergoing infrainguinal revascularization
Authors: Morisaki Koichi , Furuyama Tadashi , Matsubara Yutaka , Inoue Kentaro , Kurose Shun , Yoshino Shinichiro , Nakayama Ken , Yamashita Sho , Yoshiya Keiji , Yoshiga Ryosuke , Maehara Yoshihiko
Published: March 2019

Objectives

CLI Frailty is a useful diagnostic criterion of frailty in patients with critical limb ischemia (CLI). It is important to evaluate not only comorbidities but also frailty in decision making to select the type of treatment for CLI patients. The purposes of our study were to externally validate the CLI Frailty Index and to evaluate the modified CLI Frailty Index by measurement of skeletal muscle mass using computed tomography.

Methods

Patients who underwent preoperative computed tomography examination and infrainguinal revascularization between 2002 and 2015 were retrospectively analyzed. A patient was defined as CLI Frailty (+), if two or more of the following criteria were present: low Geriatric Nutritional Risk Index (GNRI), low skeletal muscle mass index (SMI) evaluated by prediction equations, and non-ambulatory status. For the modified CLI Frailty Index, skeletal muscle area was measured by computed tomography instead of prediction equations.

Results

During the study period, 226 patients with CLI underwent revascularization; we included 127 patients and excluded 99 patients who were treated only with iliac revascularization or did not undergo CT scans. The overall survival at two years after revascularization was 83.6% for the CLI Frailty (−) group versus 63.2% for the CLI Frailty (+) group ( P = .02). The overall survival at two years after revascularization was 89.7% for the modified CLI Frailty (−) group versus 60.5% for the modified CLI Frailty (+) group ( P < .01). Multivariate analysis 1 including CLI Frailty revealed that hemodialysis (HR, 3.71; 95% CI, 1.58–8.83; P < .01), CLI Frailty (HR, 3.22; 95% CI, 1.35–7.47; P < .01) and cerebrovascular disease (HR, 2.58; 95% CI, 1.09–5.91; P = .03) were risk factors for overall survival two years after revascularization. In multivariate analysis 2 including modified CLI Frailty, modified CLI Frailty (HR, 5.92; 95% CI, 2.49–15.7; P < .01), hemodialysis (HR, 4.03; 95% CI, 1.65–10.0; P < .01) and diabetes mellitus (HR, 0.41; 95% CI, 0.16–0.99; P = .05) were risk factors for overall survival two years after revascularization.

Conclusions

Both the CLI Frailty and the modified CLI Frailty Indexes were useful in predicting the two-year overall survival of patients with CLI after infrainguinal revascularization. Although the measurement of skeletal muscle mass using computed tomography may accurately predict two-year overall survival, SMI prediction is effective for patients with CLI who did not undergo preoperative CT.
A Comprehensive Systematic Review of the Association Between Airway Mucins and Chronic Rhinosinusitis
Authors: Kato Kosuke , Song Brian H. , Howe Carol L. , Chang Eugene H.
Published: March 2019

Objective

Airway mucins are the major constituents of mucus and one of the first lines of host defense against inhaled pathogens. However, aberrant expression of mucins is associated with mucus hypersecretion resulting in chronic nasal drainage, a common complaint from patients with chronic rhinosinusitis (CRS). Our goal in this systematic review was to determine (1) expression profiles, (2) regulatory mechanisms, and (3) the pathologic roles of mucins associated with CRS.

Methods

MEDLINE, Cochrane Library, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies focused on the role of mucins in CRS. Quality was assessed using the Cochrane Risk of Bias tool. The full text articles selected were then categorized into 3 study groups: (1) clinical, (2) animal, and (3) in vitro cultures. Data regarding study design, population/setting, methods, and bias were extracted and synthesized.

Results

Our initial search generated 392 titles/abstracts. After the primary review, 111 articles underwent secondary review. The final review included 53 articles, including 34 articles (64%) in the clinical study group, 3 articles (6%) in the animal study group, and 16 articles (30%) in the in vitro study group. In total, aberrant expression of 8 mucins—6 secreted-mucins (MUC2, -5AC, -5B, -6, -7, and -8) and 2 membrane-bound mucins (MUC1 and -4)—were identified in CRS tissues compared to healthy controls. Mucin expression was associated with bacterial sinusitis, inflammatory markers, and the response to steroid therapy in patients with CRS with nasal polyposis.

Conclusion

There is a strong correlation between alterations in mucin expression profiles and CRS. This systematic review highlights the most recent literature on the role of mucins in CRS. The analysis of these studies is limited by the heterogeneity in study designs, relatively few numbers of clinical samples, and lack of mechanistic studies in animal models and in vitro cultures.
Trends in educational mobility: How does China compare to Europe and the United States?
Authors: Gruijters Rob J , Chan Tak Wing , Ermisch John
Published: March 2019

Despite an impressive rise in school enrolment rates over the past few decades, there are concerns about growing inequality of educational opportunity in China. In this article, we examine the level and trend of educational mobility in China, and compare them to the situation in Germany, the Netherlands, the UK and the USA. Educational mobility is defined as the association between parents’ and children’s educational attainment. We show that China’s economic boom has been accompanied by a large decline in relative educational mobility chances, as measured by odds ratios. To elaborate, relative rates of educational mobility in China were, by international standards, quite high for those who grew up under state socialism. For the most recent cohorts, however, educational mobility rates have dropped to levels that are comparable to those of European countries, although they are still higher than the US level.
Plasma levels of pro-inflammatory molecules and their expressions are associated with severity of heart failure: An investigation in Chinese cohort
Authors: Xu Yongxi , Sun Hongyan , Wang Zhihao , Wang Yufeng
Published: March 2019

Heart failure (HF) is a syndrome with multiple clinical phenotypes affecting around 1%–2% of adult population worldwide, and about 230 million Chinese are affected by cardiovascular diseases. The important role of pro-inflammatory plasma cytokines with HF has been demonstrated in different populations. The aim of this study was to investigate importance of pro-inflammatory cytokines in Chinese HF patients. In all, 134 HF patients were enrolled in this study and further classified in to four clinical distinct groups according to New York Heart Association classification criteria (NYHA-I: n = 34, NYHA-II: n = 35, NYHA-III: n = 22 and NYHA-IV: n = 43). Sixty-eight healthy Chinese were enrolled as controls. Plasma levels of tumour necrosis factor-α (TNF-α), TNF-receptor 1 (TNFRI), TNF-receptor 2 (TNFRII), interleukin 6 (IL-6), soluble IL-6 receptor (sIL-6R), C-reactive protein (CRP), soluble cluster of differentiation 14 (sCD14) and interleukin 1 beta (IL-1β) were quantified by enzyme-linked immunosorbent assay (ELISA). Plasma levels of all parameters investigated in this study remained comparable among healthy controls and NYHA-I group. Plasma levels of TNF-α, TNFRI, TNFRII, IL-6, sIL-6R, CRP, sCD14 and IL-1β were significantly higher in NYHA-III and NYHA-IV clinical categories compared to other HF phenotype (NYHA-I and NYHA-II). Interestingly, TNFR-II levels were significantly higher in NYHA-II compared to NYHA-I. No significant difference of plasma sIL-6R was observed among various clinical categories. In conclusion, plasma levels of pro-inflammatory molecules are elevated in severe HF patients and may be used as possible biomarkers for accessing severity of HF.
Relationships between land use changes, stakeholders, and national scenic area administrations: A case study of Mount Jinfo and its surroundings in China
Authors: Du Wenwu , Penabaz-Wiley Sofia M , Kinoshita Isami
Published: March 2019

Rapid land use change in the surroundings of protected areas is rampant worldwide. This process is poorly understood and raises questions on how it happens, who shapes it, and the role of administration. To address these questions, we applied a case study in Jinfo National Scenic Area, China, and examined the relationships between land use change, concerned stakeholders, and the administration. Our study revealed that tourism-oriented commercial development and residential relocate were the main reasons for land use change and that the scenic area authorities, tourism enterprises, and locals were pivotal stakeholders in this process. In addition, we identified three authority types since the founding of Jinfo National Scenic Area. Evidence indicates that the conservation-oriented type and development-oriented type were less successful than the integration type in coordinating stakeholders and integrating the scenic area and its surroundings, and the development-oriented type has historically been most closely associated with damaging land use change. Further, we explored the causes for issues during the management of the Jinfo National Scenic Area included frequent administration changes, confusing plans and management goals, absence of a method for involving stakeholders, a lack of clear administrative authority, and a lack of an integrated national legal system. Our study highlights that it is critical to address these problems while aiming for a long-term balance of conservation and sustainable development in scenic areas and their surroundings.
Management of musculoskeletal foot and ankle conditions prior to public‐sector orthopaedic referral in South Australia
Authors: Walsh Tom P. , Ferris Linda R. , Cullen Nancy C. , Bourke Jared L. , Cooney Melissa J. , Gooi Chi K. , Brown Christopher H. , Arnold John B.
Published: March 2019

Background

Foot and ankle pain is common in the Australian adult population. People with musculoskeletal foot and ankle conditions are often referred for surgical opinion, yet how patients are managed prior to referral is largely unknown. The aim of this study was to determine the characteristics and management of patients with musculoskeletal foot and ankle complaints prior to public‐sector orthopaedic referral in South Australia.

Methods

People with non‐urgent foot or ankle complaints were recruited over a 12‐month period from the waiting‐lists of three tertiary hospitals in Adelaide, Australia. Participants completed a questionnaire on their medical history, duration and location of their foot or ankle complaint, diagnosis of their condition, previous treatment and medical imaging. The Manchester‐Oxford Foot and Ankle Questionnaire, and the EuroQol‐5D‐5 L measured foot/ankle pain severity and health‐related‐quality‐of‐life (HRQoL). Descriptive statistics were generated for sample demographics, medical history and foot/ankle symptoms. Multivariable regressions were used to explore factors associated with foot/ankle pain severity and whether participants considered an operation necessary.

Results

Two hundred and thirty‐three adults returned questionnaires, with a survey response rate of 38.4% (66.1% female, median age 57.7 years IQR 18.5, BMI 29.3 kg/m2 IQR 8.7). Half of the participants had seen a podiatrist (52.8%), and 36.5% did not see any other health professional prior to orthopaedic referral. Sixty‐five (27.9%) had not yet been given a diagnosis. BMI was positively associated with foot/ankle pain severity (β 0.48, 95% CI 0.05, 0.92), while HRQoL had a negative association (β − 0.31, 95% CI ‐0.45, − 0.18). Participants told by their GP that they may need an operation were significantly more likely to consider surgery necessary (OR 31.41, 95% CI 11.30, 87.35), while older people were less likely (OR 0.94, 95% CI 0.90, 0.98).

Conclusions

More than one‐third of the participants had not accessed allied‐health care prior to specialist orthopaedic referral. Participants may consider their GPs opinion on the necessity of surgery compelling, and most expected to undergo surgery, but many couldn't report their diagnosis. The discordance between the expectation of surgery and historically low surgical conversion rates suggests more work is necessary to improve the management of this group.
Elastic reflection waveform inversion with variable density
Authors: Li Yuanyuan , Guo Qiang , Li Zhenchun , Alkhalifah Tariq
Published: March 2019

Elastic full-waveform inversion (FWI) provides a better description of the subsurface information than those given by the acoustic assumption. However, it suffers from a more serious cycle-skipping problem compared with the latter. Reflection waveform inversion (RWI) is able to build a good background model, which can serve as an initial model for elastic FWI. Because, in RWI, we use the model perturbation to explicitly fit reflections, such perturbations should include density, which mainly affects the dynamics. We applied Born modeling to generate synthetic reflection data using optimized perturbations of the P- and S-wave velocities and density. The inversion for the perturbations of the P- and S-wave velocities and density is similar to elastic least-squares reverse time migration. An incorrect background model will lead to misfits mainly at the far offsets, which can be used to update the background P- and S-wave velocities along the reflection wavepath. We optimize the perturbations and background models in an alternate way. We use two synthetic examples and a field-data case to demonstrate our proposed elastic RWI algorithm. The results indicate that our elastic RWI with variable density is able to build reasonably good background models for elastic FWI with the absence of low frequencies, and it can deal with the variable density, which is required in real cases.
3D sharp-boundary inversion of potential-field data with an adjustable exponential stabilizing functional
Authors: Hu Ming , Yu Peng , Rao Chunfeng , Zhao Chongjin , Zhang Luolei
Published: March 2019

Potential-field sharp-boundary inversion will allow us to identify the sharp petrophysical deposit boundaries inside the host rocks. With the purpose to find a more simple and convenient way to achieve a sharp-boundary and well-focused image for 3D focusing inversion, we analyze and discuss the influence of the focusing parameter in several commonly used stabilizing functionals, such as minimum support (MS), minimum gradient support (MGS), modified total variation ([Formula: see text]TV) stabilizing functional, etc. Then, we evaluate an adjustable exponential stabilizing (AES) functional, the focus of which is adjustable by the base and the exponent of the exponential functional, and we apply it to 3D density and magnetic susceptibility inversion for synthetic and field data. Compared with MS, MGS, [Formula: see text]TV, and other stabilizers, the proposed stabilizer can generate well-focused images and provide sharp boundaries. We also determine that sharp-boundary images produced by the proposed AES stabilizer have a weak dependence on the focusing parameter. Furthermore, we can obtain a stable and focused result by controlling the focusing parameter in the exponent of AES adaptively increasing with the iterations. The model tests and inversion of field data verify the flexibility and stability of this adjustable stabilizer.
Direct frequency-domain 3D acoustic solver with intermediate data compression benchmarked against time-domain modeling for full-waveform inversion applications
Authors: Kostin Victor , Solovyev Sergey , Bakulin Andrey , Dmitriev Maxim
Published: March 2019

We have developed a fast direct solver for numerical simulation of acoustic waves in 3D heterogeneous media. The Helmholtz equation is approximated by a 27-point finite-difference stencil of second-order accuracy that is optimized to reduce the numerical dispersion. Due to the optimization, dispersion errors less than 1% are achieved with model discretization of only five points per wavelength. Wave-propagation problem requires solving a large system of linear equations with complex sparse symmetric coefficient matrix with seismic shots representing the right-hand side. The first step is the triangular factorization of the coefficient matrix followed by solving systems of linear equations with triangular coefficient matrices as a second step. Having defined the triangular factors, the second step is very cheap, and its linear scaling with respect to the number of shots is the main advantage of direct methods. To reduce memory consumption and computational time at the factorization step, the lower triangular factors are compressed using a low-rank approximation of their nonzero blocks. The compression enables rapid solving of systems of more than [Formula: see text] equations corresponding to realistic geophysical models. Accuracy and performance comparison of our solver with a highly optimized time-domain solver proves that these approaches complement each other — depending on the problem size and computing configuration, either solver may be preferable.
Remarks on the solid and bulk responses of fluid-filled porous rock
Authors: Tarokh Ali , Makhnenko Roman Y.
Published: March 2019

The volumetric response of fluid-saturated and linearly elastic rock due to a change of either mean stress or pore pressure is characterized by three independent material parameters. The unjacketed bulk modulus is a convenient choice because it can be directly measured in a laboratory test under a loading that preserves the difference between the mean stress and the pore pressure constant. For a monomineralic rock, the measurement of the unjacketed bulk modulus is ignored because it is assumed to be equal to the bulk modulus of the solid phase. To examine this assumption, we tested porous sandstones and limestones mainly composed of quartz and calcite, respectively, under the unjacketed condition. Special attention was dedicated to reaching full saturation ensuring the transmission of the pore pressure to the solid frame. The presence of microscale inhomogeneities, in the form of nonconnected (occluded) pores, was shown to cause a considerable difference between the unjacketed bulk modulus and the bulk modulus of the solid phase. Furthermore, we found the unjacketed bulk modulus to be independent of the unjacketed pressure and Terzaghi effective pressure and therefore a constant.
A grid-search approach for 4D pressure-saturation discrimination
Authors: Dinh Hung Nho , Van der Baan Mirko
Published: March 2019

We develop a grid-search-based inversion method to discriminate between changes of pore pressure and water saturation. In this approach, we build a forward model by combining different rock-physics models and we predict grids of time-lapse attributes within a range of pressure and saturation. The time-lapse measurements from the data are matched with these predicted attributes to find the solution. We suggest using the independent time shifts and time-lapse attenuation to stabilize the inversion result. A synthetic example illustrates the advantages of the inversion workflow. The method helps to visualize how pressure and saturation change the elastic properties. This advantage is also useful in quality control and uncertainty analysis. We apply our method to a real underground blowout example in the North Sea area where gas has leaked into two sand layers at different conditions. We find that gas migrated according to the sand structure with the dipping layer leading to faster migration rates. The inversion results indicate that careful data preparation is crucial, not only to obtain stable inversion performance, but also to capture valuable information when interpreting the blowout development.
Basis-constrained Bayesian Markov-chain Monte Carlo difference inversion for geoelectrical monitoring of hydrogeologic processes
Authors: Oware Erasmus Kofi , Irving James , Hermans Thomas
Published: March 2019

Bayesian Markov-chain Monte Carlo (McMC) techniques are increasingly being used in geophysical estimation of hydrogeologic processes due to their ability to produce multiple estimates that enable comprehensive assessment of uncertainty. Standard McMC sampling methods can, however, become computationally intractable for spatially distributed, high-dimensional problems. We have developed a novel basis-constrained Bayesian McMC difference inversion framework for time-lapse geophysical imaging. The strategy parameterizes the Bayesian inversion model space in terms of sparse, hydrologic-process-tuned bases, leading to dimensionality reduction while accounting for the physics of the target hydrologic process. We evaluate the algorithm on cross-borehole electrical resistivity tomography (ERT) field data acquired during a heat-tracer experiment. We validate the ERT-estimated temperatures with direct temperature measurements at two locations on the ERT plane. We also perform the inversions using the conventional smoothness-constrained inversion (SCI). Our approach estimates the heat plumes without excessive smoothing in contrast with the SCI thermograms. We capture most of the validation temperatures within the 90% confidence interval of the mean. Accounting for the physics of the target process allows the detection of small temperature changes that are undetectable by the SCI. Performing the inversion in the reduced-dimensional model space results in significant gains in computational cost.
Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study
Authors: Wei Andrew H. , Strickland Stephen A. , Hou Jing-Zhou , Fiedler Walter , Lin Tara L. , Walter Roland B. , Enjeti Anoop , Tiong Ing Soo , Savona Michael , Lee Sangmin , Chyla Brenda , Popovic Relja , Salem Ahmed Hamed , Agarwal Suresh , Xu Tu , Fakouhi Kaffa M. , Humerickhouse Rod , Hong Wan-Jen , Hayslip John , Roboz Gail J.
Published: March 2019

PURPOSE

Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML.

PATIENTS AND METHODS

Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS).

RESULTS

Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months).

CONCLUSION

Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.
Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E–Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study
Authors: Van Cutsem Eric , Huijberts Sanne , Grothey Axel , Yaeger Rona , Cuyle Pieter-Jan , Elez Elena , Fakih Marwan , Montagut Clara , Peeters Marc , Yoshino Takayuki , Wasan Harpreet , Desai Jayesh , Ciardiello Fortunato , Gollerkeri Ashwin , Christy-Bittel Janna , Maharry Kati , Sandor Victor , Schellens Jan H.M. , Kopetz Scott , Tabernero Josep
Published: March 2019

PURPOSE

To determine the safety and preliminary efficacy of selective combination targeted therapy for BRAF V600E–mutant metastatic colorectal cancer (mCRC) in the safety lead-in phase of the open-label, randomized, three-arm, phase III BEACON Colorectal Cancer trial ( ClinicalTrials.gov identifier: NCT02928224; European Union Clinical Trials Register identifier: EudraCT2015-005805-35).

PATIENTS AND METHODS

Before initiation of the randomized portion of the BEACON Colorectal Cancer trial, 30 patients with BRAF V600E–mutant mCRC who had experienced treatment failure with one or two prior regimens were to be recruited to a safety lead-in of encorafenib 300 mg daily, binimetinib 45 mg twice daily, plus standard weekly cetuximab. The primary end point was safety, including the incidence of dose-limiting toxicities. Efficacy end points included overall response rate, progression-free survival, and overall survival.

RESULTS

Among the 30 treated patients, dose-limiting toxicities occurred in five patients and included serous retinopathy (n = 2), reversible decreased left ventricular ejection fraction (n = 1), and cetuximab-related infusion reactions (n = 2). The most common grade 3 or 4 adverse events were fatigue (13%), anemia (10%), increased creatine phosphokinase (10%), increased AST (10%), and urinary tract infections (10%). In 29 patients with BRAF V600E–mutant tumors (one patient had a non– BRAF V600E–mutant tumor and was not included in the efficacy analysis), the confirmed overall response rate was 48% (95% CI, 29.4% to 67.5%), median progression-free survival was 8.0 months (95% CI, 5.6 to 9.3 months), and median overall survival was 15.3 months (95% CI, 9.6 months to not reached), with median duration of follow-up of 18.2 months (range, 16.6 to 19.8 months).

CONCLUSION

In the safety lead-in, the safety and tolerability of the encorafenib, binimetinib, and cetuximab regimen is manageable and acceptable for initiation of the randomized portion of the study. The observed efficacy is promising compared with available therapies and, if confirmed in the randomized portion of the trial, could establish this regimen as a new standard of care for previously treated BRAF V600E–mutant mCRC.
Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome
Authors: Simon Stacey L , McWhirter Laura , Diniz Behn Cecilia , Bubar Kate M , Kaar Jill L , Pyle Laura , Rahat Haseeb , Garcia-Reyes Yesenia , Carreau Anne-Marie , Wright Kenneth P , Nadeau Kristen J , Cree-Green Melanie
Published: March 2019

Context

To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS.

Objective

To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI.

Design

Cross-sectional study.

Participants

Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33).

Outcome Measures

Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis.

Results

All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing.

Conclusion

Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.
Serum Uromodulin Is Associated With But Does Not Predict Type 2 Diabetes in Elderly KORA F4/FF4 Study Participants
Authors: Then Cornelia , Then Holger , Meisinger Christa , Heier Margit , Peters Annette , Koenig Wolfgang , Rathmann Wolfgang , Scherberich Jürgen , Seissler Jochen
Published: March 2019

Aims

Serum uromodulin has recently emerged as promising biomarker for kidney function and was suggested to be associated with type 2 diabetes (T2D) in patients with coronary heart disease. Here, we analyzed the association of serum uromodulin with T2D in the population-based KORA F4/FF4 study.

Methods

In 1119 participants of the KORA F4 study aged 62 to 81 years, serum uromodulin was measured, and the association of serum uromodulin with T2D was assessed using logistic and linear regression models stratified for sex. After a mean follow-up time of 6.5 years, 635 participants where re-evaluated. Glucose tolerance status was determined by oral glucose tolerance test at baseline and at the follow-up examination except in cases of known T2D.

Results

Serum uromodulin was inversely associated with T2D in the crude analysis and after adjustment for age and body mass index in men (P < 0.001) and in women (P < 0.05). After further adjustment for estimated glomerular filtration rate, serum uromodulin was significantly inversely associated with T2D in men (P < 0.001) but not in women. Serum uromodulin was not associated with prediabetes after multivariate adjustment and did not predict T2D in men or in women after the follow-up time of 6.5 ± 0.3 years.

Conclusions

In participants of the KORA F4 study, serum uromodulin is independently associated with T2D in men but is not a predictor of future development of T2D.
Recommendations for the packaging and containerizing of bioinformatics software
Authors: Gruening Bjorn , Sallou Olivier , Moreno Pablo , da Veiga Leprevost Felipe , Ménager Hervé , Søndergaard Dan , Röst Hannes , Sachsenberg Timo , O'Connor Brian , Madeira Fábio , Dominguez Del Angel Victoria , Crusoe Michael R. , Varma Susheel , Blankenberg Daniel , Jimenez Rafael C. ,   BioContainers Community, Perez-Riverol Yasset
Published: March 2019

Software Containers are changing the way scientists and researchers develop, deploy and exchange scientific software. They allow labs of all sizes to easily install bioinformatics software, maintain multiple versions of the same software and combine tools into powerful analysis pipelines. However, containers and software packages should be produced under certain rules and standards in order to be reusable, compatible and easy to integrate into pipelines and analysis workflows. Here, we presented a set of recommendations developed by the BioContainers Community to produce standardized bioinformatics packages and containers. These recommendations provide practical guidelines to make bioinformatics software more discoverable, reusable and transparent.  They are aimed to guide developers, organisations, journals and funders to increase the quality and sustainability of research software.
The Application of Omics Technologies to Study Axon Regeneration and CNS Repair
Authors: Tedeschi Andrea , Popovich Phillip G
Published: March 2019

Traumatic brain and spinal cord injuries cause permanent disability. Although progress has been made in understanding the cellular and molecular mechanisms underlying the pathophysiological changes that affect both structure and function after injury to the brain or spinal cord, there are currently no cures for either condition. This may change with the development and application of multi-layer omics, new sophisticated bioinformatics tools, and cutting-edge imaging techniques. Already, these technical advances, when combined, are revealing an unprecedented number of novel cellular and molecular targets that could be manipulated alone or in combination to repair the injured central nervous system with precision. In this review, we highlight recent advances in applying these new technologies to the study of axon regeneration and rebuilding of injured neural circuitry. We then discuss the challenges ahead to translate results produced by these technologies into clinical application to help improve the lives of individuals who have a brain or spinal cord injury.
ОСОБЕННОСТИ ЭФФЕКТИВНОГО ОБУЧЕНИЯ ТЕХНИЧЕСКОМУ ПЕРЕВОДУ СТУДЕНТОВ ПЕРЕВОДЧИКОВ
Authors: Aksenova Daria Alekseevna , Gashkov Sergey Aleksandrovich , Tverdokhlebov Sergey Georgievich , Timofeeva Sofia Pavlovna
Published: March 2019

Цель. Данная статья посвящена вопросам обучения техническому переводу, что является необходимой составляющей переводческой компетенции студентов-специалистов по направлению «Перевод и переводоведение».Метод или методология проведения работы. Основу исследования образуют компаративный и аналитический методы.Результаты. Результаты работы заключаются в том, что при обучении научно-техническому переводу специалист должен получать не только лингвистические, общекультурные знания, но также и технические. Программа обучения в БГТУ «Военмех» включает разделы общеязыковой направленности, специальные научные знания, деловое общение и практику перевода в организациях, которые реализуются в письменной и устной коммуникации.Область применения результатов. Результаты исследования могут быть применены в образовательной сфере.