bluuebunny/crossref_metadata_2025 huggingface dataset:
FFT based approaches in micromechanics: fundamentals, methods and applications
Authors: Lucarini S , Upadhyay M V , Segurado J
Published: October 2021

FFT methods have become a fundamental tool in computational micromechanics since they were first proposed in 1994 by Moulinec and Suquet for the homogenization of composites. Since then many different approaches have been proposed for a more accurate and efficient resolution of the non-linear homogenization problem. Furthermore, the method has been pushed beyond its original purpose and has been adapted to a variety of problems including conventional and strain gradient plasticity, continuum and discrete dislocation dynamics, multi-scale modeling or homogenization of coupled problems such as fracture or multi-physics problems. In this paper, a comprehensive review of FFT approaches for micromechanical simulations will be made, covering the basic mathematical aspects and a complete description of a selection of approaches which includes the original basic scheme, polarization based methods, Krylov approaches, Fourier–Galerkin and displacement-based methods. Then, one or more examples of the applications of the FFT method in homogenization of composites, polycrystals or porous materials including the simulation of damage and fracture will be presented. The applications will also provide an insight into the versatility of the method through the presentation of existing synergies with experiments or its extension toward dislocation dynamics, multi-physics and multi-scale problems. Finally, the paper will analyze the current limitations of the method and try to analyze the future of the application of FFT approaches in micromechanics.
Modeling and experimental validation of thin, tightly rolled dielectric elastomer actuators
Authors: Prechtl J , Kunze J , Moretti G , Bruch D , Seelecke S , Rizzello G
Published: October 2021

Due to their large deformation, high energy density, and high compliance, dielectric elastomer actuators (DEAs) have found a number of applications in several areas of mechatronics and robotics. Among the many types of DEAs proposed in the literature, rolled DEAs (RDEAs) represent one of the most popular configurations. RDEAs can be effectively used as compact muscle-like actuators for soft robots, since they allow eliminating the need for external motors or compressors while providing at the same time a flexible and lightweight structure with self-sensing capabilities. To effectively design and control complex RDEA-driven systems and robots, accurate and numerically efficient mathematical models need to be developed. In this work, we propose a novel lumped-parameter model for silicone-based, thin and tightly rolled RDEAs. The model is grounded on a free-energy approach, and permits to describe the electro-mechanically coupled response of the transducer with a set of nonlinear ordinary differential equations. After deriving the constitutive relationships, the model is validated by means of an extensive experimental campaign, conducted on three RDEA specimens having different geometries. It is shown how the developed model permits to accurately predict the effects of several parameters (external load, applied voltage, actuator geometry) on the RDEA electro-mechanical response, while maintaining an overall simple mathematical structure.
Smart actuation of liquid crystal elastomer elements: cross-link density-controlled response
Authors: Brighenti Roberto , Cosma Mattia Pancrazio
Published: October 2021

Liquid crystal elastomers (LCEs) exhibit some remarkable physical properties, such as the reversible large mechanical deformation induced by proper environmental stimuli of different nature, such as the thermal stimulus, allowing their use as soft actuators. The unique features displayed by LCE are originated from their anisotropic microstructure characterized by the preferential orientation of the mesogen molecules embedded in the polymer network. An open issue in the design of LCEs is how to control their actuation effectiveness: the amount of mesogens molecules, how they are linked to the network, the nematic order degree, the cross-link density are some controllable parameters whose spatial distribution, in general, cannot be tuned except for the last one. In this paper, we develop a theoretical micromechanical-based framework to model and explore the effect of the network cross-link density on the mechanical actuation of LCE elements. In this context, the light-induced polymerization (photopolymerization) for obtaining the elastomers’ cross-linked network is of particular interest, being suitable for precisely tuning the cross-link density distribution within the material. This technology enables to obtain a molecular-scale architected LCEs, allowing the optimal design of the obtainable actuation. The possibility to properly set the cross-link density arrangement within the smart structural element (LCE microstructure design and optimization), represents an intriguing way to create molecular-scale engineered LCE elements having a material microstructure encoding the desired actuation capabilities.
Human arsenic exposure risk via crop consumption and global trade from groundwater-irrigated areas
Authors: Alam Mohammad F , Villholth Karen G , Podgorski Joel
Published: October 2021

While drinking water is known to create significant health risk in arsenic hazard areas, the role of exposure to arsenic through food intake is less well understood, including the impact of food trade. Using the best available datasets on crop production, irrigation, groundwater arsenic hazard, and international crop trade flows, we estimate that globally 17.2% of irrigated harvested area (or 45.2 million hectares) of 42 main crops are grown in arsenic hazard areas, contributing 19.7% of total irrigated crop production, or 418 million metric tons (MMT) per year of these crops by mass. Two-thirds of this area is dedicated to the major staple crops of rice, wheat, and maize (RWM) and produces 158 MMT per year of RWM, which is 8.0% of the total RWM production and 18% of irrigated production. More than 25% of RWM consumed in the South Asian countries of India, Pakistan, and Bangladesh, where both arsenic hazard and degree of groundwater irrigation are high, originate from arsenic hazard areas. Exposure to arsenic risk from crops also comes from international trade, with 10.6% of rice, 2.4% of wheat, and 4.1% of maize trade flows coming from production in hazard areas. Trade plays a critical role in redistributing risk, with the greatest exposure risk borne by countries with a high dependence on food imports, particularly in the Middle East and small island nations for which all arsenic risk in crops is imported. Intensifying climate variability and population growth may increase reliance on groundwater irrigation, including in arsenic hazard areas. Results show that RWM harvested area could increase by 54.1 million hectares (179% increase over current risk area), predominantly in South and Southeast Asia. This calls for the need to better understand the relative risk of arsenic exposure through food intake, considering the influence of growing trade and increased groundwater reliance for crop production.
Towards reducing inter-city economic inequality embedded in China’s environmental protection tax law
Authors: Wang Jingxu , Lin Jintai , Feng Kuishuang , Liu Yu , Jiao Xiaomiao , Ni Ruijing , Du Mingxi , Hubacek Klaus
Published: October 2021

Cities are at the front line of combating environmental pollution and climate change, thus support from cities is crucial for successful enforcement of environmental policy. To mitigate environmental problems, China introduced at provincial level the Environmental Protection Tax Law in 2018. Yet the resulting economic burden on households in different cities with significantly different affluence levels remains unknown. The extent of the economic impacts is likely to affect cities’ support and public acceptability. This study quantifies the economic burden of urban households from taxation of fine particle pollution (PM2.5) for 200 cities nationwide from a ‘consumer’ perspective, accounting for PM2.5 and precursor emissions along the national supply chain. Calculations are based on a multi-regional input–output analysis, the official tax calculation method and urban household consumption data from China’s statistical yearbooks. We find that the current taxation method intensifies economic inequality between cities nationally and within each province, with some of the richest cities having lower tax intensities than some of the poorest. This is due to the fact that taxes are collected based on tax rates of producing regions rather than consuming regions, that cities with very different affluence levels within a province bear the same tax rate, and that emission intensities in several less affluent cities are relatively high. If the tax could be levied based on tax rates of each city where the consumer lives, with tax rates determined based on cities’ affluence levels and with tax revenues used to support emission control, inter-city economic inequality could be reduced. Our work provides quantitative evidence to improve the environmental tax and can serve as the knowledge base for coordinated inter-city policy.
X-type vortex and its effect on beam shaping
Authors: Pang Xiaoyan , Xiao Weiwei , Zhang Han , Feng Chen , Zhao Xinying
Published: October 2021

In this article we propose a new type of optical vortex, the X-type vortex. This vortex inherits and develops the conventional noncanonical vortex, i.e. it no longer has a constant phase gradient around the center, while the intensity keeps invariant azimuthally. The strongly focusing properties of the X-type vortex and its effect on the beam shaping in three-dimensional (3D) fields are analyzed. The interesting phenomena, which cannot be seen in canonical vortices, are observed, for instance the ‘switch effect’ which shows that the intensity pattern can switch from one transverse axis to another in the focal plane by controlling the phase gradient parameter. It is shown that by adjusting the phase gradient of this vortex, the focal field can have marvelous patterns, from the doughnut shape to the shapes with different lobes, and the beam along propagation direction will form a twisting shape in 3D space with controllable rotation direction and location. The physical mechanisms underlying the rule of the beam shaping are also discussed, which generally say that the phase gradient of the X-type vortex, the orbital angular momentum, the polarization and the ‘nongeneric’ characteristic contribute differently in shaping fields. This new type of vortex may supply a new freedom for tailoring 3D optical fields, and our work will pave a way for exploration of new vortices and their applications.
Low pedestal sub-17 fs pulse generation through cascaded self-similar compression in photonic crystal fibers
Authors: Esther Lidiya A , Vasantha Jayakantha Raja R , Varshney Shailendra K
Published: October 2021

We propose a realistic numerical model based on cascaded self-similar pulse compression to generate low pedestal ultrashort pulses at 2.5 µm. Self-similarity in photonic crystal fibers (PCFs) has been attained by modelling exponentially dispersion decreasing and exponentially nonlinearity increasing chalcogenide PCFs. The tapered PCF (TPCF) model is theoretically designed using the fully vectorial effective index method (FVEIM) to obtain accurate effective refractive index, group velocity dispersion (GVD), and Kerr nonlinearity values with low computation time. Initially, fundamental soliton compression in As2S3 tapered PCF is being investigated for the pedestal-free reduction of the pulse width. Subsequently, the compression factor is further enhanced in the As2Se3 PCF-based nonlinear optical loop mirror. The numerical outcomes reveal a compression of 1 ps pulse down to a pulse width of 16.6 fs with a peak power of 116 W in a total fiber length of L = 61 cm.
Mitochondrial genomes do not appear to regulate flowering pattern/reproductive strategy inCannabis sativa
Authors: Attia Ziv , Pogoda Cloe , Vergara Daniela , Kane Nolan C
Published: October 2021

Currently, the amount of genetic data for Cannabis is lacking due to the illegal nature of the plant. Our study used 73 Cannabis sativa whole-genome shotgun libraries to reveal eight different mtDNA haplotypes. The most common haplotype contained 60 of the 73 samples studied and was composed of only dioecious individuals. However, other haplotypes contained a mix of both mating strategies (i.e. monoecious and dioecious). From these haplotype groupings we further examined the fully annotated mitochondrial genomes of four hemp individuals with different mt haplotypes and recorded gene content, copy number variation and synteny. Our results revealed highly syntenic mitochondrial genomes that contained ~60 identifiable sequences for protein-coding genes, tRNAs and rRNAs and no obvious rearrangements or chimeric genes. We found no clear evidence that modern reproductive patterns are due to simple cytoplasmic male sterility mutations. It is likely the interaction between nuclear genetic components and the X/Y sex chromosomes that determines reproductive strategy. Additionally, we added 50 % more mitochondrial genomes to the publicly available repository.
Generalized infinite factorization models
Authors: Schiavon L , Canale A , Dunson D B
Published: October 2021

Factorization models express a statistical object of interest in terms of a collection of simpler objects. For example, a matrix or tensor can be expressed as a sum of rank-one components. In practice, however, it can be challenging to infer the number of components and the relative impact of the different components. A popular idea is to include infinitely many components whose impact decreases with the component index. This article is motivated by two limitations of such existing methods: (i) lack of careful consideration of the within-component sparsity structure; and (ii) not accommodating grouped variables and other nonexchangeable structures. We propose a general class of infinite factorization models that address these limitations. Theoretical support is provided, practical gains are demonstrated in simulation studies, and an ecology application focusing on modelling bird species occurrence is discussed.
Street Skateboarding and the Aesthetic Order of Public Spaces
Authors: Dickinson Sharon , Millie Andrew , Peters Eleanor
Published: October 2021

Street skateboarders are often excluded from public spaces with skating viewed as anti-social or uncivil. In this article, we argue that it can also be regarded as problematic as it interferes with the look and feel of cities as promoted by late-modern capitalism. The article contributes to an aesthetic criminology by arguing that street skateboarding is itself an aesthetic practice, but that this practice challenges the functionality and aesthetic order of the city. The article is supported by evidence from interviews with skateboarders in Manchester, UK. The context is the duel position of skateboarding, being regarded as both deviant and serious leisure (for instance, featuring for the first time in the Olympics in 2021). Rather than criminalizing and excluding skateboarders, it is argued that their aesthetic appreciation of public spaces could add value to city life, that they see and feel the city in ways that ought to add to our emotional and affective appreciation of what it means to live in a city.
Timely childhood vaccination in Israel: a national retrospective study of ethnic and socioeconomic disparities
Authors: Myers Vicki , Saban Mor , Valinsky Liora , Luxenburg Osnat , Wilf-Miron Rachel
Published: October 2021

A large proportion of children do not receive vaccines within the recommended timeframe. This study examined ethnic and socioeconomic differences in age-appropriate immunization of children in Israel, where immunization is freely available. Percent of children receiving MMR/V at 12–13 months, and four doses of DTP/IPV/Hib by 18 months were obtained from the National Programme for Quality Measures between 2015 and 2018. Ethnic group (Jewish vs Arab) (defined by proxy by the neighbourhood in which the clinic was located), neighbourhood socioeconomic status and peripherality were obtained. Rates of MMR vaccination were 61% in the Jewish and 82% in the Arab population; for DPT/IPV/Hib 75% in the Jewish, compared to 92% in the Arab population. These patterns were stable over time. Lowest rates occurred in the most peripheral areas for Arab children, and in urban areas for Jewish children. Differences between ethnic groups were significant at higher SES levels. Greater adherence to the vaccination schedule occurred in the Arab minority in contrast to studies showing lower vaccination in ethnic minorities elsewhere. Lower immunization rates among rural Arab children suggest a need for improved access to clinics. Efforts should be directed towards lower SES groups, while emphasizing the importance of timely vaccination in wealthier groups in order to achieve herd immunity.
Photovoltaic-grid control method based on self-gain system compensation
Authors: Tang Junci , Li Tie , Pi Junbo , Cui Dai
Published: October 2021

The presence of decentralized production in modern electrical systems precludes traditional automatic generation control (AGC) strategies. Renewable energy production is highly dependent on the environment; for example, photovoltaic (PV) system, but its power generation is very unstable, which makes power grids containing PV systems face greater challenges. In this paper, we propose a PV-grid control method based on self-gain system compensation to reduce the negative effects of large fluctuations and uncertainties in solar energy production. First, the performance characteristics of solar modules are discussed and a multi-region model with a system with high penetration of solar systems is built. The AGC power is then displayed with different power variations according to different maximum power point tracking methods to analyze the uncertainty and variation of the PV output power and its effects on the AGC. We have also developed and implemented a compensation unit to eliminate the negative effects of PV power on AGC. Finally, the proposed method was demonstrated using the load from the example step as a disturbance variable to obtain a dynamic model of a dual-zone switched grid AGC with two PV systems based on a DMPC-distributed model. As a result of the simulation, the proposed method in this paper can guarantee the excellent properties of the dynamic behavior of the AGC system with large variations and high uncertainty of the PV system, and the validity of the proposed method have also been confirmed.
Portfolio optimization and intergenerational risk sharing for a collective defined contribution pension plan
Authors: Wang Suxin , Wang Peiqi , Zhang Shuhua
Published: October 2021

In this paper, we use a continuous time stochastic model to study a collective defined contribution pension plan when the interest rate is stochastic, and where the benefit levels are adjusted depending on the performance of the plan, and with risk sharing between different generations. The nominal interest rate is characterized by the Vasicek model, and the pension fund is invested in a financial market consisting of three assets: one risk-free asset, one bond and one risky asset. The participants of the pension plan are the risk bearers, and the plan seeks optimal investment and risk-sharing arrangements for plan sponsors and participants that maximize the expected accumulated discount utility of intermediate benefit adjustments and terminal wealth. Closed-form solutions are derived via the stochastic optimal control approach under constant relative risk aversion utility function. Numerical results show the effects of financial market parameters on the optimal investment strategy and how the optimal benefit changes with respect to different risk aversions and wage increase rates.
Comparison of radio-isotope method with 99m technetium and near-infrared fluorescent imaging with indocyanine green for sentinel lymph node detection in endometrial cancer
Authors: Togami Shinichi , Ushiwaka Takashi , Fukuda Mika , Mizuno Mika , Yanazume Shintaro , Kamio Masaki , Kobayashi Hiroaki
Published: October 2021

Background

We aimed to compare the detection rate of pelvic sentinel lymph node between the radio-isotope with 99m technetium (99mTc)-labeled phytate and near-infrared fluorescent imaging with indocyanine green in patients with endometrial cancer.

Methods

This study included 122 patients who had undergone sentinel lymph node mapping using 99mTc and indocyanine green. In the radio-isotope method, sentinel lymph nodes were detected using uterine cervix 99mTc injections the day before surgery. Following injection, the number and locations of the sentinel lymph nodes were evaluated by lymphoscintigraphy. In addition, indocyanine green was injected into the cervix immediately before surgery.

Results

The overall pelvic sentinel lymph node detection rate (at least one pelvic sentinel lymph node detected) was not significantly different between 99mTc (95.9% [117/122]) and indocyanine green (94.3% [115/122]). Similarly, the bilateral sentinel lymph node detection rate was not significantly different between 99mTc (87.7% [107/122]) and indocyanine green (79.5% [97/122]). More than two sentinel lymph nodes per unilateral pelvic lymph node were found in 12.3% (15/122) and 27% (33/122) of cases with 99mTc and indocyanine green, respectively, in the right pelvic side, and 11.5% (14/122) and 32.8% (40/122) of cases with 99mTc and indocyanine green, respectively, in the left pelvic side. indocyanine green showed that there were significantly more than two sentinel lymph nodes in either the left or right pelvic sentinel lymph nodes (P < 0.0001). There was a significant difference in the mean number of total pelvic sentinel lymph nodes between 99mTc (2.2) and indocyanine green (2.5) (P = 0.028) methods.

Conclusion

Although indocyanine green is useful for sentinel lymph node identification, we believe it is better to use it in combination with 99mTc until the surgeon is accustomed to it.
Cordycepin induces M1/M2 macrophage polarization to attenuate the liver and lung damage and immunodeficiency in immature mice with sepsis via NF-κB/p65 inhibition
Authors: Zhang Yudan , Cheng Jing , Su Yufei , Li Mingyue , Wen Jun , Li Sixiu
Published: October 2021

Objectives

To explore the impacts of cordycepin and underlying mechanism on the sepsis.

Methods

The sepsis mice model was built and treated with different concentrations of cordycepin. Then the liver and lung injury caused by cecal ligation and puncture (CLP) was assessed using H&E staining and TUNEL assay. The expression of relevant genes was detected using qRT-PCR analysis and ELISA assays. Besides, the macrophage polarization was checked by flow cytometry.

Key findings

Cordycepin could significantly improve the liver and lung injury. Moreover, cordycepin increased the distribution of F4/80+ CD206+ M2-like macrophages and F4/80+ iNOS+ M1-like macrophages through down-regulating the expression of relevant genes. More importantly, cordycepin could monitor the protein expression of iNOS, Arg-1, TNF-α, MCP-1, IL-4 and IL-10 in CLP mice. Meanwhile, the elevated level of p65 induced by CLP was also repressed by the increase of the cordycepin. Moreover, cordycepin played a crucial part in CLP mice through modulating the NF-κB/p65 signalling pathway.

Conclusions

Cordycepin played an important role in mice with sepsis via reducing the M1/M2 macrophage polarization and modulating the NF-κB/p65 signalling pathway.
Saturation of large-scale dynamo in anisotropically forced turbulence
Authors: Bhat Pallavi
Published: October 2021

Turbulent dynamo theories have faced difficulties in obtaining evolution of large-scale magnetic fields on short dynamical time-scales due to the constraint imposed by magnetic helicity balance. This has critical implications for understanding the large-scale magnetic field evolution in astrophysical systems like the Sun, stars and galaxies. Direct numerical simulations (DNS) in the past with isotropically forced helical turbulence have shown that large-scale dynamo saturation time-scales are dependent on the magnetic Reynolds number (Rm). In this work, we have carried out periodic box DNS of helically forced turbulence leading to a large-scale dynamo with two kinds of forcing function, an isotropic one based on that used in Pencil-Code and an anisotropic one based on Galloway-Proctor flows. We show that when the turbulence is forced anisotropically, the nonlinear (saturation) behaviour of the large-scale dynamo is only weakly dependent on Rm. In fact the magnetic helicity evolution on small and large scales in the anisotropic case is distinctly different from that in the isotropic case. This result possibly holds promise for the alleviation of important issues like catastrophic quenching.
The promise of the Maker Movement: policy expectations versus community criticisms
Authors: Ferretti Federico , van Lente Harro
Published: October 2021

The rise of the Maker Movement brings along promises of extended citizen participation to science and innovation. In this paper, we investigate policy expectations about the Maker Movement and contrast them with views about science and society prevailing within communities of the movement itself. The analysis is based on a study of European Union policy documents and interviews with experts and practitioners of the Maker Movement. We obtain a self-portrait of the Maker Movement characterized by a set of aspirations, values, and motivations about the science–society relationship that deviate from of policy expectations. We conclude that, the Maker Movement, apart from being a target of policy hopes of increased citizen participation in science and innovation, can also be characterized as a source bed of criticism of mainstream science and innovation. The tension between policy expectations and community criticisms provides lessons for both sides.
On Information Rank Deficiency in Phenotypic Covariance Matrices
Authors: O’Keefe F Robin , Meachen Julie A , Polly P David
Published: October 2021

This article investigates a form of rank deficiency in phenotypic covariance matrices derived from geometric morphometric data, and its impact on measures of phenotypic integration. We first define a type of rank deficiency based on information theory then demonstrate that this deficiency impairs the performance of phenotypic integration metrics in a model system. Lastly, we propose methods to treat for this information rank deficiency. Our first goal is to establish how the rank of a typical geometric morphometric covariance matrix relates to the information entropy of its eigenvalue spectrum. This requires clear definitions of matrix rank, of which we define three: the full matrix rank (equal to the number of input variables), the mathematical rank (the number of nonzero eigenvalues), and the information rank or “effective rank” (equal to the number of nonredundant eigenvalues). We demonstrate that effective rank deficiency arises from a combination of methodological factors—Generalized Procrustes analysis, use of the correlation matrix, and insufficient sample size—as well as phenotypic covariance. Secondly, we use dire wolf jaws to document how differences in effective rank deficiency bias two metrics used to measure phenotypic integration. The eigenvalue variance characterizes the integration change incorrectly, and the standardized generalized variance lacks the sensitivity needed to detect subtle changes in integration. Both metrics are impacted by the inclusion of many small, but nonzero, eigenvalues arising from a lack of information in the covariance matrix, a problem that usually becomes more pronounced as the number of landmarks increases. We propose a new metric for phenotypic integration that combines the standardized generalized variance with information entropy. This metric is equivalent to the standardized generalized variance but calculated only from those eigenvalues that carry nonredundant information. It is the standardized generalized variance scaled to the effective rank of the eigenvalue spectrum. We demonstrate that this metric successfully detects the shift of integration in our dire wolf sample. Our third goal is to generalize the new metric to compare data sets with different sample sizes and numbers of variables. We develop a standardization for matrix information based on data permutation then demonstrate that Smilodon jaws are more integrated than dire wolf jaws. Finally, we describe how our information entropy-based measure allows phenotypic integration to be compared in dense semilandmark data sets without bias, allowing characterization of the information content of any given shape, a quantity we term “latent dispersion”. [Canis dirus; Dire wolf; effective dispersion; effective rank; geometric morphometrics; information entropy; latent dispersion; modularity and integration; phenotypic integration; relative dispersion.]
Revisiting the X:BOT Naltrexone Clinical Trial Using a Comprehensive Survival Analysis
Authors: Ajazi Elizabeth M. , Dasgupta Nabarun , Marshall Stephen W. , Monaco Jane , Howard Annie Green , Preisser John S. , Schwartz Todd A.
Published: October 2021

Objectives

This paper illustrates survival models for analysis of trials of substance use treatment programs. It uses public release data from a study of extended-release naltrexone (XR-NTX), relative to buprenorphine-naloxone (BUP-NX).

Methods

We used publicly available data from the X:BOT trial (n = 570), which compared XR-NTX to BUP-NX on 2 efficacy outcomes (opioid relapse, use of nonprescribed opioids; positive opioid urine test) and 1 safety outcome (overdose). Intention-to-treat (ITT) and per-protocol approaches were implemented using survival models that included treatment-by-time interactions.

Results

Consistent with the original trial findings, 72% of XR-NTX and 94% of BUP-NX subjects initiated treatment; the ITT hazard ratio for XR-NTX relative to BUP-NX was 1.40 (95% confidence interval: 1.13, 1.73; P < 0.01) for opioid relapse and 1.31 (1.07, 1.60; P = 0.01) for positive urine test. Using treatment-by-time interactions, we examined the time-dependent effect of XR-NTX and found an elevated ITT overdose hazard ratio of 2.4 (1.1, 5.3; P = 0.03) overall and 3.8 (1.2, 11.6; P = 0.02) during the study treatment phase. This result (28 overdoses overall; 17 overdoses during the study treatment phase) contrasts with the previous analysis, which reported minimal differences in overdose between XR-NTX and BUP-NX.

Conclusions

An advantage of using time-dependent Cox models is its ability to isolate effects during specific periods. In general, our survival analyses concur with the conclusions of Lee et al (2018) for the efficacy outcomes, which demonstrated superiority of BUP-NX. In contrast to the original report, our analysis indicates a greater risk of overdose for XR-NTX, predominantly during the study treatment phase. Further investigation of this finding is a pressing research priority.
Open Ankle Fractures: What Predicts Infection? A Multicenter Study
Authors: Cooke Margaret E. , Tornetta Paul , Firoozabadi Reza , Vallier Heather , Weinberg Douglas S. , Alton Timothy B. , Dillman Megan R. , Westberg Jerald R. , Schmidt Andrew , Bosse Michael , Leas Daniel P. , Archdeacon Michael , Kakazu Rafael , Nzegwu Ifeanyi , OToole Robert V. , Costales Timothy G. , Coale Max , Mullis Brian , Usmani Rashad H. , Egol Kenneth , Kottmeier Stephen , Sanders David , Jones Cliff , Miller Anna N. , Horwitz Daniel S. , Kempegowda Harish , Morshed Saam , Belaye Tigist , Teague David
Published: October 2021

Objective:

To identify the patient, injury, and treatment factors associated with an acute infection during the treatment of open ankle fractures in a large multicenter retrospective review. To evaluate the effect of infectious complications on the rates of nonunion, malunion, and loss of reduction.

Design:

Multicenter retrospective review.

Setting:

Sixteen trauma centers.

Patients:

One thousand and 3 consecutive skeletally mature patients (514 men and 489 women) with open ankle fractures.

Main Outcome Measures:

Fracture-related infection (FRI) in open ankle fractures.

Results:

The charts of 1003 consecutive patients were reviewed, and 712 patients (357 women and 355 men) had at least 12 weeks of clinical follow-up. Their average age was 50 years (range 16–96), and average BMI was 31; they sustained OTA/AO types 44A (12%), 44B (58%), and 44C (30%) open ankle fractures. The rate FRI rate was 15%. A multivariable regression analysis identified male sex, diabetes, smoking, immunosuppressant use, time to wound closure, and wound location as independent risk factors for infection. There were 77 cases of malunion, nonunion, loss of reduction, and/or implant failure; FRI was associated with higher rates of these complications (P = 0.01).

Conclusions:

Several patient, injury, and surgical factors were associated with FRI in the treatment of open ankle fractures.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
A Novel CD3/BCMA Bispecific T-cell Redirecting Antibody for the Treatment of Multiple Myeloma
Authors: Xiong Mengshang , Liu Ruoqi , Lei Xiaomin , Fan Dongmei , Lin Fangzhen , Hao Wei , Yuan Xiangfei , Yang Yuanyuan , Zhang Xiaolong , Ye Zhou , Lu Yang , Zhang Yanjun , Wang Jianxiang , Xiong Dongsheng
Published: October 2021

Multiple myeloma (MM) is a B-cell malignancy for which new treatments are urgently needed. Redirecting the activity of T cells by bispecific antibodies against tumor cells is a potent approach. The B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein and therefore is an ideal therapeutic target for T-cell redirecting therapies. The main objective of this work is to target the BCMA by generating BCMA-specific murine monoclonal antibody and construct a cluster of differentiation 3 (CD3)/BCMA-directed tandem diabodies (Tandab). In brief, using standard hybridoma technology, we developed a novel BCMA-specific monoclonal antibody (clone 69G8), that specifically bind with BCMA+ cell lines and MM patient sample; whereas BCMA− cells were not recognized. For T cells by bispecific antibodies application, we constructed a Tandab (CD3/BCMA) simultaneously targeting both CD3 and BCMA and our studies demonstrated that Tandab (CD3/BCMA) was functional with specific binding capability both for CD3+ cells and BCMA+ cells. It induced selective, dose-dependent lysis of BCMA+ cell lines, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA− cells were not affected. Furthermore, we demonstrated that Tandab activity correlates with BCMA expression, with higher potency observed in highly BCMA expressing tumor cells. In vivo, the purified Tandab (CD3/BCMA) significantly inhibited the tumor growth in a subcutaneous NCI-H929 xenograft model. Taken together, these results show that the Tandab (CD3/BCMA) displays potent and selective anti-MM activities and represents a promising immunotherapeutic for the treatment of MM.
Revisiting the g-null Paradox
Authors: McGrath Sean , Young Jessica G. , Hernán Miguel A.
Published: October 2021

The (noniterative conditional expectation) parametric g-formula is an approach to estimating causal effects of sustained treatment strategies from observational data. An often-cited limitation of the parametric g-formula is the g-null paradox: a phenomenon in which model misspecification in the parametric g-formula is guaranteed in some settings consistent with the conditions that motivate its use (i.e., when identifiability conditions hold and measured time-varying confounders are affected by past treatment). Many users of the parametric g-formula acknowledge the g-null paradox as a limitation when reporting results but still require clarity on its meaning and implications. Here, we revisit the g-null paradox to clarify its role in causal inference studies. In doing so, we present analytic examples and a simulation-based illustration of the bias of parametric g-formula estimates under the conditions associated with this paradox. Our results highlight the importance of avoiding overly parsimonious models for the components of the g-formula when using this method.
Accrediting Graduate Programs in Healthcare Quality and Safety
Authors: Oglesby Willie H. , Hall Allyson G. , Valenta Annette L. , Harwood Kenneth J. , McCaughey Deidre , Feldman Sue , Stanowski Anthony C. , Chrapah Sandra , Chenot Teri , Brichto Eric , Nash David B.
Published: October 2021

The number of master’s degree programs in healthcare quality and safety (HQS) has increased significantly over the past decade. Academic accreditation provides assurance that educational programs are of a high quality and meet the needs of students, employers, and the general public. Under the guidance of the Commission on Accreditation of Healthcare Management Education, faculty from 9 universities collaborated in the development of criteria and related content domains to be used in the accreditation of graduate programs in HQS. Thirteen content domains were identified. Four of the content domains, safety and error science, improvement science and quality principles, evidence-based practice, and measurement and process improvement are thought to be foundational domains for graduate education in HQS. This article describes the development of the content domains and accompanying standards for accreditation of graduate programs in HQS.
The Impacts of COVID-19 on Mental Health and Training in US Professional Endurance Athletes
Authors: Roche Megan , Sainani Kristin , Noordsy Douglas , Fredericson Michael
Published: October 2021

Objective:

We examined how professional athletes are affected by COVID-19. Our primary aim was to assess changes in mental health that occurred after COVID-19 restrictions, and our secondary aim was to assess changes in exercise volume and intensity.

Design:

Cross-sectional study.

Setting:

United States.

Participants:

Strava professional endurance athletes.

Assessment of Risk Factors:

Participants completed a survey, and a subset of participants consented to have their activity data analyzed. The survey included questions on COVID-19 symptoms, exercise, and mental health, as measured by a modified Patient Health Questionnaire.

Main Outcome Measures:

Participants were asked about 2 periods in 2020: before COVID-19 (January 1-March 14) and during COVID-19 (March 15-August 25), and activity data from both periods were downloaded. Activity data consisted of Global Positioning System and self-reported uploads.

Results:

One hundred thirty-one male and female Strava athletes were enrolled, and a subset of athletes (n = 114) consented to have their activity data analyzed. During COVID-19 restrictions, 22.2% of participants reported feeling down or depressed and 27.4% of participants reported feeling nervous or anxious at least half the days in a week compared with 3.8% and 4.6% before COVID-19 restrictions, respectively (P < 0.0001). Activity data revealed a significant increase (P < 0.0001) in exercise minutes per day during COVID-19 (mean = 103.00, SD = 42.1) compared with before COVID-19 restrictions (mean = 92.4, SD = 41.3), with no significant changes in intensity.

Conclusions:

Athletes reported significant increases in feeling down or depressed and nervous or anxious despite an increase in exercise duration during COVID-19. Future research should assess how to support athletes with mental health resources.
Resection or ablation versus transarterial therapy for Child-Pugh A patients with a single small hepatocellular carcinoma
Authors: Suh Young Ju , Jin Young-Joo , Jeong Yujin , Shin Woo Young , Lee Jeong-min , Cho Soongu , Yu Jung Hwan , Lee Jin-Woo
Published: October 2021

Data from a direct comparison of the long-term survival outcomes of surgical resection (SR) or radiofrequency ablation (RFA) versus transarterial therapy in Child-Turcotte-Pugh (CTP)-class A patients with a single small T1/T2 stage hepatocellular carcinoma (HCC) (≤3 cm) are still lacking. This study retrospectively compared the therapeutic outcomes of these treatment types for CTP-A patients with a single small HCC.

Using a nationwide Korean registry, we identified 2314 CTP-A patients with SR (n = 722), RFA (n = 731), or transarterial therapy (n = 861) for a single (≤3 cm) T1/T2 stage HCC from 2008 to 2014. The posttreatment overall survival (OS) of transarterial therapy with either SR or RFA were compared using the Inverse Probability of treatment Weighting (IPW). The median follow-up period was 50 months (range 1–107 months).

After IPW, the cumulative OS rates after SR or RFA were significantly higher than those after transarterial therapy in all subjects (all P values < .05). The OS rates after SR or RFA were better than those after transarterial therapy in patients with the hepatitis B or C virus (all P values < .05), and in patients aged <65 years (all P values < .05). The cumulative OSs between RFA and transarterial therapy were statistically comparable in patients with a 2 to 3 cm HCC and aged ≥65 years, respectively. For all subjects, the weighted Cox proportional hazards model using IPW provided the adjusted hazard ratios (95% confidence interval) for the OS after SR versus transarterial therapy and after RFA versus transarterial therapy of 0.42 (0.30–0.60) (P < .001) and 0.78 (0.61–0.99) (P = .044), respectively.

In CTP-A patients with a single (≤3 cm) T1/T2 HCC, SR or RFA provides a better OS than transarterial therapy, regardless of the HCC etiology (hepatitis B virus or hepatitis C virus), especially in patients with HCC of <2 cm and aged <65 years.
Pembrolizumab-induced focal segmental glomerulosclerosis
Authors: Kim Da Woon , Jeon Hakeong , Kim Sungmi , Lee Wanhee , Kim Hyo Jin , Rhee Harin , Song Sang Heon , Seong Eun Young
Published: October 2021

Rationale:

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder that leads to end-stage kidney disease. Pembrolizumab, an immune checkpoint inhibitor, is an anti-programmed death 1 (PD-1) immunoglobulin G4 antibody approved for the treatment of advanced melanoma and can cause various renal immune-related adverse events (AEs), including acute kidney injury. Several cases of anti PD-1 therapy-induced glomerulonephritis have been reported so far, but FSGS has seldom been reported.

Patient concerns:

46-year old woman presented to our hospital with generalized edema.

Diagnoses:

Laboratory examination revealed features of nephrotic syndrome, and kidney biopsy confirmed FSGS. After other etiological factors of secondary FSGS were ruled out, she was diagnosed with FSGS caused by pembrolizumab.

Interventions:

She did not resume treatment with pembrolizumab and was treated with irbesartan and furosemide according to the American Society of Clinical Oncology Practice guidelines.

Outcomes:

After 2 months, the features of nephrotic syndrome resolved.

Lessons:

This case provides valuable insight into the etiology of FSGS that can occur as a renal immune-related AE of PD-1 inhibitor therapy. Therefore, patients should undergo evaluation for renal function and urinalysis at baseline and after treatment. If patients treated with PD-1 inhibitors present with renal injury and/or unexplained proteinuria >1 g/day, we would recommend a kidney biopsy to determine the underlying cause and establish an appropriate therapeutic plan.
Simple prognostic markers for optimal treatment of patients with unresectable pancreatic cancer
Authors: Terao Takashi , Kumagi Teru , Hyodo Ichinosuke , Yokota Tomoyuki , Azemoto Nobuaki , Miyata Hideki , Kuroda Taira , Ohno Yoshinori , Tanaka Yoshinori , Shibata Naozumi , Imamura Yoshiki , Kanemitsu Kozue , Miyake Teruki , Koizumi Mitsuhito , Hiasa Yoichi
Published: October 2021

Most patients with pancreatic cancer are ineligible for curative resection at diagnosis, resulting in poor prognosis. This study aimed to evaluate the prognostic factors in patients with unresectable pancreatic cancer.

We retrospectively collected clinical data from 196 patients with unresectable pancreatic cancer who received palliative chemotherapy (N = 153) or palliative care alone (N = 43) from January 2011 to December 2013. Patients’ background data and overall survival were analyzed using the Cox proportional hazard regression model.

In patients receiving palliative chemotherapy (gemcitabine-based regimen, 88.2%) and palliative care alone, the median (range) ages were 68 (43–91) and 78 (53–90) years, and metastatic diseases were present in 80% (N = 123) and 86% (N = 37), respectively. Multivariate analysis in the palliative chemotherapy patients showed that liver metastasis (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.58–3.20, P < .001), neutrophil-to-lymphocyte ratio (>4.5 vs ≤4.5; HR 3.45, 95% CI 2.22–5.36, P < .001), and cancer antigen 19-9 (CA19-9) (≥900 vs <900 U/mL; HR 1.45, 95% CI 1.02–2.05, P = .036) were independent prognostic factors. In those receiving palliative care alone, lung (HR 3.27, 95% Cl 1.46-7.35, p = 0.004) and peritoneum (HR 2.50, 95% CI 1.20–5.18, P = .014) metastases and the C-reactive protein-to-albumin ratio (≥1.3 vs <1.3; HR 3.33, 95% Cl 1.51–7.35, P = .003) were independent prognostic factors. Furthermore, patients with multiple factors had worse prognosis in both groups. Median survival time of palliative chemotherapy patients with risk factors 0, 1, 2, and 3 were 13.1 (95% CI 8.0–16.9), 9.4 (95% CI 7.9–10.1), 6.6 (95% CI 4.9–7.8), and 2.5 (95% CI 1.7–4.0) months, respectively. Similarly, median survival time was 5.7 (95% CI 1.3 -8.0), 2.1 (95% CI 1.5–3.9), and 1.3 (95% CI 0.6–1.7) months, respectively, for palliative care alone patients with risk factor 0, 1, and 2 to 3.

Prognostic markers for pancreatic cancer were neutrophil-to-lymphocyte ratio, liver metastasis, and CA19-9 in patients undergoing palliative chemotherapy and C-reactive protein-to-albumin ratio and lung/peritoneum metastases in patients undergoing palliative care alone. These simple markers should be considered when explaining the prognosis and therapeutic options to patients.
Association between SOCS3 hypermethylation and HBV-related hepatocellular carcinoma and effect of sex and age
Authors: Zheng Hairu , Yan Yanggang , Cheng Jiajia , Yu Shuyong , Wang Yong
Published: October 2021

Background:

Suppressor 3 of cytokine signaling (SOCS3) hypermethylation has been reported to participate in hepatocellular carcinoma (HCC) development and progression, but conflicting results were published. This study aimed to analyze the clinical effects of SOCS3 hypermethylation in HCC and the effects of sex and age on SOCS3 hypermethylation in HCC.

Methods:

Databases were searched for relevant case-control and cohort studies on SOCS3 hypermethylation in HBV-related HCC. In vitro and in vivo studies and studies of patients with serious comorbidities were excluded. Review Manager 5.2 was used to estimate the effects of the results among the selected studies. Forest plots, sensitivity analysis, and bias analysis for the included studies were also conducted.

Results:

Finally, 8 relevant studies met the inclusion criteria. A significant difference in SOCS3 hypermethylation in HCC was found between tumor and nontumor groups (the odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.48–2.73, P < .00001; P for heterogeneity = .39, I
2 = 5%). The meta-analysis suggested no significant difference in the effect of sex (OR = 1.00, 95% CI: 0.76–1.31, P = .76; P for heterogeneity = .44, I
2 = 0%) and age on SOCS3 hypermethylation in HCC (OR = 1.11, 100% CI: 0.78–1.29, P = .03; P for heterogeneity = .14, I
2 = 36%). Limited publication bias was observed in this study.

Conclusion:

SOCS3 hypermethylation is associated with HBV-related HCC. Sex and age do not affect the association between SOCS3 hypermethylation and HCC. SOCS3 might be a treatment target for HCC.