bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratumoral Plasmid IL12 Expands CD8+ T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti–PD-1 Therapy
Authors: Telli Melinda L. , Nagata Hiroshi , Wapnir Irene , Acharya Chaitanya R. , Zablotsky Kaitlin , Fox Bernard A. , Bifulco Carlo B. , Jensen Shawn M. , Ballesteros-Merino Carmen , Le Mai Hope , Pierce Robert H. , Browning Erica , Hermiz Reneta , Svenson Lauren , Bannavong Donna , Jaffe Kim , Sell Jendy , Foerter Kellie Malloy , Canton David A. , Twitty Christopher G. , Osada Takuya , Lyerly H. Kim , Crosby Erika J.
Published: February 2021

Purpose:

Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.

Patients and Methods:

Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets.

Results:

Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti–PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti–PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response.

Conclusions:

These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma
Authors: Armstrong Andrew J. , Nixon Andrew B. , Carmack Andrea , Yang Qian , Eisen Tim , Stadler Walter M. , Jones Robert J. , Garcia Jorge A. , Vaishampayan Ulka N. , Picus Joel , Hawkins Robert E. , Hainsworth John D. , Kollmannsberger Christian K. , Logan Theodore F. , Puzanov Igor , Pickering Lisa M. , Ryan Christopher W. , Protheroe Andrew , George Daniel J. , Halabi Susan
Published: February 2021

Purpose:

Biomarkers are needed in patients with non–clear cell renal cell carcinomas (NC-RCC) to inform treatment selection but also to identify novel therapeutic targets. We thus sought to profile circulating angiokines in the context of a randomized treatment trial of everolimus versus sunitinib.

Patients and Methods:

ASPEN (NCT01108445) was an international, randomized, open-label phase II trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC with no prior systemic therapy. Patients were randomized to everolimus or sunitinib and treated until disease progression or unacceptable toxicity. The primary endpoint was radiographic progression-free survival (PFS) defined by RECIST 1.1. Plasma angiokines were collected at baseline, cycle 3, and progression and associated with PFS and overall survival (OS).

Results:

We enrolled 108 patients, 51 received sunitinib and 57 everolimus; of these, 99 patients had evaluable plasma for 23 angiokines. At the final data cutoff, 94 PFS and 64 mortality events had occurred. Angiokines that were independently adversely prognostic for OS were osteopontin (OPN), TIMP-1, thrombospondin-2 (TSP-2), hepatocyte growth factor (HGF), and VCAM-1, and these were also associated with poor-risk disease. Stromal derived factor 1 (SDF-1) was associated with improved survival. OPN was also significantly associated with worse PFS. No statistically significant angiokine-treatment outcome interactions were observed for sunitinib or everolimus. Angiopoeitin-2 (Ang-2), CD-73, HER-3, HGF, IL6, OPN, PIGF, PDGF-AA, PDGF-BB, SDF-1, TGF-b1-b2, TGFb-R3, TIMP-1, TSP-2, VCAM-1, VEGF, and VEGF-R1 levels increased with progression on everolimus, while CD-73, ICAM-1, IL6, OPN, PlGF, SDF-1, TGF-b2, TGFb-R3, TIMP-1, TSP-2, VEGF, VEGF-D, and VCAM-1 increased with progression on sunitinib.

Conclusions:

In patients with metastatic NC-RCC, we identified several poor prognosis angiokines and immunomodulatory chemokines during treatment with sunitinib or everolimus, particularly OPN.
Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Authors: Pullarkat Vinod A. , Lacayo Norman J. , Jabbour Elias , Rubnitz Jeffrey E. , Bajel Ashish , Laetsch Theodore W. , Leonard Jessica , Colace Susan I. , Khaw Seong Lin , Fleming Shaun A. , Mattison Ryan J. , Norris Robin , Opferman Joseph T. , Roberts Kathryn G. , Zhao Yaqi , Qu Chunxu , Badawi Mohamed , Schmidt Michelle , Tong Bo , Pesko John C. , Sun Yan , Ross Jeremy A. , Vishwamitra Deeksha , Rosenwinkel Lindsey , Kim Su Young , Jacobson Amanda , Mullighan Charles G. , Alexander Thomas B. , Stock Wendy
Published: February 2021

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-XL/BCL2 inhibitor, may allow targeting of both BCL2 and BCL-XL without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population.

Significance:

In this phase I study, venetoclax with low-dose navitoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes and in those who failed available therapies including stem cell transplant.

See related commentary by Larkin and Byrd, p. 1324.

This article is highlighted in the In This Issue feature, p. 1307
Arrhythmias in Cardiac Sarcoidosis Bench to Bedside
Authors: Rosenfeld Lynda E. , Chung Mina K. , Harding Clifford V. , Spagnolo Paolo , Grunewald Johan , Appelbaum Jason , Sauer William H. , Culver Daniel A. , Joglar Jose A. , Lin Ben A. , Jellis Christine L. , Dickfeld Timm-Michael , Kwon Deborah H. , Miller Edward J. , Cremer Paul C. , Bogun Frank , Kron Jordana , Bock Ashley , Mehta Davendra , Leis Paul , Siontis Konstantinos C. , Kaufman Elizabeth S. , Crawford Thomas , Zimetbaum Peter , Zishiri Edwin T. , Singh Jagmeet P. , Ellenbogen Kenneth A. , Chrispin Jonathan , Quadri Syed , Vincent Logan L. , Patton Kristen K. , Kalbfleish Steven , Callahan Thomas D. , Murgatroyd Francis , Judson Marc A. , Birnie David , Okada David R. , Maulion Christopher , Bhat Pavan , Bellumkonda Lavanya , Blankstein Ron , Cheng Richard K. , Farr Maryjane A. , Estep Jerry D.
Published: February 2021

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and
18
F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.
Deep Neural Networks Can Predict New-Onset Atrial Fibrillation From the 12-Lead ECG and Help Identify Those at Risk of Atrial Fibrillation–Related Stroke
Authors: Raghunath Sushravya , Pfeifer John M. , Ulloa-Cerna Alvaro E. , Nemani Arun , Carbonati Tanner , Jing Linyuan , vanMaanen David P. , Hartzel Dustin N. , Ruhl Jeffery A. , Lagerman Braxton F. , Rocha Daniel B. , Stoudt Nathan J. , Schneider Gargi , Johnson Kipp W. , Zimmerman Noah , Leader Joseph B. , Kirchner H. Lester , Griessenauer Christoph J. , Hafez Ashraf , Good Christopher W. , Fornwalt Brandon K. , Haggerty Christopher M.
Published: February 2021

Background:

Atrial fibrillation (AF) is associated with substantial morbidity, especially when it goes undetected. If new-onset AF could be predicted, targeted screening could be used to find it early. We hypothesized that a deep neural network could predict new-onset AF from the resting 12-lead ECG and that this prediction may help identify those at risk of AF-related stroke.

Methods:

We used 1.6 M resting 12-lead digital ECG traces from 430 000 patients collected from 1984 to 2019. Deep neural networks were trained to predict new-onset AF (within 1 year) in patients without a history of AF. Performance was evaluated using areas under the receiver operating characteristic curve and precision-recall curve. We performed an incidence-free survival analysis for a period of 30 years following the ECG stratified by model predictions. To simulate real-world deployment, we trained a separate model using all ECGs before 2010 and evaluated model performance on a test set of ECGs from 2010 through 2014 that were linked to our stroke registry. We identified the patients at risk for AF-related stroke among those predicted to be high risk for AF by the model at different prediction thresholds.

Results:

The area under the receiver operating characteristic curve and area under the precision-recall curve were 0.85 and 0.22, respectively, for predicting new-onset AF within 1 year of an ECG. The hazard ratio for the predicted high- versus low-risk groups over a 30-year span was 7.2 (95% CI, 6.9–7.6). In a simulated deployment scenario, the model predicted new-onset AF at 1 year with a sensitivity of 69% and specificity of 81%. The number needed to screen to find 1 new case of AF was 9. This model predicted patients at high risk for new-onset AF in 62% of all patients who experienced an AF-related stroke within 3 years of the index ECG.

Conclusions:

Deep learning can predict new-onset AF from the 12-lead ECG in patients with no previous history of AF. This prediction may help identify patients at risk for AF-related strokes.
Clinical Characteristics and In-Hospital Outcomes of Varying Definitions of Minor Stroke
Authors: Xiong Yunyun , Gu Hongqiu , Zhao Xing-Quan , Yang Xin , Wang Chunjuan , Wang Yi-Long , Liu Li-Ping , Zhou Qi , Fisher Marc , Li Zixiao , Wang Yongjun
Published: February 2021

Background and Purpose:

A variety of definitions for minor stroke have been proposed. We aimed to compare the clinical characteristics and outcomes of minor stroke defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 versus ≤3.

Methods:

We retrieved acute ischemic stroke patients with NIHSS score ≤5 in the CSCA study (China Stroke Center Alliance) between August 2015 and 2019. In-hospital clinical outcomes including all-cause mortality, stroke, and myocardial infarction were compared between the NIHSS score ≤5 and NIHSS score ≤3 groups using absolute standardized differences (ASD).

Results:

A total of 1 006 798 patients were registered in the CSCA program from 1476 hospitals, 472 352 patients had NIHSS score ≤5, of whom 356 314 patients had NIHSS score ≤3. The in-hospital composite events of death, myocardial infarction, or recurrent stroke were not significantly different between the NIHSS score ≤5 and NIHSS score ≤3 groups (5.6% [26 346/472 352] versus 5.2% [18 682/356 314]; ASD, 1.8). The in-hospital all-cause mortality (0.1% [443/472 352] versus 0.1% [255/356 314]; ASD, <0.01), recurrent ischemic stroke (5.3% [25 026/472 352] versus 5.0% [17 777/356 314]; ASD, 1.4), and hemorrhagic stroke (0.5% [2151/472 352] versus 0.4% [1475/356 314]; ASD, 1.5) were not significantly different between both the NIHSS score ≤5 and NIHSS score ≤3 groups.

Conclusions:

Our large-scale study identified that minor stroke using NIHSS scores ≤5 and ≤3 as the definition was comparable with each other regarding in-hospital all-cause mortality, recurrent stroke, and hemorrhagic stroke. This observation may be useful for future comparison studies and clinical trial design.
Penitence and Crusade in the Assumption Chapel of the Real Monasterio de Las Huelgas, Burgos
Authors: Streit Jessica Renee
Published: February 2021

This study aims to interpret the visual qualities of the Assumption Chapel, located in the Cistercian monastery of Santa Maria La Real de Las Huelgas, Burgos. Rejecting the “mudejar” paradigm often used to explain the chapel’s connections to Andalusi architecture, the article instead considers its relationships to a group of twelfth- and thirteenth-century domed churches in Iberia and the French Pyrenees, as well as to Las Huelgas’s adjacent, late-Romanesque cloister. In so doing, it situates the Assumption Chapel in a broader context of monuments related to penitence and crusade in the Holy Land and Iberia. It also considers the chapel’s form and function in the light of Las Huelgas’s ritual topography. Most broadly, this study shows how seemingly incongruent visual languages—in this case Romanesque and Andalusi—can comprise a coherent program of imagery.
Legal Intervention in Planning Regulations: Cooper v Wandsworth in a West African Context.
Authors: Mensah Kwadwo B.
Published: February 2021

One of the most important problems facing many West African cities in recent times is rapid and seemingly uncontrollable urbanization. The enormous pressure which these developments have had on public systems in general - sanitation, sewage, housing, health care and transport, has forced many cities to think of innovative ways of handling these crisis. Planning departments with substantial expertise in urban problems, are being set up or are being re-organized to meet these new challenges. The powers that planning departments have, and their impact on the lives of ordinary citizens cannot be over-estimated. To prevent abuse of power and to make them responsive to the needs of citizens, several methods are used to control them. Judicial review of administrative actions is the legal method used to control many public bodies in English speaking West African countries.

In this article, I shall argue that in spite of its strengths, there is a general tendency to use judicial review to protect common law values like individual proprietary rights against the claims of state institutions. In West Africa, because of the weakness of public institutions, the intervention of the law, while protecting important private rights may hamper administrative effectiveness. Anticipating the use of the leading English case, Cooper v Wandsworth2 in reviewing planning decisions in West Africa, I shall conclude that such a position may not only diminish administrative effectiveness, but it may also diminish property rights.
Les Sous-Regions Rurales de la Province Orientale Dans la Dynamique de L’histoire Recente du Zaire: De 1960 à 1985 (Cas Du Bas-Uélé)
Authors: Dieudonné Mily Denda-Sakala
Published: February 2021

The Rural Sub-Regions of the East-Province in the Recent Historical Dynamics of Zaïre: from 1960 to 1985 (The Case of the Bas-Uélé)

This study takes the Sub-Region of the Bas-Ulélé as an example of the recent history of the rural areas in Zaire. It gives a description from an insider’s point of view based on local research, results in a testimony relating the complete deterioration of rural potentialities in Zaire.

The article describes how in the first years after independence, the rich natural resources and the colonial infrastructure brought prosperous development. From 1964 to 1966, however, the Simba-rebellion ravaged the area, destroying a great deal of the infrastructure and caused large-scale massacres among the local population.

After the crushing of the rebellion, the subsequent revival was quickly halted by constant bureaucratic hindrances and interference from Mobutu’s MPR. “Zairisation” led to farther deterioration of the economic infrastructure.

From 1980 on, the Sub-Region was neglected more and more by the central government and even by its elected representatives. Finally, the liberalising of gold-prospecting withdrew farmers, schoolchildren and teachers form their normal activities leading only to more misery in the area.
Definition de L’adjectif en Langues Bantu
Authors: Baka Jean
Published: February 2021

Definition of the Adjective in Bantu Languages

In Bantu, as in other language groups, the definition of the adjective depends on the type of criteria that one uses. Some authors make use of morphological criteria, some of syntactic criteria and others of semantic criteria. From this variety of criteria there follows a diversity of definitions. One can reach, nevertheless, a more appropriate definition, by having recourse to the whole set of possible criteria but giving primacy to the syntactic ones. Such definition allows us – on the one hand – to bypass the dichotomy between nouns and pronouns which is founded on a purely morphological criterion « the form of the prefix » and – on the other hand – to restrict the meaning of the word 'adjective' to a purely semantic notion.
De Daasanech van Zuid-West Ethiopië: Begrippen Rond Welzijn en Tegenspoed
Authors: Houtteman Yvan
Published: February 2021

The Daasanech of South-Western Ethiopia: Concepts Around Prosperity and Misfortune

The question that is taken up in this lecture is how models which deal with prosperity and misfortune and with sickness and health are related to action-models of restoration and defence. I try to illuminate the connections between the experience of cosmos, body and social world, between rituals and the prosperity of the individual and his social group. Misfortune is always a consequence of a broken relationship between man and the social and cosmic order. As such, it can be seen as a "magical" punishment because of “wrong” behaviour. To restore health is to take away the punishment through appropriate action in which both the offender and the victim (or his social group) are involved. Starting from a short explication of the social, cosmic and bodily models, I concentrate on the concepts that deal with the causes of sickness and infertility and focus on some of the principles that shape the restoration-rituals.
Medias et Imperialisme Culturel: Le cas du Burkina Faso
Authors: Théophile Balima Serge
Published: February 2021

Media and Cultural Imperialism in Burkina Faso

The various kinds of information released in the press and other media are cultural products that partake in the shaping of citizens' opinions and minds. Radio and television in particular present their audiences in Burkina Faso with various life-styles through diverse entertainment programmes which have grown popular among the urban population. These are fertile fields for cultural imperialism in the country. In the on-going process of internationalization of culture facilitated by the new communication technology, the cultural identity of Africans is increasingly threatened. This phenomenon is the result of adverse political and economic conditions with significant cultural consequences. In the long run, these cultural consequences will lead to the marginalization of Africa on the international scene and its increased dependence on the western powers.
Taiwan Rainbands Formed in the Outer Region of Tropical Cyclones
Authors: Lin Che-Yu , Yu Cheng-Ku
Published: February 2021

This study used Doppler radar data, surface observations, and National Centers for Environmental Prediction reanalysis data to explore the statistical characteristics of Taiwan rainbands (TRs) that formed in the outer region of tropical cyclones (TCs). A comprehensive examination of the available radar measurements from 2002 to 2017 identified a total of 103 TRs from 44 TC events and showed that approximately 47% of all TCs influencing Taiwan could develop TRs. The spatial distribution of TR formation exhibited a substantial offshore extent, with the highest frequency observed ~25–100 km offshore. The TRs tended to be initiated when the northwestward-moving typhoons passed over the oceanic area northeast of Luzon Island (16°–20°N, 122°–127°E), the Philippines. This track characteristic brought stronger easterly onshore flow to the eastern coast of Taiwan and favored the development of a pronounced coastal pressure ridge. In particular, the offshore convergence caused by upstream deceleration of the onshore flow due to orographic blocking was found to be a primary contributor to the initiation of the TRs. The strength of the observed coastal pressure ridge and its high correlation with the intensity of environmental onshore flow associated with outer circulations of TCs were consistent with the theoretical prediction of pressure distributions generated as incident flow interacted dynamically with the Taiwan topography. Results from the study suggest that the typhoon location relative to the Taiwan landmass is a critical factor determining TR initiation.
“This Is Not the Hill to Die on. Even if We Literally Could Die on This Hill”: Examining Communication Ecologies of Uncertainty and Family Communication About COVID-19
Authors: Hernandez Rachael A. , Colaner Colleen
Published: February 2021

As information about the public health risks surrounding COVID-19 continues to shift over time, families communicate to navigate this ongoing uncertainty. For example, families must interpret inconsistent media and public health messages about COVID-19, which may in turn have implications for health risk behavior. Adding to this complexity, household structures and routines are adapting in response to COVID-19. Adult family members in some families may suddenly experience extreme physical proximity, while others must coordinate to make decisions about their health and prevention behaviors while maintaining physical distance. Furthermore, members of these families must balance relational maintenance while communicating to assess and avoid health risks. The ongoing ambiguity of information about COVID-19 means that these relational processes must be managed in the midst of chronic uncertainty. The current study uses semistructured interviews and interpretive analysis to understand how adult children (aged 23-51 years) manage chronic uncertainty about COVID-19 in communication with their parents. Findings explore themes of navigating information about COVID-19 risks and protections, managing uncertainty management about media and political messages, and accepting time-related uncertainties.
The use of routine blood tests to assist the diagnosis of COVID-19 in symptomatic hospitalized patients
Authors: Parsons IT , Parsons AT , Balme E , Hazell G , Gifford R , Stacey M , Woods DR , Russell-Jones D
Published: February 2021

Introduction

Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19.

Method

A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient’s clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation.

Results

Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of –0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR.

Discussion

Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.
Large-Sample Variance of Fleiss Generalized Kappa
Authors: Gwet Kilem L.
Published: February 2021

Cohen’s kappa coefficient was originally proposed for two raters only, and it later extended to an arbitrarily large number of raters to become what is known as Fleiss’ generalized kappa. Fleiss’ generalized kappa and its large-sample variance are still widely used by researchers and were implemented in several software packages, including, among others, SPSS and the R package “rel.” The purpose of this article is to show that the large-sample variance of Fleiss’ generalized kappa is systematically being misused, is invalid as a precision measure for kappa, and cannot be used for constructing confidence intervals. A general-purpose variance expression is proposed, which can be used in any statistical inference procedure. A Monte-Carlo experiment is presented, showing the validity of the new variance estimation procedure.
Prediction of breakthrough extruding force in large-scale extrusion process using artificial neural networks
Authors: Wei Wei , Yuan Chaolong , Wu Rendong , Jiao Wei
Published: February 2021

Accurate prediction of breakthrough extruding force is very important for extrusion production, especially for the large-scale extrusion process, which directly affects the production costs and safety. In this paper, based on the production data of the 360-million-newton-tonnage extruding machine, an artificial neural network (ANN) algorithm is used to establish the breakthrough extruding force prediction model for the large-scale extrusion process, and the calculation results are validated. Results show that the proposed model has high accuracy, and the average relative error between the predicted and experimental values is only 1.79%. Further, problems that are difficult to quantitative analyze such as die wear and glass powder residue in actual production, which can be regarded as “noises,” are studied. Finally, the model presented is compared with the traditional finite element (FE) model. The accuracy of the ANN model is 10.2 times that of the FE model. Thus, the model established in the study fully considers the difference between actual production and theoretical analysis and provides an effective method for accurately predicting the breakthrough extruding force.
Mini Review: The Last Mile—Opportunities and Challenges for Machine Learning in Digital Toxicologic Pathology
Authors: Turner Oliver C. , Knight Brian , Zuraw Aleksandra , Litjens Geert , Rudmann Daniel G.
Published: February 2021

The 2019 manuscript by the Special Interest Group on Digital Pathology and Image Analysis of the Society of Toxicologic pathology suggested that a synergism between artificial intelligence (AI) and machine learning (ML) technologies and digital toxicologic pathology would improve the daily workflow and future impact of toxicologic pathologists globally. Now 2 years later, the authors of this review consider whether, in their opinion, there is any evidence that supports that thesis. Specifically, we consider the opportunities and challenges for applying ML (the study of computer algorithms that are able to learn from example data and extrapolate the learned information to unseen data) algorithms in toxicologic pathology and how regulatory bodies are navigating this rapidly evolving field. Although we see similarities with the “Last Mile” metaphor, the weight of evidence suggests that toxicologic pathologists should approach ML with an equal dose of skepticism and enthusiasm. There are increasing opportunities for impact in our field that leave the authors cautiously excited and optimistic. Toxicologic pathologists have the opportunity to critically evaluate ML applications with a “call-to-arms” mentality. Why should we be late adopters? There is ample evidence to encourage engagement, growth, and leadership in this field.
Effect of formalin fixation on measured concentrations of deposited gadolinium in human tissue: an autopsy study
Authors: Hasegawa Makoto , Marshall Desiree A , Gonzalez-Cuyar Luis F , Hippe Daniel S , Samy Shar , Maravilla Kenneth R
Published: February 2021

Background

Generally, studies of gadolinium (Gd) deposition in humans measure concentration by analyzing formalin fixed postmortem tissue. However, the effect of formalin fixation on measured Gd concentration has not been well investigated.

Purpose

To evaluate the effect of fixation by comparing Gd concentration in fresh versus formalin-fixed postmortem human tissues.

Material and Methods

Fresh samples of bone and skin were collected from autopsy cases with previous exposure to Gd-based contrast agents (GBCAs). The type of GBCA administered, dose, and estimated glomerular filtration rate were recorded. Each tissue sample was cut into three aliquots. Paired samples were stored fresh frozen while the remaining two were stored in 10% neutral buffered formalin for one and three months, respectively. Gd concentration was measured using ICP-MS.

Results

Of 18 autopsy cases studied, 12 were exposed to only macrocyclic GBCA, one to only linear agents, and five received both macrocyclic and linear agents. On average, Gd concentration for bone decreased 30.7% after one month of fixation ( P = 0.043) compared to non-fixed values. There was minimal, if any, change in concentration between one and three months (average decrease 1.5%; P = 0.89). The findings were numerically similar for skin tissue with an average decrease of 36.9% after one month ( P = 0.11) and 6.0% ( P = 0.73) between one and three months.

Conclusion

Formalin fixation appears to decrease Gd concentration in bone and skin by approximately 30%–40% on average. The largest decrease occurs within the first 30 days of fixation followed by a considerably smaller decrease at 60 days.
Melanosis Coli in Pigs Coincides With High Sulfate Content in Drinking Water
Authors: Rodríguez-Gómez Irene M. , Gómez-Laguna Jaime , Ruedas-Torres Inés , Sánchez-Carvajal José M. , Garrido-Medina Ángel V. , Roger-García Gabino , Carrasco Librado
Published: February 2021

Melanosis coli is a well-described condition in humans, characterized by the accumulation of lipofuscin-laden macrophages in the lamina propria of the colon, giving it a dark tone. An increased apoptosis rate of colonic epithelial cells appears to be the underlying pathogenesis. In pigs, oxidative damage has been proposed as one of the causes for melanosis coli. In this article, we report a series of cases of melanosis coli in pigs affecting several finishing units in the south of Spain. Large intestines had dark green to brown pigmentation of the mucosa. Histological, histochemical, and ultrastructural studies confirmed a high number of lipofuscin-laden macrophages in the lamina propria of the rectum and colon, which additionally stained positive for the apoptosis marker cleaved caspase-3. Of note, all affected finishing units utilized water supply with a high content of sulfates, which may be one of the causes for melanosis coli development in pigs.
Enhancing mechanical properties of consolidated nanocrystalline copper powder by means of equal channel angular pressing method
Authors: Gode Ceren
Published: February 2021

Ultrafine grained and nanostructured materials have drawn significant attention due to their unusual mechanical behavior. The purpose of this research was to study the mechanical properties and microstructural evolution of nanocrystalline copper obtained through a bottom-up procedure of nanoparticle consolidation by equal channel angular pressing (ECAP). ECAP was approved to be a proper approach to produce comparatively big nanocrystalline consolidates including acceptable mechanical properties. The effects of ECAP pass numbers on consolidation achievement were also assessed. The quite large strains observed in the samples were associated with the bimodal distribution condition of grain sizes. The present work reveals that ECAP consolidation of nanoparticles presents a novel opportunity to investigate the mechanical response of nanostructured metals and alloys moreover it gives a chance to the production of unique kinds of bulk materials for useful purposes.
Procedural fairness: Between human rights law and social psychology
Authors: Graaf Cathérine Van de
Published: February 2021

Fair procedures have long been a topic of great interest for human rights lawyers. Yet, few authors have drawn on research from other disciplines to enrich the discussion. Social psychological procedural justice research has demonstrated in various applications that, besides the final outcome, the manner in which one’s case is handled matters to people as well. Such research has shown the impact of procedural justice on individuals’ well-being, their acceptance of unfavourable decisions, perceptions of legitimacy and public confidence. The ECtHR has confirmed the desirability of these effects in its fair trial jurisprudence. Thus far, it remains unclear to what extent the guarantees offered by Article 6(1) of the European Convention on Human Rights (the right to a fair trial) coincide with the findings of empirical procedural justice research. This article aims to rectify this and uncover similarities between the two disciplines.
Price and subsidy under uncertainty: Real-option approach to optimal investment decisions on energy storage with solar PV
Authors: Qu Jingyu , Jeon Wooyoung
Published: February 2021

Renewable generation sources still have not achieved economic validity in many countries including Korea, and require subsidies to support the transition to a low-carbon economy. An initial Feed-In Tariff (FIT) was adopted to support the deployment of renewable energy in Korea until 2011 and then was switched to the Renewable Portfolio Standard (RPS) to implement more market-oriented mechanisms. However, high volatilities in electricity prices and subsidies under the RPS scheme have weakened investment incentives. In this study we estimate how the multiple price volatilities under the RPS scheme affect the optimal investment decisions of energy storage projects, whose importance is increasing rapidly because they can mitigate the variability and uncertainty of solar and wind generation in the power system. We applied mathematical analysis based on real-option methods to estimate the optimal trigger price for investment in energy-storage projects with and without multiple price volatilities. We found that the optimal trigger price of subsidy called the Renewable Energy Certificate (REC) under multiple price volatilities is 10.5% higher than that under no price volatilities. If the volatility of the REC price gets doubled, the project requires a 26.6% higher optimal investment price to justify the investment against the increased risk. In the end, we propose an auction scheme that has the advantage of both RPS and FIT in order to minimize the financial burden of the subsidy program by eliminating subsidy volatility and find the minimum willingness-to-accept price for investors.
An adaptive seamless Phase 2-3 design with multiple endpoints
Authors: Jin Man , Zhang Pingye
Published: February 2021

Adaptive seamless Phase 2-3 design has been considered as one possible way to expedite development time for a drug program by allowing the expansion from an ongoing Phase 2 trial into a Phase 3 trial. Multiple endpoints are often tested when a regulatory approval is pursued. Here we propose an adaptive seamless Phase 2-3 design with multiple endpoints which can expand an ongoing Phase 2 trial into a Phase 3 trial based on an intermediate endpoint for adaptive decision and test the endpoints with a powerful multiple test procedure. It is proved that the proposed design can preserve the familywise Type I error under a mild assumption that is expected to hold in practical considerations. We illustrate our proposed design with an example trial design for oncology. Simulations are conducted to confirm the control of the familywise Type I error and the adaptive seamless Phase 2-3 design is illustrated with an example.
After He Jianku: China's biotechnology regulation reforms
Authors: Song Lingqiao , Joly Yann
Published: February 2021

The unveiling of the world’s first gene-edited twins by biophysics researcher He Jiankui generated much discussion about Chinese legal and ethical frameworks for biotechnology. In response, the highest Chinese legislative body, the National People’s Congress, and the two responsible departments for biotechnology, the Ministry of Science and Technology and the National Health Committee, have undertaken a seemingly far-reaching regulatory reform. The most salient step of this reform is to regulate genetic research and human embryo research in the Chinese Civil Code. This article overviews recent policy developments in China and their respective importance for promoting a governance framework for biomedical research that meets the expectations of the international community. However, this regulatory reform could also set stricter administrative procedures in place for Chinese institutions and their foreign partners, which may impede scientific progress. The concrete impact of this reform on the practice of Chinese scientists will need to be closely scrutinised by Chinese authorities and the international community.
Towards a Comprehensive Index of Labour Law Reform and Ranking of States
Authors: Dasgupta Bhaskar
Published: February 2021

Since the pioneering paper by Besley and Burgess (2004) claimed to have found a positive relationship between flexible and pro-employer labour regulations with manufacturing sector performance, there has been an increasing pitch among policymakers to rationalise India’s complicated labour laws. Several state governments have since undertaken significant reforms in their respective labour law regimes. During the recent pandemic-induced lockdown, some states have gone to the extent of temporarily suspending labour laws to kick-start the economy. The Government of India has also recently consolidated the fragmented labour laws by integrating them into four functionally arranged Codes. But the regulatory measure developed by Besley and Burgess, the very basis of their conclusions, has been criticised on the ground of narrow coverage, methodological inconsistency, misclassification of amendments, etc. This article, therefore, attempts to construct a comprehensive Index by mapping state level-amendments in five important labour legislations over the seven-decade period from 1949 to 2017 and coding those amendments. The article is organised as follows: After the context-setting introductory section, the second section summarises the existing evidence on the relationship between labour regulations and manufacturing sector performance in India. The third section discusses the limitations of Besley–Burgess Index. The fourth section briefly mentions the research direction post publication of Besley–Burgess paper. The fifth section develops a comprehensive Index, and it discusses how it improves the BB Index. The sixth section concludes the article.

JEL: J3, K3
Reflections on Chambers’ Odyssey
Authors: Whittington Geoffrey
Published: February 2021

This is a series of critical reflections on the contribution of Raymond J. Chambers to accounting thought, education and practice. It was stimulated by the recent publication of Accounting Thought and Practice Reform: Ray Chambers’ Odyssey, by Frank Clarke, Graeme Dean and Martin Persson, and draws extensively on the material presented in that book. It represents the author’s personal reflections on the material in The Odyssey rather than a comprehensive survey of the extensive literature surrounding Chambers’ work.
Health Behavior Change Processes Among Adults With Serious Mental Illness Engaged in Illness Self-Management
Authors: Muralidharan Anjana , Peeples Amanda , Lucksted Alicia
Published: February 2021

Self-management interventions promote illness management among adults with chronic health conditions. Little is known regarding the processes by which these interventions have their effects. The present study examined how Living Well, an effective self-management intervention for adults with serious mental illness, led to health behavior change in a randomized controlled trial. A convenience subset ( N = 15) of participants completed qualitative interviews regarding the feasibility/acceptability of Living Well. An inductive secondary qualitative analysis, using a combination of interpretive phenomenological and social constructivist approaches, was conducted to examine processes of change. Results indicate that Living Well provided information and knowledge, opportunities for learning from others and real-world practice, and an interpersonally supportive environment. These active ingredients led to enhanced self-awareness, confidence, sense of control, and behavior and health status changes among participants. These findings are considered in the context of prominent behavior change theories such as social cognitive theory and self-regulation.
Building Support for Place-Based Solutions to Childhood Obesity: Findings From Missouri
Authors: Calise Tamara Vehige , Ryder Amanda , Spezeski Jenette , Tong Katherine , Spitzer Natalie , Hatcher Ashley
Published: February 2021

Background

Place-based efforts offer promise in reducing childhood obesity. Yet, lack of public demand and support may hinder implementation.

Aims

This study aimed to assess whether the emphasis on place-based solutions, community-wide strategies, and multisector engagement in the Healthy Schools Healthy Communities (HSHC) initiative would shift public views on obesity including the need for greater public involvement and an increase in awareness and support for strategies.

Method

As part of the evaluation, two surveys were conducted—in 2014 and 2016—to examine the relationship between HSHC strategies and changes in public perception, support, and awareness of obesity. Both surveys were cross-sectional and conducted with a randomized sample of households.

Results

Most respondents indicated that parents/family (84.3% in 2014; 87.8% in 2016) and children (70.9% in 2014; 74.8% in 2016) had a large/very large responsibility for addressing childhood obesity. A higher percentage of 2016 respondents indicated willingness to work with others to increase availability of healthy foods (71.3% vs. 64.2%, respectively; p = .0280) and increase the number of places to be physically active in their community (71.1% vs. 60.7%, respectively; p = .0015).

Discussion

Findings suggest awareness and support of place-based efforts and willingness to engage may help garner ongoing support. However, individuals and families are still perceived as primarily responsible for addressing childhood obesity. Countering this mindset remains an ongoing challenge.

Conclusion

Streamlined messaging regarding the issue and associated solutions, enhanced skills and capacity to implement these efforts, and citizen engagement to garner support for place-based initiatives are important.
Non-nutritive sucking habits in a child: A clinical protocol to their prevention and management
Authors: Shah Rupal , Ashley Paul , Amlani Maya , Noar Joseph
Published: February 2021

Patients presenting with anterior open bites can be challenging to manage. This paper discusses the clinical features and aetiology of anterior open bites caused by non-nutritive sucking habits in a young child. It explores how these should be recognised and how certain interventions can be effective in their management. Whilst further high quality research is needed into the different methods and their effectiveness, the aim of the article is to provide a practical guide for general dental practitioners, orthodontists and paediatric dentists, who are involved in monitoring the developing dentitions of these patients.
A numerical study of the effects of oxy-fuel combustion under homogeneous charge compression ignition regime
Authors: Mobasheri Raouf , Aitouche Abdel , Peng Zhijun , Li Xiang
Published: February 2021

The European Union (EU) has recently adopted new directives to reduce the level of pollutant emissions from non-road mobile machinery engines. The main scope of project RIVER for which this study is relating is to develop possible solutions to achieve nitrogen-free combustion and zero-carbon emissions in diesel engines. RIVER aims to apply oxy-fuel combustion with Carbon Capture and Storage (CCS) technology to eliminate NOx emissions and to capture and store carbon emissions. As part of this project, a computational fluid dynamic (CFD) analysis has been performed to investigate the effects of oxy-fuel combustion on combustion characteristics and engine operating conditions in a diesel engine under Homogenous Charge Compression Ignition (HCCI) mode. A reduced chemical n-heptane-n-butanol-PAH mechanism which consists of 76 species and 349 reactions has been applied for oxy-fuel HCCI combustion modeling. Different diluent strategies based on the volume fraction of oxygen and a diluent gas has been considered over a wide range of air-fuel equivalence ratios. Variation in the diluent ratio has been achieved by adding different percentages of carbon dioxide for a range from 77 to 83 vol.% in the intake charge. Results show that indicated thermal efficiency (ITE) has reduced from 32.7% to 20.9% as the CO2 concentration has increased from 77% to 83% at low engine loads while it doesn’t bring any remarkable change at high engine loads. It has also found that this technology has brought CO and PM emissions to a very ultra-low level (near zero) while NOx emissions have been completely eliminated.
Law’s response to New Zealand’s ‘darkest of days’
Authors: Ip John
Published: February 2021

This article discusses various aspects of the New Zealand legal system’s response to the 15 March Christchurch mosques attack. It also considers New Zealand’s response to the attack from the perspective of the academic literature on the policymaking process and argues that the response to date has been modest and cannot be characterised as a knee-jerk reaction.