bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning Approaches to Determine Feature Importance for Predicting Infant Autopsy Outcome
Authors: Booth John , Margetts Ben , Bryant William , Issitt Richard , Hutchinson John Ciaran , Martin Nigel , Sebire Neil
Published: May 2020

Introduction: Sudden unexpected death in infancy (SUDI) represents the commonest presentation of postneonatal death, yet despite full postmortem examination (autopsy), the cause of death is only determined in around 45% of cases, the majority remaining unexplained. In order to aid counselling and understand how to improve the investigation, we explored whether machine learning could be used to derive data driven insights for prediction of infant autopsy outcome.
Methods: A paediatric autopsy database containing >7,000 cases in total with >300 variables per case, was analysed with cases categorised both by stage of examination (external, internal and internal with histology), and autopsy outcome classified as explained-(medical cause of death identified) or unexplained. For the purposes of this study only cases from infant and child deaths aged ≤ 2 years were included (N=3100). Following this, decision tree, random forest, and gradient boosting models were iteratively trained and evaluated for each stage of the post-mortem examination and compared using predictive accuracy metrics.
Results: Data from 3,100 infant and young child autopsies were included. The naive decision tree model using initial external examination data had a predictive performance of 68% for determining whether a medical cause of death could be identified. Model performance increased when internal examination data was included and a core set of data items were identified using model feature importance as key variables for determining autopsy outcome. The most effective model was the XG Boost, with overall predictive performance of 80%, demonstrating age at death, and cardiovascular or respiratory histological findings as the most important variables associated with determining cause of death.
Conclusion: This study demonstrates the feasibility of using machine learning models to objectively determine component importance of complex medical procedures, in this case infant autopsy, to inform clinical practice. It further highlights the value of collecting routine clinical procedural data according to defined standards. This approach can be applied to a wide range of clinical and operational healthcare scenarios providing objective, evidence-based information for uses such counselling, decision making and policy development.
Identification of DNA response elements regulating expression of CCAAT/enhancer-binding protein (C/EBP) β and δ during early adipogenesis
Authors: Merrett James E. , Bo Tao , Psaltis Peter J. , Proud Christopher G.
Published: May 2020

Given the high and increasing prevalence of obesity and associated disorders, such as type-2 diabetes, it is important to understand the mechanisms that regulate lipid storage and the differentiation of fat cells, a process termed adipogenesis. Using the well-established mouse 3T3-L1in vitromodel of adipogenesis, we refine how the induction of two key adipogenic transcription factors, CCAAT/enhancer-binding proteins (C/EBPs) β and δ are regulated during early adipogenesis. We identify, in the gene promoters ofCebpbandCebpd, the DNA response elements responsible for binding transcription factors that are activated by cAMP or glucocorticoids. We also show that mitogen-activated protein kinase (MAPK)-interacting kinase 2 (MNK2;Mknk2), which plays a distinct role in diet-induced obesity, is induced during early adipogenesis and identify the functional DNA response elements responsible for regulating its expression.Mknk2expression is maintained in differentiated 3T3-L1 adipocytes and is expressed at high levels across a range of mouse adipose tissue depots. Together, these new insights help to clarify the transcriptional program of early adipogenesis and identifyMknk2as one of potentially many genes up-regulated during adipogenesis.
A novel therapeutic antibody screening method using bacterial high-content imaging reveals functional antibody binding phenotypes ofEscherichia coliST131
Authors: Maes Mailis , Dyson Zoe A. , Smith Sarah E. , Goulding David A. , Ludden Catherine , Baker Stephen , Kellam Paul , Reece Stephen T. , Dougan Gordon , Scott Josefin Bartholdson
Published: May 2020

The increase of antimicrobial resistance (AMR), and lack of new classes of licensed antimicrobials, have made alternative treatment options for AMR pathogens increasingly attractive. Recent studies have demonstrated anti-bacterial efficacy of a humanised monoclonal antibody (mAb) targeting the O25b O-antigen ofEscherichia coliST131. To evaluate the phenotypic effects of antibody binding to diverse clinicalE. coliST131 O25b bacterial isolates in high-throughput, we designed a novel mAb screening method using high-content imaging (HCI) and image-based morphological profiling to screen a mAb targeting the O25b O-antigen. Screening the antibody against a panel of 86 clinicalE. coliST131 O25:H4 isolates revealed 4 binding phenotypes: no binding (18.60%), weak binding (4.65%), strong binding (69.77%) and strong agglutinating binding (6.98%). Impaired antibody binding could be explained by the presence of insertion sequences or mutations in O-antigen or lipopolysaccharide core biosynthesis genes, affecting the amount, structure or chain length of the O-antigen. The agglutinating binding phenotype was linked with lower O-antigen density, enhanced antibody-mediated phagocytosis and increased serum susceptibly. This study highlights the need to screen candidate mAbs against large panels of clinically relevant isolates, and that HCI can be used to evaluate mAb binding affinity and potential functional efficacy against AMR bacteria.
Solving the fractional heat-like and wave-like equations with variable coefficients utilizing the Laplace homotopy method
Authors: Nadeem Muhammad , Yao Shao-Wen
Published: May 2020

Purpose

This paper aims to suggest the approximate solution of time fractional heat-like and wave-like (TFH-L and W-L) equations with variable coefficients. The proposed scheme shows that the results are very close to the exact solution.

Design/methodology/approach

First with the help of some basic properties of fractional derivatives, a scheme that has the capability to solve fractional partial differential equations is constructed. Then, TFH-L and W-L equations with variable coefficients are solved by this scheme, which yields results very close to the exact solution. The derived results demonstrate that this scheme is very effective. Finally, the convergence of this method is discussed.

Findings

A traditional method is combined with the Laplace transform to construct this scheme. To decompose the nonlinear terms, this paper introduces the homotopy perturbation method with He’s polynomials and thus the solution is provided in the form of a series that converges to the exact solution very quickly.

Originality/value

The proposed approach is original and very effective because this approach is, to the authors’ knowledge, used for the first time very successfully to tackle the fractional partial differential equations, which are of great interest.
Design of a hybrid controller using genetic algorithm and neural network for path planning of a humanoid robot
Authors: Rath Asita Kumar , Parhi Dayal R. , Das Harish Chandra , Kumar Priyadarshi Biplab , Mahto Manjeet Kumar
Published: May 2020

Purpose

To navigate humanoid robots in complex arenas, a significant level of intelligence is required which needs proper integration of computational intelligence with the robot's controller. This paper describes the use of a combination of genetic algorithm and neural network for navigational control of a humanoid robot in given cluttered environments.

Design/methodology/approach

The experimental work involved in the current study has been done by a NAO humanoid robot in laboratory conditions and simulation work has been done by the help of V-REP software. Here, a genetic algorithm controller is first used to generate an initial turning angle for the robot and then the genetic algorithm controller is hybridized with a neural network controller to generate the final turning angle.

Findings

From the simulation and experimental results, satisfactory agreements have been observed in terms of navigational parameters with minimal error limits that justify the proper working of the proposed hybrid controller.

Originality/value

With a lack of sufficient literature on humanoid navigation, the proposed hybrid controller is supposed to act as a guiding way towards the design and development of more robust controllers in the near future.
Key factors for implementation and success of destination management systems. Empirical evidence from European countries
Authors: Martins Catarina Antónia , Carneiro Maria João Aibéo , Pacheco Osvaldo Rocha
Published: May 2020

Purpose

Destination management organizations perform a very important role regarding the management of tourism destinations. Destination management systems are a key technological infrastructure for these organizations. However, in the literature, it is not clear what are the factors that promote the implementation of these systems, neither what are the factors that contribute to their success. This study aims to propose and test two research models to overcome these research gaps.

Design/methodology/approach

The first model refers to the determinants of the implementation of destination management systems, and the second model refers to the determinants of the success of those systems. The models are tested with data collected through a questionnaire survey from destination management organizations of five European countries, which are among the leaders in international tourism receipts.

Findings

Concerning the factors that promote the implementation of destination management systems, this study reveals the importance of the diversity of partnerships that the private sector establishes in the destination, of advantages resulting from governance and of partners' involvement in the functions of destination management organizations. Concerning the factors that promote the success of these systems, this study highlights the importance of a phased implementation, the fact that a high number of functionalities in the system prevents success and the importance of having a revenue model that can support financial and operating costs.

Originality/value

The study provides important theoretical and practical contributions to the successful implementation of destination management systems by destination management organizations.
E-health system characteristics, medical performance and healthcare quality at UNRWA-Palestine health centers
Authors: Dahleez Khalid Abed , Bader Imad , Aboramadan Mohammed
Published: May 2020

Purpose

This study aims to investigate how e-health system characteristics (information quality, system quality, perceived ease of use, perceived usefulness) contribute to the enhancement of medical staff performance, patient care, and doctor–patient relationships at UNRWA-Gaza healthcare centers. It aims at testing an integrative single model comprising Technology Acceptance Model (TAM), D&M model and e-health system utilization.

Design/methodology/approach

This study followed the quantitative methodology and the deductive research approach. Data were collected from 241 medical staff who use the system employed in 19 different healthcare centers across the Gaza Strip. Partial least square/structural equation modeling technique was used to analyze the collected data and to test study hypotheses.

Findings

Study concluded that information quality of the adopted Health Information System (HIS) has both direct and indirect positive impact on staff performance, only direct positive impact on patient care and only positive indirect impact on doctor–patient relationship. System quality, on the other hand, was found to have negative direct impact and positive indirect impact on staff performance and has both direct and indirect positive impact on both doctor-patient relationship and patient care.

Research limitations/implications

Noteworthy that HIS has availability, speed and error detection and error prevention issues. It is recommended that these shortfalls be addressed together with improving user perception towards ease of use and usefulness of the system.

Practical implications

Management should also work to raise confidence in its medical staff to improve the effect of HIS on medical performance and patient care. It is also recommended that UNRWA should implement crowed management techniques such as queuing systems and on-phone booking to minimize patient waiting time.

Originality/value

The importance of the study stems from its context being conducted in a developing region (Gaza Strip-Palestine) which has a fragile economic, political and social environment with many other complexities. It is also conducted at United Nations Relief and Work Agency (UNRWA) healthcare centers, which provide medical services to Palestinian refugees. In addition, this study is among the few studies that address the impact of individual e-health success factors on both doctor-patient relationship and patient care constructs. Most previous studies concentrated on the impact of health system adoption as a whole on these two subject variables and one can hardly ever stop at studies that address effect of individual success factors on them. It also integrated both D&M system success model and TAM model with some additional amendments creating and tested a new model.
Williamson nanofluid flow through porous medium in the presence of melting heat transfer boundary condition: semi-analytical approach
Authors: Mishra S.R. , Mathur Priya
Published: May 2020

Purpose

Present investigation based on the flow of electrically conducting Williamson nanofluid embedded in a porous medium past a linearly horizontal stretching sheet. In addition to that, the combined effect of thermophoresis, Brownian motion, thermal radiation and chemical reaction is considered in both energy and solutal transfer equation, respectively.

Design/methodology/approach

With suitable choice of nondimensional variables the governing equations for the velocity, temperature, species concentration fields, as well as rate shear stress at the plate, rate of heat and mass transfer are expressed in the nondimensional form. These transformed coupled nonlinear differential equations are solved semi-analytically using variation parameter method.

Findings

The behavior of characterizing parameters such as magnetic parameter, melting parameter, porous matrix, Brownian motion, thermophoretic parameter, radiation, Lewis number and chemical particular case present result validates with earlier established results and found to be in good agreement. Finally reaction parameter is demonstrated via graphs and numerical results are presented in tabular form.

Originality/value

The said work is an original work of the authors.
Questionnaire‐based epidemiological study of hidradenitis suppurativa in Japan revealing characteristics different from those in Western countries
Authors: Hayama Koremasa , Fujita Hideki , Hashimoto Takashi , Terui Tadashi ,   The Japanese HS Research Group
Published: May 2020

Hidradenitis suppurativa (HS) is a chronic relapsing skin disease localized mainly on the apocrine gland‐bearing areas. In Japan, HS is yet to be fully understood, and no criteria have been established for its diagnosis or severity assessment. The purpose of this study was to investigate and characterize HS in Japan. We conducted a nationwide questionnaire‐based study, in which Japanese diagnostic criteria were proposed. Question items included age, sex, disease duration, past history, family history, smoking status, disease severity scores (Hurley stage, modified Sartorius score and Physician Global Assessment [PGA] score), treatments, comorbidities and prognosis. We analyzed 300 patients (219 males and 81 females) diagnosed with HS based on our criteria. Average disease duration was 92.3 ± 6.82 months. Only 12 (4%) patients had a family history of HS. Disease severity was classified by PGA score (mild, 100 [33.3%]; moderate, 133 [44.3%]; severe, 34 [11.3%]; most severe, 29 [9.7%]) and Hurley stage (I, 69 [23%]; II, 109 [36.3%]; III, 121 [40.3%]). Disease severities based on PGA score and Hurley stage were positively correlated to modified Sartorius score using the Kruskal–Wallis test (P < 0.001, respectively). Patients with diabetes mellitus showed higher PGA scores (χ2 = 10.977, P = 0.01185). Presence of axillary lesions related to higher PGA scores (χ2 = 8.6378, P = 0.03452). The results in this study and previous studies indicate that Japanese HS patients have different backgrounds from those in Western countries, and are characterized by male predominance, higher incidence of Hurley stages II and III, higher PGA scores in patients with axillary lesions and much fewer familial cases.
Three‐dimensional inversion of airborne data with applications for detecting elongated subvertical bodies overlapped by an inhomogeneous conductive layer with topography
Authors: Persova Marina G. , Soloveichik Yuri G. , Vagin Denis V. , Kiselev Dmitry S. , Grif Alexander M. , Koshkina Yulia I. , Sivenkova Anastasia P.
Published: May 2020

We propose the approach to 3D inversion of airborne electromagnetic data, which is intended for discovering subvertical bodies overlapped by essentially inhomogeneous conductive layers. The approach is based on the geometric inversion in which a geoelectrical medium is parameterized with the use of block structures. During the inversion, the coordinates of the borders between the blocks and the rows of the blocks as well as resistivities inside them are determined. In order to solve the forward problem of the airborne electromagnetic survey, we use the non‐conforming optimized mesh with the hexahedral cells, which enables us to reduce the number of degrees of freedom and smoothly approximate the curved borders of a geological medium. For a more reliable discovery of subvertical objects, we propose to carry out 3D inversions at several rotations of block structures relative to the flight lines. The workability of this approach is demonstrated using the data which are synthesized for complex geoelectrical models with topography, inhomogeneous overlapping layers and target subvertical bodies oriented differently relative to the flight lines. The results of this investigation show that, in some way or other, the elongated subvertical object is discovered and its orientation (the direction of its long side) is defined at different rotations of block structures used in 3D inversions. However, the most accurate recovery of the subvertical object length is achieved when the direction of its long side almost coincides with the direction of one of the block structures axes. Thus, the block structures rotations allow not only more reliably discovering a target object in complex geoelectrical conditions, but also more exactly defining its orientation and length.
Pubertal timing and adolescent delinquency†
Authors: Bucci Rebecca , Staff Jeremy
Published: May 2020

Early pubertal timing (PT) increases the risk of adolescent delinquency, whereas late development reduces this risk; however, the mechanisms explaining PT effects on delinquency remain elusive. Theoretically, the PT–delinquency relationship is as a result of changes in parental supervision, peer affiliations, and body‐image perceptions or is a spurious reflection of early life risk factors. Using intergenerational data from the Millennium Cohort Study, a prospective sample of children followed from infancy to age 14 years in the United Kingdom (N = 11,556 parent–child pairs), we find that for both boys and girls, early PT is associated with heightened risks of delinquency, relative to on‐time puberty, whereas late PT is associated with lower risks, even after controlling for a large share of childhood confounders. Mediation test results indicate that changes in parental supervision, peer affiliations, and body‐image perceptions from ages 11 to 14 partly account for associations between off‐time PT and delinquency. Our findings are most consistent with criminological theories in which the psychosocial, familial, and peer group changes that accompany off‐time pubertal development are emphasized. Changes in peer substance use, in particular, were the primary explanatory factor for the relationships between early and late PT and delinquency, for both boys and girls.
Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice
Authors: Roh Jason D. , Houstis Nicholas , Yu Andy , Chang Bliss , Yeri Ashish , Li Haobo , Hobson Ryan , Lerchenmüller Carolin , Vujic Ana , Chaudhari Vinita , Damilano Federico , Platt Colin , Zlotoff Daniel , Lee Richard T. , Shah Ravi , Jerosch‐Herold Michael , Rosenzweig Anthony
Published: May 2020

Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age‐related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24–30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age‐related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF.
Phosphatidylethanol Levels in Postpartum Women and Their Newborns in Uruguay and Brazil
Authors: Baldwin Aileen E. , Hayes Nicole , Ostrander Erika , Magri Raquel , Sass Nelson , dos Anjos Mesquita Maria , Martínez Monica , Juliani Monica Correa , Cabral Pablo , Fleming Michael
Published: May 2020

Background

There is increasing interest in the development of newborn screening tests to identify children at risk of fetal alcohol spectrum disorder (FASD) in order to provide these children with early intervention. Phosphatidylethanol (PEth) has emerged as a potential universal newborn screening candidate.

Methods

The aim of this report was to present the results of a study designed to compare PEth levels in 1,140 postpartum women and their newborn infants in Montevideo, Uruguay, and Sao Paulo, Brazil. Self‐report alcohol use during pregnancy data was collected, along with both maternal and newborn dried blood spot samples for PEth analysis.

Results

The average age and parity of the women in the sample were 26 years of age and 2.3 pregnancies. For the Uruguay sample (n = 611), 45.8% of postpartum women had PEth levels ≥ 8 ng/ml with a mean positive PEth of 43.6 ng/ml. In contrast, 86.8% of the newborns had PEth levels ≥ 8 ng/ml, with a mean positive PEth of 77.4 ng/ml. For the Brazil sample (n = 529), 33.2% of women had PEth levels ≥ 8 ng/ml with a mean positive PEth of 31 ng/ml. In contrast, 76.9% of the Brazil newborns had PEth levels ≥ 8 ng/ml and 43.9% with a mean positive PEth of 61.1 ng/ml. PEth levels were significantly higher in newborns compared with their postpartum mothers in both the Uruguay and Brazil samples. Self‐reported third‐trimester alcohol was 6% in the Uruguay sample and 9.1% in the Brazil sample compared with positive maternal PEth levels in 45.8% and 33.2%, respectively.

Conclusions

Clinicians may want to consider newborn PEth screening in high‐risk populations where prenatal alcohol use is common. The mechanism underlying significantly higher PEth levels in newborns compared with their mothers is not known.
Behavioural portfolio theory revisited: lessons learned from the field
Authors: Oehler Andreas , Horn Matthias
Published: May 2020

We examine the relation between households’ wealth and relative risk aversion (RRA) in two different frameworks: the Behavioural Portfolio Theory (BPT) and Merton’s consumption and portfolio choice model (CPCM). We apply the BPT to field data for the first time and show that the BPT provides a better fit than the CPCM to explain the financial risk‐taking of the households in Deutsche Bundesbank’s Panel on Household Finances survey. However, both models indicate decreasing RRA. While households’ education and financial literacy hardly improve the fit of either model, households show different risk‐taking behaviour in accordance with their self‐assessed risk attitude.
Different epigenome regulation and transcriptome expression of CD4+ and CD8+ T cells from monozygotic twins discordant for psoriasis
Authors: Li Xiaofang , Zhao Xincheng , Xing Jianxiao , Li Junqin , He Fusheng , Hou Ruixia , Wang Qiang , Yin Guohua , Li Xinhua , Zhang Kaiming
Published: May 2020

Objectives

Psoriasis is an immunodeficient skin disorder, and its exact pathogenesis is unclear. Monozygotic twins are presumed to be genetically identical, and their phenotypic differences may be due to transcriptional regulation or epigenome factors. To explain the inconsistency between twins, we have collected 3 pairs of monozygotic twins who are discordant for psoriasis.

Methods

Reduced representation of bisulfite sequencing and RNA sequencing was conducted using the peripheral blood of the twins to find the genes playing important roles in psoriasis pathogenesis.

Results

As a result, we found methylation diversity in four genes (MAST3, MTOR, PM20D1 and ZNF99), and we also found 9 differentially expressed genes (PPAN‐P2RY11, PIGV, RPS18, TMEM121, KIF21A, KCNH2, WNT10B, PRX and CDH24) by RNA sequencing. According to the conjoint analysis of methylation and the mRNA results, PTPN6, CCL5, NFATC1 and PRF1 were found to be closely related to psoriasis. We then annotated the genes to explore the associations between these genes and psoriasis.

Conclusions

These findings provide a better understanding of psoriasis that can improve the diagnosis and treatment of the disease.
‘Snail factors in testicular germ cell tumours and their regulation by the BMP4 signalling pathway’
Authors: Micati Diana J. , Radhakrishnan Karthika , Young Julia C. , Rajpert‐De Meyts Ewa , Hime Gary R. , Abud Helen E. , Loveland Kate L.
Published: May 2020

Background

Snail transcription factors mediate key cellular transitions in many developmental processes, including spermatogenesis, and their production can be regulated by TGF‐β superfamily signalling. SNAI1 and SNAI2 support many cancers of epithelial origin. Their functional relevance and potential regulation by TGF‐β superfamily ligands in germ cell neoplasia are unknown.

Methods

SNAI1, SNAI2 and importin 5 (IPO5; nuclear transporter that selectively mediates BMP signalling) cellular localization was examined in fixed normal adult human and/or neoplastic testes using in situ hybridization and/or immunohistochemistry. SNAI1 and SNAI2 functions were assessed using the well‐characterized human seminoma cell line, TCam‐2. Cell migration, adhesion/proliferation and survival were measured by scratch assay, xCELLigence and flow cytometry following siRNA‐induced reduction of SNAI1 and SNAI2 in TCam‐2 cells. The potential regulation of SNAI1 and SNAI2 in TCam‐2 cells by TGF‐β signalling ligands, activin A and BMP4 was evaluated following 48 hours culture, including with siRNA regulation of IPO5 to selectively restrict BMP4 signalling.

Results

In normal testes, SNAI1 transcript was identified in some spermatogonia and in spermatocytes, and SNAI2 protein localized to nuclei of spermatogonia, spermatocytes and round spermatids. In neoplastic testes, both SNAI1 and SNAI2 were detected in GCNIS and in seminoma cells. SNAI1 and SNAI2 reduction in TCam‐2 cells by siRNAs significantly inhibited migration and survival, respectively. Exposure to BMP4, but not activin A, significantly increased SNAI2 (~18‐fold). IPO5 inhibition by siRNAs decreased BMP4‐induced SNAI2 upregulation (~5‐fold). Additionally, SNAI2 reduction using siRNAs inhibited BMP4‐induced TCam‐2 cell survival.

Conclusions

This is the first evidence that SNAI1 and SNAI2 are involved in human spermatogenesis, with independent functions. These outcomes demonstrate that SNAI1 and SNAI2 inhibition leads to loss of migratory and viability capacities in seminoma cells. These findings show the potential for therapeutic treatments targeting SNAIL or BMP4 signalling for patients with metastatic testicular germ cell tumours.
Clinical course of coronavirus disease‐2019 in pregnancy
Authors: Pereira Augusto , Cruz‐Melguizo Sara , Adrien Maria , Fuentes Lucia , Marin Eugenia , Perez‐Medina Tirso
Published: May 2020

Introduction

The aim of this study is to report our clinical experience in the management of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during the first 30 days of the coronavirus disease (COVID‐19) pandemic.

Material and methods

We reviewed clinical data from the first 60 pregnant women with COVID‐19 whose care was managed at Puerta de Hierro University Hospital, Madrid, Spain from 14 March to 14 April 2020. Demographic data, clinical findings, laboratory test results, imaging findings, treatment received, and outcomes were collected. An analysis of variance (Kruskal‐Wallis test) was performed to compare the medians of laboratory parameters. Fisher's exact test was used to evaluate categorical variables. A correspondence analysis was used to explore associations between variables.

Results

A total of 60 pregnant women were diagnosed with COVID‐19. The most common symptoms were fever and cough (75.5% each) followed by dyspnea (37.8%). Forty‐one women (68.6%) required hospital admission (18 because of disease worsening and 23 for delivery) of whom 21 women (35%) underwent pharmacological treatment, including hydroxychloroquine, antivirals, antibiotics, and tocilizumab. No renal or cardiac failures or maternal deaths were reported. Lymphopenia (50%), thrombocytopenia (25%), and elevated C‐reactive protein (CRP) (59%) were observed in the early stages of the disease. Median CRP, D‐dimer, and the neutrophil/lymphocyte ratio were elevated. High CRP and D‐dimer levels were the parameters most frequently associated with severe pneumonia. The neutrophil/lymphocyte ratio was found to be the most sensitive marker for disease improvement (relative risk 6.65; 95% CI 4.1‐5.9). During the study period, 18 of the women (78%) delivered vaginally. All newborns tested negative for SARS‐CoV‐2 and none of them were infected during breastfeeding. No SARS‐CoV‐2 was detected in placental tissue.

Conclusions

Most of the pregnant women with COVID‐19 had a favorable clinical course. However, one‐third of them developed pneumonia, of whom 5% presented a critical clinical status. CRP and D‐dimer levels positively correlated with severe pneumonia and the neutrophil/lymphocyte ratio decreased as the patients improved clinically. Seventy‐eight percent of the women had a vaginal delivery. No vertical or horizontal transmissions were diagnosed in the neonates during labor or breastfeeding.
Controlled case series demonstrates how parents can be trained to treat paediatric feeding disorders at home
Authors: Taylor Tessa , Blampied Neville , Roglić Nikolas
Published: May 2020

Aim

Paediatric feeding disorders are normally managed by specialist clinics. We examined whether treatment gains were maintained when trained parents continued the programme at home and during meals out.

Methods

This controlled consecutive case series recruited 26 children (22 boys) with avoidant/restrictive food intake disorder, from a private paediatric feeding disorders practice in New South Wales, Australia. Their mean age was six (2‐13) years. All had severe feeding problems and mealtime skill deficits, and most had autism and developmental delays or intellectual disabilities. The children received intensive, individualised, behaviour‐analytic treatment for 11 (6‐21.5) days, and the parents were trained to continue it at home. The primary treatment outcomes included the range and amount of food eaten and mealtime behaviour.

Results

The children met all of the therapeutic goals agreed at the treatment outset. They ate a mean of 92 different foods and improved how they ate, drank and behaved during mealtimes. The mean differences before and after treatment were clinically and statistically significant, and the gains were maintained during follow‐up at a mean of 2.3 years. Parental satisfaction and treatment acceptability were high.

Conclusion

Specially trained parents successfully continued paediatric eating disorder treatment at home and maintained treatment gains.
Tomorrow Is Another Day: How Motives of Entrepreneurship Relate to the Pursuit of Business Growth
Authors: Prasastyoga Bramesada , van Leeuwen Esther , Harinck Fieke
Published: May 2020

Past research has suggested that small business growth plays an important role in economic growth. This paper presents three studies that examined the psychological process underlying the relationship between motives of entrepreneurship and business growth pursuit by focusing on the role of time perspective. The results from three studies (Study 1, N = 142, and Study 2, N = 181, mostly Western small‐business owners; Study 3,N = 254, Indonesian small‐business owners) demonstrated that opportunity‐based entrepreneurship was positively associated with business growth pursuit through increased future time perspective (Studies 1 to 3), whereas necessity‐based entrepreneurship was negatively associated with business growth pursuit through increased present time perspective and decreased future time perspective (Study 3). These findings help explain why some business owners avoid business growth by highlighting the vital role of time perspective in explaining why and how motives of entrepreneurship relate to the pursuit of business growth across social and cultural contexts.
English hepatitis C registry data show high response rates to directly acting anti‐virals, even if treatment is not completed
Authors: Drysdale Kathryn , Ntuli Yevedzo , Bestwick Jonathan , Gelson William , Agarwal Kosh , Forton Daniel , Mutimer David , Elsharkawy Ahmed M. , Townley Ceri , Mahomed Faizel , Foster Graham R.
Published: May 2020

Background

In England, choice of hepatitis C therapy is determined by national contracts that change with time, facilitating comparisons between different regimens. England has a diverse population with hepatitis C including large proportions of uncommon viral genotypes.

Aim

To evaluate efficacy of directly acting anti‐viral treatments for hepatitis C in England using real‐world data from the national treatment registry.

Methods

Sustained virological response (SVR) rates 12 weeks after treatment completion for patients treated between 2014 and August 2018 who attended for SVR tests were analysed in univariate subgroups using Chi‐squared tests. Multivariate models were constructed with clinically relevant variables to determine predictors of SVR and evaluate the impact of treatment regimens.

Results

SVR data were available on 14,603 treated patients. The overall SVR rate was 95.59% [95% CI 95.25%‐95.91%]. Multivariable regression modelling in patients with genotype 1 infection showed that the odds of SVR with elbasvir/grazoprevir were higher than for those treated with sofosbuvir/ledipasvir (OR 1.891, 95% CI 1.072‐3.336, P = 0.028). For genotype 3, we found no significant difference between any of the treatment regimens. Patients who completed at least one third of the planned treatment duration achieved SVR rates in excess of 80%.

Conclusions

All of the currently licensed hepatitis C direct‐acting anti‐viral regimens had similar efficacy (>95%) in an unselected population. Noncompletion of planned treatment duration still resulted in over 80% SVR rates provided that more than one third of treatment was completed.
Impact of persistence with tumour necrosis factor inhibitors on healthcare resource utilization and costs in chronic inflammatory joint diseases
Authors: Belhassen Manon , Tubach Florence , Hudry Christophe , Woronoff‐Lemsi Macha , Levy‐Bachelot Laurie , Van Ganse Eric , Fautrel Bruno
Published: May 2020

Aim

To assess persistence with subcutaneous (SC) tumour necrosis factor (TNF) inhibitors as well as the impact of persistence on healthcare resource utilization (HCRU) and costs in patients with chronic inflammatory joint diseases.

Methods

In this cohort study using population‐based French claims data (from 2011 to 2014), we measured persistence with SC TNF inhibitors within 12 months (M0‐12) following treatment initiation in treatment‐naïve and treatment‐experienced users (divided into three cohorts: rheumatoid arthritis [RA], ankylosing spondylitis [AS] and psoriatic arthritis [PsA]). Persistent patients were propensity score matched to nonpersistent patients at M12. The impact of persistence status on HCRU and costs was assessed during M12‐24.

Results

Of treatment‐naïve (n = 3,804) and treatment‐experienced (n = 2,279) users, only 56.1% and 46.8% were persistent at M12, respectively. Nonpersistent patients had more outpatient visits, computerized tomography scans, spine or joint magnetic resonance imaging procedures and disease‐related hospitalizations, while persistent patients had more rheumatologist visits. Nonpersistent patients had lower drug costs but higher nondrug‐related healthcare and hospitalization costs than persistent patients. In AS and PsA, overall healthcare costs were similar in persistent and nonpersistent patients. In RA, overall healthcare costs were lower in persistent patients (15,753€ vs 17,590€ in treatment‐naïve and 17,622€ vs 21,177€ in treatment‐experienced).

Conclusion

Persistence with SC TNF inhibitors within first 12 months following treatment initiation was low in both treatment‐naïve and treatment‐experienced patients. Differences were observed in distribution of costs between persistent and nonpersistent patients, showing that nonpersistence with SC TNF inhibitors can lead to increased HCRU and higher costs.
Challenges and opportunities to include patient‐centric product design in industrial medicines development to improve therapeutic goals
Authors: Timpe Carsten , Stegemann Sven , Barrett Andrew , Mujumdar Siddharthya
Published: May 2020

In the past, drug developers in industry chose approaches mainly focusing on the drug product's efficacy, safety and quality according to the level required by regulatory expectations stipulated in guidelines, pharmacopoeia and other regulatory provisions. By putting more focus on the patient perspective, regulatory authorities are currently raising their requirements regarding successful product submissions. The increasing involvement of patients in the product development process (e.g. conduction of human factor use tests, integration of feedback from patient and patient advisory groups into clinical programmes) requires adaptations to the existing and established industrial drug development processes without compromising fast patient access to innovative therapies. This review provides an expert opinion on the emerging challenges and opportunities to implement a patient‐centric approach into new drug development programmes. The aim is to better understand the challenge of finding the right balance between bringing innovative drugs fast to the patients and to develop these in parallel in a patient‐centric product form as well as why this is an opportunity and how stakeholder parties (e.g. patients, clinicians, pharmacists, caregivers, regulators) can provide support to achieve desired outcomes.
Normalization of serum B‐cell maturation antigen levels predicts overall survival among multiple myeloma patients starting treatment
Authors: Jew Scott , Chang Tiffany , Bujarski Sean , Soof Camilia , Chen Haiming , Safaie Tahmineh , Li Mingjie , Sanchez Eric , Wang Cathy , Spektor Tanya M. , Emamy‐Sadr Marsiye , Swift Regina , Rahbari Ashkon , Patil Saurabh , Souther Eric , Berenson James R.
Published: May 2020

Serum B‐cell maturation antigen (sBCMA) is a novel biomarker for B‐cell malignancies. A normal reference range (<82·59 ng/ml) has been recently established but the impact of achieving normal levels to outcomes for patients receiving treatment for B‐cell malignancies has not been studied. We first found that among multiple myeloma (MM) patients starting a new treatment, those who begin treatment within normal sBCMA limits (<82·59 ng/ml) have improved progression‐free survival (PFS; P = 0·0398) and overall survival (OS; P = 0·0217) than those who do not. Furthermore, among patients who begin treatment with elevated (≥82·59 ng/ml) sBCMA levels, we assessed the relationship of a decrease in sBCMA to the normal range to OS and found that those who normalize sBCMA demonstrated improved OS (P = 0·0078). Normalizing patients also experienced a markedly improved overall response rate (P < 0·0001). Moreover, all patients who achieved complete remission (CR) showed normalization of sBCMA, and time to normalization (median 0·9 months) was faster than time to CR (5·0 months; P = 0·0036) for these patients. These results suggest that normalization of sBCMA may be an accurate predictor of OS for MM patients during treatment and predict for a higher likelihood of response.
A rationale for targeting the P2X7 receptor in Coronavirus disease 19
Authors: Di Virgilio Francesco , Tang Yong , Sarti Alba Clara , Rossato Marco
Published: May 2020

Severe pneumonia which shares several of the features of acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid‐19) for which there is no effective treatment, so far. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung oedema, inflammatory cell infiltration, and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid‐19‐associated severe pneumonia.

Linked Articles

This article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
Dams and protected areas: Quantifying the spatial and temporal extent of global dam construction within protected areas
Authors: Thieme Michele L. , Khrystenko Dmytro , Qin Siyu , Golden Kroner Rachel E. , Lehner Bernhard , Pack Shalynn , Tockner Klement , Zarfl Christiane , Shahbol Natalie , Mascia Michael B.
Published: May 2020

Protected areas (PAs) are an essential tool for freshwater biodiversity conservation. Given past and expected future global increases in dams and impacts of dams on freshwater ecosystems, we document the number of dams existing or planned within PAs, their history, and the extent of PA downgrading, downsizing, and degazettement (PADDD) proximally caused by dams. Globally, at least 1,249 large dams are located within PAs; two‐thirds (907) were built before PA establishment. Additionally, 14% of planned geolocated hydropower dams (509 dams) are located within PAs. PADDD events have also legalized dam construction within existing PAs. Environmental safeguards should preclude development of dams within or adjacent to PAs and prioritize dams within PAs for possible removal and restoration.
Impacts of a trophy hunting ban on private land conservation in South African biodiversity hotspots
Authors: Parker Kim , De Vos Alta , Clements Hayley S. , Biggs Duan , Biggs Reinette
Published: May 2020

Private land conservation areas (PLCAs) have become critical for achieving global conservation goals, but we lack understanding of how and when these areas respond to global pressures and opportunities. In southern Africa, where many PLCAs rely on trophy hunting as an income‐generating strategy, a potential ban on trophy hunting locally or abroad holds unknown consequences for the future conservation of these lands. In this study, we investigate the consequences of a potential trophy hunting ban in PLCAs in two biodiversity hotspots in South Africa's Eastern and Western Cape provinces. We used semistructured interviews with PLCA managers and owners to elicit perceived impacts of an internationally imposed trophy hunting ban on conservation activities in PLCAs, and to probe alternative viable land uses. The majority of interviewees believed that both the economic viability of their PLCA and biodiversity would be lost following a hunting ban. Owners would primarily consider transitioning to ecotourism or livestock farming, but these options were constrained by the social‐ecological context of their PLCA (e.g., competition with other PLCAs, ecological viability of farming). Our results suggest that a trophy hunting ban may have many unintended consequences for biodiversity conservation, national economies, and the livelihoods of PLCA owners and employees. Along with similar social‐ecological studies in other areas and contexts, our work can inform policy decisions around global trophy hunting regulation.
Time to Step Up: A Call to Action For the Clinical and Quantitative Pharmacology Community to Accelerate Therapeutics for COVID‐19
Authors: Hartman Dan , Kern Steven , Brown Fran , Minton Suzanne K. , Rayner Craig R.
Published: May 2020

The global response to finding therapeutics for coronavirus disease 2019 (COVID‐19) is chaotic even if well intentioned. There is an opportunity, but more importantly, an obligation for the global clinical and quantitative pharmacology community to come together and use our state‐of‐the‐art tools and expertise to help society accelerate therapeutics to fight COVID‐19. This brief commentary is a call to action and highlights how the global pharmacology community should contribute to the COVID‐19 pandemic and prepare for future pandemics.