bluuebunny/crossref_metadata_2025 huggingface dataset:
Building employability capabilities in data science students: An interdisciplinary, industry‐focused approach
Authors: Ferns Sonia , Phatak Aloke , Benson Susan , Kumagai Nina
Published: June 2021

In the contemporary workplace, data scientists who are capable of interdisciplinary collaboration are in high demand. Universities need to provide data science students with a plethora of learning opportunities that involve collaboration in interdisciplinary contexts and engagement with industry partners. Curtin University and Lab Tests Online Australasia (LTOAU) collaborated to provide an interdisciplinary, industry‐focused learning experience for data science students. Upon completing the project, students reported improved understanding of the range of applications for data science skills. The experience delivered opportunities for greater self‐awareness and highlighted the importance of teamwork, decision‐making and leadership skills. This chapter presents Interdisciplinary Project‐based Work‐Integrated Learning (IPjWIL), an educational approach that equips data science students with the necessary skills to navigate the future world of work. The results of the pilot project described demonstrate how interdisciplinary, industry‐focused learning experiences enhance the capabilities of data science students, thereby augmenting employability.
Comparing four contemporary statistical software tools for introductory data science and statistics in the social sciences
Authors: Abbasnasab Sardareh Sedigheh , Brown Gavin T. L. , Denny Paul
Published: June 2021

Research students in social science disciplines frequently struggle to master statistical analysis. A contributing factor may be the statistical software that is used, as the design of such software may not address the needs of non‐statisticians or non‐computer programming students. Hence, decisions about which statistical software tools are most suitable for such end‐users need to be made at the introductory level. This paper first identifies key human‐computer interaction (HCI) factors that may directly influence students' statistical analysis performance. Factors include technical properties such as user interface design, statistical features available, visualization, data handling, preparation, and manipulation, and usage properties such as speed/number of steps, ease of command/use, and efficiency. Four popular software systems (ie, SPSS, R within RStudio Desktop, R Commander & jamovi) were evaluated. Findings suggest that HCI usage factors from an interaction perspective are likely to be especially important for students gaining an introductory knowledge of statistics.
Migrants’ involvement in health policy, service development and research in the WHO European Region: A narrative review of policy and practice
Authors: MacFarlane Anne , Ogoro Mamobo , de Freitas Claudia , Niranjan Vikram , Severoni Santino , Waagensen Elisabeth
Published: June 2021

OBJECTIVES

The involvement of individuals and communities in health decision‐making is enshrined in WHO policies. However, migrant groups are under‐represented in health decision‐making processes. Our aim was to explore migrants’ involvement in health policy, service development and research in the WHO European Region to identify levers for inclusive and meaningful practice.

METHODS

We conducted a narrative review of grey literature and peer‐reviewed research on migrants’ involvement in health decision‐making across the 53 countries in WHO Europe. We searched for articles published in English between 2010 and the present in two electronic databases (PubMed, Scopus), IOM MIPEX Health Strand country reports, the EU SOPHIE project and using a Google advanced search. Findings were analysed descriptively and using Normalisation Process Theory to investigate levers and barriers to implementation of policy into practice.

RESULTS

Of 1,444 articles retrieved, 79 met the inclusion criteria. We identified 20 policies promoting migrants’ involvement, but national‐level policies were present in only two countries. We identified 59 examples of migrants’ involvement in practice from half of the WHO Europe countries (n = 27). Our Normalisation Process Theory (NPT) analysis of 14 peer‐reviewed empirical papers found that participatory research approaches are a lever to putting policy into practice in a meaningful way.

CONCLUSIONS

Migrants’ involvement in health decision‐making requires explicit national policies that are implemented evenly across policymaking, service provider and research activities in all countries in the WHO European Region. Participatory approaches to involvement activities are encouraged because they are a lever to perceived barriers to migrants’ involvement.
Exploring optical coherence tomography imaging depth to differentiate tissues at surgical margins
Authors: Lages Maisa , Selmic Laura E.
Published: June 2021

Optical coherence tomography (OCT) is an imaging modality that provides real‐time visualization of tissue microstructure. The goals of this study were to assess OCT image tissue depths (TD) with image processing, and other objective characteristics of tissue types at surgical margins in canine soft tissue sarcoma (STS). In this study, a single observer reviewed 248 images of four tissue types (sarcoma, skeletal muscle, adipose and fascia) collected from 24 dogs with STS. The observer evaluated for tissue characteristics and measured TDs utilizing ImageJ software. Images were evaluated in normal, Threshold and Binary conditions. Measurements were repeated 1 week later to evaluate for intra‐observer variability. In all three image processing conditions, the order of TD from greatest to least light penetration was adipose, skeletal muscle, fascia and sarcoma tissue. Neovascularization was observed in 53.2% sarcoma, and lines of fascia surrounding muscle bundles was present in 93.5% of skeletal muscle images. These observed differences between tissue types in OCT images can be utilized to improve observer evaluation, aid in development of algorithms, and improve the accuracy of surgical margin assessment.
Global prevalence of Mycobacterium bovis infections among human tuberculosis cases: Systematic review and meta‐analysis
Authors: Taye Hawult , Alemu Kassahun , Mihret Adane , Wood James L. N. , Shkedy Ziv , Berg Stefan , Aseffa Abraham
Published: June 2021

Tuberculosis (TB) is a chronic communicable bacterial disease caused by Mycobacterium tuberculosis complex (MTBC) species. M. tuberculosis is the main causative agent of human TB, and cattle are the primary host of Mycobacterium bovis; due to close interaction between cattle and humans, M. bovis poses a zoonotic risk. This review summarizes and estimates the prevalence of M. bovis infection among human cases. Studies reporting TB prevalence data that were published in English during 10 years from 20 April 2009 to 17 April 2019 were identified through search of PubMed and other sources. Quality of studies and risk of bias were assessed using standard tools for prevalence study reports. Characteristics of included studies and their main findings were summarized in tables and discussed with narrative syntheses. Meta‐analysis was performed on 19 included studies, with a total of 7,185 MTBC isolates identified; 702 (9.7%) of them were characterized as of subspecies M. bovis, but there was a large prevalence difference between the studies, ranging from 0.4% to 76.7%. The genotyping‐based studies reported significantly lower prevalence of zoonotic TB than did the studies based on older techniques. The overall pooled prevalence of M. bovis aggregated from all included studies was 12.1% of the total MTBC isolates, while the corresponding pooled figure from the 14 genotyping‐based studies was only 1.4%. Generally, human M. bovis cases reported from different countries of the world suggest that the impact of zoonotic TB is still important in all regions. However, it was difficult to understand the true picture of the disease prevalence because of methodological differences. Future investigations on zoonotic TB should carefully consider these differences when evaluating prevalence results.
Model Testing as Applied to Strength of Materials
Authors: Peterson R. E.
Published: June 2021

This paper is primarily concerned with the effect of size on the ordinary strength properties of materials. The use of models in stress analysis is described briefly. The effect of size in tension, fatigue, and impact tests is considered in detail. Possible explanations for departure from the law of similarity are stated.
Factors Affecting Choice of Working Stresses for High-Temperature Service
Authors: McVetty P. G.
Published: June 2021

This paper discusses the various methods which have been proposed to determine safe working stresses for high-temperature service. The question of the stability of alloys during the test and in subsequent service is considered, with particular emphasis upon probable changes in creep characteristics during long exposure to stress and temperature. It is shown that published data in general do not admit of extrapolation, and that attempts to estimate total creep in service from such data are not usually satisfactory. The author stresses the need for more fundamental study of the laws governing creep rather than creep tests of many different materials.
Theories of Strength
Authors: Nadai A.
Published: June 2021

The conditions under which yielding starts at lower temperatures in metallic and also in other materials are discussed. Recent tests, particularly those made in England, Germany, Switzerland, and the United States, are compared and the results of a number of new ones concerning the conditions of yielding of steel are reported.

More detailed reference to these tests is made, and conclusions as to the best expressions available at present are drawn from them and utilized in rules for computing working stresses in practical cases. In conclusion, certain suggestions are made as to the conditions of ordinary rupture in a static test.
The New Theory of Plasticity, Strain Hardening, and Creep, and the Testing of the Inelastic Behavior of Metals
Authors: Hencky H.
Published: June 2021

The knowledge of the inelastic behavior of metals has experienced considerable growth in the last few years. To draw all the advantages possible from the experiments, frequently very difficult, an effort has been made to bring the entire development under some dominating physical ideas. These ideas are in fact very old, and deal mainly with the proper conception of the hidden elastic energy that is responsible for the statical component of the strain hardening. The analytical treatment of the inelastic behavior gives promise of being valuable not only in the testing of materials, but even for the designer of machines used in the forming of metals.
Development and Verification of an Integrated Seawater Desalination and Renewable Energy System Model
Authors: Bani Salim Muath , Zhang Xuewei
Published: June 2021

This work investigates the modeling and verification of seawater reverse osmosis powered by renewable energy resources (SWRO-RES). The model includes one stage of RO membranes, high pressure (HP) pump, energy recovery devices (ERD), Wind turbines (WT), photovoltaic panels (PV), and electrical grid as a back-up for the cases when there is weak penetration of the RES. Antibugging and tracing for the computer model were used as part of the code verification to discover all coding errors and check whether the computer model conforms to the SWRO specifications. After that, the calculations verifications process was performed using sensitivity analysis (SA) to evaluate whether the model response follows the anticipated direction and to check the model at some extreme conditions. Four SA cases were implemented to evaluate the SWRO-RES freshwater production, freshwater concentration, recovery rate, and specific energy consumption (SEC). Case 1 was the SA for different feed pressure values. In this case, it is important to find the pressure value that gives the lowest freshwater concentration. Case 2 was the SA for different feedwater temperature values. While case 3 was the SA for the feedwater concentration. In all these cases, the model shows a verified response and as anticipated. The last SA case was to study the effect of different numbers of WT and PV panels and evaluate the electrical grid share considering one year of operation for the SWRO-RES plant.
Atomic precision imaging with an on-chip scanning tunneling microscope integrated into a commercial ultrahigh vacuum STM system
Authors: Alipour Afshin , Moheimani S. O. Reza , Owen James H. G. , Fuchs Ehud , Randall John N.
Published: June 2021

In this article, we replace the Z axis of the piezotube of a conventional Ultrahigh-Vacuum (UHV) Scanning Tunneling Microscope (STM) with a one-degree-of-freedom Microelectromechanical-System (MEMS) nanopositioner. As a result, a hybrid system is realized in which motions in the XY plane are carried out by the piezotube, while the MEMS device performs the Z-axis positioning with a smaller footprint and higher sensitivity. With the proposed system and a feedback loop, STM imaging is conducted on an H-passivated Si (100)-2×1 sample in a UHV condition, demonstrating that this on-chip STM is conducive to atomic precision scanning tunneling microscopy.
Associations Between Household Socioeconomic Status, Car Ownership, Physical Activity, and Cardiorespiratory Fitness in South African Primary Schoolchildren Living in Marginalized Communities
Authors: Gerber Markus , Lang Christin , Beckmann Johanna , Degen Jan , du Randt Rosa , Gall Stefanie , Long Kurt Z. , Müller Ivan , Nienaber Madeleine , Steinmann Peter , Pühse Uwe , Utzinger Jürg , Nqweniso Siphesihle , Walter Cheryl
Published: June 2021

Background: Little is known whether physical activity (PA)-promoting environments are equally accessible to children with divergent socioeconomic status (SES) in low-/middle-income countries. The authors, therefore, examined whether South African children from poorer versus wealthier families living in marginalized communities differed in moderate to vigorous PA and cardiorespiratory fitness. We also tested associations between family car ownership and PA/cardiorespiratory fitness. Methods: Parents/guardians of 908 children (49% girls, mean age = 8.3 [1.4] y) completed a survey on household SES. PA was assessed via 7-day accelerometry, parental and child self-reports, and cardiorespiratory fitness with the 20-m shuttle run test. Results: Based on accelerometry, most children met current moderate to vigorous PA recommendations (≥60 min/d). About 73% of the children did not engage in structured physical education lessons. Whereas children of the lowest SES quintile accumulated higher levels of device-based moderate to vigorous PA, peers from the highest SES quintile engaged in more sedentary behaviors, but self-reported higher engagement in sports, dance, and moving games after school. Families’ car ownership was associated with higher parent/self-reported leisure-time PA. Conclusions: A deeper understanding is needed about why wealthier children are more sedentary, but simultaneously engage in more leisure-time PA. The fact that access to structural physical education is denied to most children is critical and needs to be addressed.
Biomechanics: 40 Years On
Authors: Hamill Joseph , Knutzen Kathleen M. , Derrick Timothy R.
Published: June 2021

In the last 40 years, biomechanics has progressed significantly as a subdiscipline within kinesiology. The development of national and international societies dedicated to biomechanics and the increase in the number of scientific biomechanics journals has led to a growth in the biomechanics community. In the last few decades, the research focus in biomechanics has broadened substantially. With this diversity of focus, there have been many novel developments in new technologies used in biomechanics. Biomechanics has become an integral subdiscipline that has interfaced with several other areas in kinesiology and has contributed significantly to enhancing the knowledge base in all areas. Much of the development of biomechanics has resulted from improvements in the technology used in movement research. Although it may be overreaching to say that biomechanics can solve many human movement problems, the technology has allowed researchers to at least answer more comprehensive questions and answer them in greater depth.
How green can Amazon hydropower be? Net carbon emission from the largest hydropower plant in Amazonia
Authors: Bertassoli Dailson J. , Sawakuchi Henrique O. , de Araújo Kleiton R. , de Camargo Marcelo G. P. , Alem Victor A. T. , Pereira Tatiana S. , Krusche Alex V. , Bastviken David , Richey Jeffrey E. , Sawakuchi André O.
Published: June 2021

GHG emissions from the Belo Monte reservoirs in Brazilian Amazon are up to three times higher than preimpoundment fluxes.
Strong links between Saharan dust fluxes, monsoon strength, and North Atlantic climate during the last 5000 years
Authors: Cruz Juncal A. , McDermott Frank , Turrero María J. , Edwards R. Lawrence , Martín-Chivelet Javier
Published: June 2021

Stalagmite strontium isotopes reveal large rises in Saharan dust over Europe preluding major climate cold events.
Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis
Authors: Kwon Hyuk-Kwon , Lee Inkyu , Yu Kristin E. , Cahill Sean V. , Alder Kareme D. , Lee Saelim , Dussik Christopher M. , Back JungHo , Choi Jeongjoon , Song Lee , Kyriakides Themis R. , Lee Francis Y.
Published: June 2021

Combined targeting of both intra-articular infection and inflammation achieves greater chondroprotection in septic arthritis.
Glucagon regulates the stability of REV-ERBα to modulate hepatic glucose production in a model of lung cancer–associated cachexia
Authors: Verlande Amandine , Chun Sung Kook , Goodson Maggie O. , Fortin Bridget M. , Bae Hosung , Jang Cholsoon , Masri Selma
Published: June 2021

Glucagon signaling governs REV-ERBα stability to modulate hepatic glucose production in a model of lung cancer cachexia.
Sea level and deep-sea temperature reconstructions suggest quasi-stable states and critical transitions over the past 40 million years
Authors: Rohling Eelco J. , Yu Jimin , Heslop David , Foster Gavin L. , Opdyke Bradley , Roberts Andrew P.
Published: June 2021

New reconstructions suggest quasi-stable states and critical transitions in climate over the past 40 million years.
Engineered yeast tolerance enables efficient production from toxified lignocellulosic feedstocks
Authors: Lam Felix H. , Turanlı-Yıldız Burcu , Liu Dany , Resch Michael G. , Fink Gerald R. , Stephanopoulos Gregory
Published: June 2021

Rationally engineered tolerance enables broadly efficient lignocellulosic fermentation of diverse feedstocks and bioproducts.
Nuclear dynamics of singlet exciton fission in pentacene single crystals
Authors: Seiler Hélène , Krynski Marcin , Zahn Daniela , Hammer Sebastian , Windsor Yoav William , Vasileiadis Thomas , Pflaum Jens , Ernstorfer Ralph , Rossi Mariana , Schwoerer Heinrich
Published: June 2021

Coherent and incoherent long-range atomic motions accompany singlet exciton fission in pentacene.
Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of
C. elegans
Authors: Calculli Giuseppe , Lee Hyun Ju , Shen Koning , Pham Uyen , Herholz Marija , Trifunovic Aleksandra , Dillin Andrew , Vilchez David
Published: June 2021

Germline proteostasis coordinates mitochondrial networks and aggregation of disease-related proteins across the organism.
Liquid film–induced critical heat flux enhancement on structured surfaces
Authors: Li Jiaqi , Kang Daniel , Fazle Rabbi Kazi , Fu Wuchen , Yan Xiao , Fang Xiaolong , Fan Liwu , Miljkovic Nenad
Published: June 2021

A liquid film with two distinct contact lines underneath bubbles during boiling on structured surfaces has been discovered.
Multiplexed, quantitative serological profiling of COVID-19 from blood by a point-of-care test
Authors: Heggestad Jacob T. , Kinnamon David S. , Olson Lyra B. , Liu Jason , Kelly Garrett , Wall Simone A. , Oshabaheebwa Solomon , Quinn Zachary , Fontes Cassio M. , Joh Daniel Y. , Hucknall Angus M. , Pieper Carl , Anderson Jack G. , Naqvi Ibtehaj A. , Chen Lingye , Que Loretta G. , Oguin Thomas , Nair Smita K. , Sullenger Bruce A. , Woods Christopher W. , Burke Thomas W. , Sempowski Gregory D. , Kraft Bryan D. , Chilkoti Ashutosh
Published: June 2021

A point-of-care, microfluidic platform detects antibodies against three SARS-CoV-2 antigens from blood in less than an hour.
Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging
Authors: Kerepesi Csaba , Zhang Bohan , Lee Sang-Goo , Trapp Alexandre , Gladyshev Vadim N.
Published: June 2021

Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging.
Improved simulation of 19th- and 20th-century North Atlantic hurricane frequency after correcting historical sea surface temperatures
Authors: Chan Duo , Vecchi Gabriel A. , Yang Wenchang , Huybers Peter
Published: June 2021

Correcting historical sea surface temperature improves the simulation of 19th- and 20th-century North Atlantic hurricane activity.
Enhancing the phase stability of ceramics under radiation via multilayer engineering
Authors: Zhang Hongliang , Xi Jianqi , Su Ranran , Hu Xuanxin , Kim Jun Young , Wei Shuguang , Zhang Chenyu , Shi Liqun , Szlufarska Izabela
Published: June 2021

This study provides a strategy to improve the phase stability of ceramic material under radiation through interface engineering.
Electronics with shape actuation for minimally invasive spinal cord stimulation
Authors: Woodington Ben J. , Curto Vincenzo F. , Yu Yi-Lin , Martínez-Domínguez Héctor , Coles Lawrence , Malliaras George G. , Proctor Christopher M. , Barone Damiano G.
Published: June 2021

Electronics that change shape inside the body enable keyhole surgery of spinal implants that can treat severe pain.
Structure of the mycobacterial ESX-5 type VII secretion system pore complex
Authors: Beckham Katherine S. H. , Ritter Christina , Chojnowski Grzegorz , Ziemianowicz Daniel S. , Mullapudi Edukondalu , Rettel Mandy , Savitski Mikhail M. , Mortensen Simon A. , Kosinski Jan , Wilmanns Matthias
Published: June 2021

The structure of the mycobacterial ESX-5 secretion system reveals a central transmembrane pore.
Opto-refrigerative tweezers
Authors: Li Jingang , Chen Zhihan , Liu Yaoran , Kollipara Pavana Siddhartha , Feng Yichao , Zhang Zhenglong , Zheng Yuebing
Published: June 2021

Localized laser cooling provides a new way to trap and manipulate small objects.
Delta variant triggers new phase in the pandemic
Authors: Kupferschmidt Kai , Wadman Meredith
Published: June 2021

Scientists are probing why a fresh set of viral mutations is taking the world by storm.
Supplemental Material: The products of primary magma fragmentation finally revealed by pumice agglomerates
Authors: Giachetti Thomas , al. et
Published: June 2021

Additional information on (1) the four eruptions studied and sample collection, (2) lapilli selection, (3) measurements of volume and porosity, (4) analysis by X-Ray computed tomography and scanning electron microscopy, and (5) calculation of protopyroclasts size distributions.
Effectiveness of workplace active rest programme on low back pain in office workers: a stepped-wedge cluster randomised controlled trial
Authors: Tsuboi Yamato , Oka Tomohiro , Nakatsuka Kiyomasa , Isa Tsunenori , Ono Rei
Published: June 2021

Objective

This study aimed to investigate the effectiveness of workplace active rest programme (WARP) on chronic low back pain (LBP) among office workers.

Design

A closed cohort, stepped-wedge cluster randomised trial was conducted. The total duration of the study was 16 weeks (4 weeks for each step). Sequence allocation was randomised, but no one was blinded.

Setting

This study was conducted in three offices in a Japanese electronics company. One office was for the administrative department, the others are for the engineering department.

Participants

We recruited 29 office workers with LBP greater than 3 months. LBP due to specific injury or disease was excluded. The median age was 38 years, and 26 (90%) were male. All participants completed the study.

Interventions

In the intervention phase, participants performed WARP comprising frequent stand-up and individualised brief exercise/physical activity during work. Physical therapists held an LBP workshop and developed tailor-made programmes before introducing WARP. We instructed participants to perform WARP at five timings during work. Control phase was set before the intervention and participants stayed as usual.

Primary and secondary outcome measures

The primary outcome was pain intensity of LBP assessed using the Brief Pain Inventory. The secondary outcomes were work productivity loss measured using the Work Limitations Questionnaire, LBP disability assessed using the Roland-Morris Disability Questionnaire, psychosocial subscale assessed using the STarT Back Screening Tool and physical activity measured using triaxial accelerometers. These outcomes were collected at baseline and at 4-month follow-up evaluation.

Results

In the intention-to-treat analysis, WARP did not show any significant effects on pain intensity (β, 0.01; 95% CI −0.50 to 0.52) and on the secondary outcomes. The median adherence to WARP was 28.6% (IQR, 16.8–41.1), which was equal to 1.43 times per day. No adverse effect was observed.

Conclusions

The present study was unable to confirm the effectiveness of active rest in improving LBP. Hence, further study needs to investigate its effectiveness.

Trial registration number

UMIN000033210.
How to increase the attractiveness of undergraduate rural clerkships? A cross-sectional study among medical students at two German medical schools
Authors: Herget Sabine , Nafziger Melanie , Sauer Stephanie , Bleckwenn Markus , Frese Thomas , Deutsch Tobias
Published: June 2021

Objectives

While literature provides substantial evidence that undergraduate rural clerkships may contribute to attract medical students to rural careers, so far little is known about how to convince medical students to choose rural teaching sites for their clerkships, which is usually optional. Thus, this study aimed to investigate students’ preferences and perceptions regarding different rural teaching and clerkship formats, important side conditions and suitable communication strategies to promote rural clerkships.

Design

Cross-sectional study based on a quantitative survey among medical students in advanced study years.

Setting

Two German medical schools (Leipzig and Halle-Wittenberg).

Participants

Medical students in third to fifth year (of six).

Results

Response rate was 87.1% with n=909 analysable questionnaires. Participants’ mean age was 25.0 years and 65.2% were women. For 97.9% of the students completing some kind of rural clerkship was imaginable, for 90.8% even participation in a rural clerkship of 4 weeks and longer. Nearly half of the students (48.0%) specified that a rural clerkship 4 weeks and longer was ‘absolutely imaginable’. Younger age, having grown up in a rural or small-town region, being able to imagine future working in a small-town or rural area, and general practice as favoured, or at least conceivable career option were independently associated with a higher willingness to complete longer rural clerkships. Financial and organisational issues including remuneration of the clerkship, cost absorption for travelling and accommodation, and accessibility by public transport were the most important side conditions to increase the attractiveness of rural clerkships. Experience reports by fellow students, social media and informational events were stated to be the most suitable ways to advertise rural teaching offers.

Conclusions

The majority of the students are open-minded regarding even longer rural clerkships. This study adds new insights into measures that should be taken to convince them to actually chose this option.
Factors associated with incomplete immunisation in children aged 12–23 months at subnational level, Nigeria: a cross-sectional study
Authors: Eze Paul , Agu Ujunwa Justina , Aniebo Chioma Lynda , Agu Sergius Alex , Lawani Lucky Osaheni , Acharya Yubraj
Published: June 2021

Objectives

National immunisation coverage rate masks subnational immunisation coverage gaps at the state and local district levels. The objective of the current study was to determine the sociodemographic factors associated with incomplete immunisation in children at a sub-national level.

Design

Cross-sectional study using the WHO sampling method (2018 Reference Manual).

Setting

Fifty randomly selected clusters (wards) in four districts (two urban and two rural) in Enugu state, Nigeria.

Participants

1254 mothers of children aged 12–23 months in July 2020.

Primary and secondary outcome measures

Fully immunised children and not fully immunised children.

Results

Full immunisation coverage (FIC) rate in Enugu state was 78.9% (95% CI 76.5% to 81.1%). However, stark difference exists in FIC rate in urban versus rural districts. Only 55.5% of children in rural communities are fully immunised compared with 94.5% in urban communities. Significant factors associated with incomplete immunisation are: children of single mothers (aOR=5.74, 95% CI 1.45 to 22.76), children delivered without skilled birth attendant present (aOR=1.93, 95% CI 1.24 to 2.99), children of mothers who did not receive postnatal care (aOR=6.53, 95% CI 4.17 to 10.22), children of mothers with poor knowledge of routine immunisation (aOR=1.76, 95% CI 1.09 to 2.87), dwelling in rural district (aOR=7.49, 95% CI 4.84 to 11.59), low-income families (aOR=1.56, 95% CI 1.17 to 2.81) and living further than 30 min from the nearest vaccination facility (aOR=2.15, 95% CI 1.31 to 3.52).

Conclusions

Although the proportion of fully immunised children in Enugu state is low, it is significantly lower in rural districts. Study findings suggest the need for innovative solutions to improve geographical accessibility and reinforce the importance of reporting vaccination coverage at local district level to identify districts for more targeted interventions.
Mortality trends and access to care for cardiovascular diseases in Agincourt, rural South Africa: a mixed-methods analysis of verbal autopsy data
Authors: Newberry Le Vay Jessica , Fraser Andrew , Byass Peter , Tollman Stephen , Kahn Kathleen , D’Ambruoso Lucia , Davies Justine I
Published: June 2021

Objectives

Cardiovascular diseases are the second leading cause of mortality behind HIV/AIDS in South Africa. This study investigates cardiovascular disease mortality trends in rural South Africa over 20+ years and the associated barriers to accessing care, using verbal autopsy data.

Design

A mixed-methods approach was used, combining descriptive analysis of mortality rates over time, by condition, sex and age group, quantitative analysis of circumstances of mortality (CoM) indicators and free text narratives of the final illness, and qualitative analysis of free texts.

Setting

This study was done using verbal autopsy data from the Health and Socio-Demographic Surveillance System site in Agincourt, rural South Africa.

Participants

Deaths attributable to cardiovascular diseases (acute cardiac disease, stroke, renal failure and other unspecified cardiac disease) from 1993 to 2015 were extracted from verbal autopsy data.

Results

Between 1993 and 2015, of 15 305 registered deaths over 1 851 449 person-years of follow-up, 1434 (9.4%) were attributable to cardiovascular disease, corresponding to a crude mortality rate of 0.77 per 1000 person-years. Cardiovascular disease mortality rate increased from 0.34 to 1.12 between 1993 and 2015. Stroke was the dominant cause of death, responsible for 41.0% (588/1434) of all cardiovascular deaths across all years. Cardiovascular disease mortality rate was significantly higher in women and increased with age. The main delays in access to care during the final illness were in seeking and receiving care. Qualitative free-text analysis highlighted delays not captured in the CoM, principally communication between the clinician and patient or family. Half of cases initially sought care outside a hospital setting (50.9%, 199/391).

Conclusions

The temporal increase in deaths due to cardiovascular disease highlights the need for greater prevention and management strategies for these conditions, particularly for the women. Strategies to improve seeking and receiving care during the final illness are needed.
Effectiveness of combined vaginal progesterone and cervical cerclage in preventing preterm birth: a systematic review and meta-analysis protocol
Authors: Diacci Rosanna C , Issah Ashad , Williams Kimberley P , McAuliffe Liam , Aubin Anne-Marie , McAuliffe Jack E , Phung Jason , Wang Carol A , Pennell Craig E
Published: June 2021

Introduction

Preterm birth (PTB) is the leading cause of death in children under 5 years. Preventive therapies targeted towards women with risk factors such as a prior PTB or a short cervix reduce the rate of PTB. Cervical cerclage, vaginal progesterone and a combination of the two have been used with no consensus as to whether combined treatment is more effective than any single treatment alone. The objective of this review is to determine the efficacy of combined treatment compared with cerclage alone and combined treatment compared with progesterone alone.

Methods and analysis

Studies will be sourced from the electronic databases Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Scopus, CINAHL (EBSCOhost) and Cochrane Library (Wiley) and reference lists. We will not exclude any papers due to publication date. Randomised control trials (RCTs), non-RCTs and cohort studies assessing single therapy (either progesterone or cerclage) versus combined therapy in women with a singleton pregnancy will be included. Two independent reviewers will conduct study screening (at abstract and full-text level), data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. Random or fixed effects models will be used depending on data heterogeneity and data will be presented as risk ratio for dichotomous data or mean difference for continuous data with a CI of 95% used for all outcomes.

Ethics and dissemination

Not applicable due to nature of the study type.

PROSPERO registration number

CRD42020195975.
Country of birth, educational level and other predictors of seeking care due to decreased fetal movements: an observational study in Sweden using data from a cluster-randomised controlled trial
Authors: Radestad Ingela , Pettersson Karin , Lindgren Helena , Skokic Viktor , Akselsson Anna
Published: June 2021

Objectives

To identify predictors of seeking care for decreased fetal movements and assess whether care-seeking behaviour is influenced by Mindfetalness.

Design

Observational study with data from a cluster-randomised controlled trial.

Setting

67 maternity clinics and 6 obstetrical clinics in Sweden.

Participants

All pregnant women with a singleton pregnancy who contacted the obstetrical clinic due to decreased fetal movements from 32 weeks’ gestation of 39 865 women.

Methods

Data were collected from a cluster-randomised controlled trial where maternity clinics were randomised to Mindfetalness or routine care. Mindfetalness is a self-assessment method for women to use daily to become familiar with the unborn baby’s fetal movement pattern.

Outcome measures

Predictors for contacting healthcare due to decreased fetal movements.

Results

Overall, 5.2% (n=2059) of women contacted healthcare due to decreased fetal movements, among which 1287 women (62.5%) were registered at a maternity clinic randomised to Mindfetalness and 772 women (37.5%) were randomised to routine care. Predictors for contacting healthcare due to decreased fetal movements were age, country of birth, educational level, parity, prolonged pregnancy and previous psychiatric care (p<0.001). The main differences were seen among women born in Africa as compared with Swedish-born women (2% vs 6%, relative risk (RR) 0.34, 95% CI 0.25 to 0.44) and among women with low educational level compared with women with university-level education (2% vs 5.4%, RR 0.36, 95% CI 0.19 to 0.62). Introducing Mindfetalness in maternity care increased the number of women seeking care due to decreased fetal movements overall.

Conclusion

Women with country of birth outside Sweden and low educational level sought care for decreased fetal movements to a lesser extent compared with women born in Sweden and those with university degrees. Future research could explore whether pregnancy outcomes can be improved by motivating women in these groups to contact healthcare if they feel a decreased strength or frequency of fetal movements.

Trial registration number

NCT02865759.
Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer
Authors: Zhai Tianhang , Wang Chao , Xu Yifeng , Huang Weifeng , Yuan Zhijun , Wang Tao , Dai Shuang , Peng Shaogang , Pang Tuling , Jiang Wenchao , Huang Yuhua , Zou Yuefeng , Xu Yingda , Sun Joanne , Gong Xinjiang , Zhang Jinping , Tsun Andy , Li Bin , Miao Xiaoniu
Published: June 2021

Background

The discovery of checkpoint inhibitors towards cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has been revolutionary for the treatment of cancers. These therapies have only offered an average of 20%–30% response rates across the tumor spectrum and the combination of agonists towards the tumor-necrosis superfamily members, such as 4-1BB and CD40, has shown potent efficacy in preclinical studies; however, these agonists have exhibited high degrees of toxicity with limited efficacy in human trials. In this study, we have generated a single-domain antibody towards a unique epitope of 4-1BB that limits its potential on-target toxicity while maintaining sufficient potency. This 4-1BB binder is ideal for use in the engineering of multispecific antibodies to localize 4-1BB activation within the tumor microenvironment, as shown here by a anti-PD-L1/4-1BB bispecific candidate (PM1003).

Methods

To determine the functional activity of the 4-1BB- and PD-L1-binding elements of PM1003, in vitro luciferase reporter and primary cell assays were used to test the potency of programmed cell death 1 ligand 1 (PD-L1) blockade and PD-L1-mediated 4-1BB activation via cross-bridging. X-ray crystallography was conducted to resolve the binding epitopes of the respective binding arms, and accurate binding kinetics were determined using standard affinity measurement techniques. Human 4-1BB and/or PD-L1 knock-in mice were used in cancer models for testing the in vivo antitumor efficacy of PM1003, and safety was evaluated further.

Results

PM1003 shows potent activation of 4-1BB and blockade of PD-L1 in cell-based assays. 4-1BB activation was exerted through the bridging of PD-L1 on target cells and 4-1BB on effector cells. No PD-L1-independent activation of 4-1BB was observed. Through X-ray crystallography, a unique binding epitope in the cysteine-rich domain 4 (CRD4) region was resolved that provides high potency and potentially low on-target toxicity as determined by primary immune cell assays and toxicity evaluation in vivo.

Conclusions

A unique single-domain antibody was discovered that binds to the CRD4 domain of 4-1BB. When incorporated into a 4-1BB/PD-L1 bispecific (PM1003), we have shown the potent inhibition of PD-L1 activity with 4-1BB agonism upon cross-bridging with PD-L1 in vitro. Antitumor activity with minimal toxicity was found in vivo. Thus, PM1003 is a uniquely differentiating and next generation therapeutic agent for cancer therapy.
Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy
Authors: Reimann Hannah , Nguyen Andrew , Sanborn J Zachary , Vaske Charles J , Benz Stephen C , Niazi Kayvan , Rabizadeh Shahrooz , Spilman Patricia , Mackensen Andreas , Ruebner Matthias , Hein Alexander , Beckmann Matthias W , van der Meijden Edith D , Bausenwein Judith , Kretschmann Sascha , Griffioen Marieke , Schlom Jeffrey , Gulley James L , Lee Karin L , Hamilton Duane H , Soon-Shiong Patrick , Fasching Peter A , Kremer Anita N.
Published: June 2021

Background

Therapeutic regimens designed to augment the immunological response of a patient with breast cancer (BC) to tumor tissue are critically informed by tumor mutational burden and the antigenicity of expressed neoepitopes. Herein we describe a neoepitope and cognate neoepitope-reactive T-cell identification and validation program that supports the development of next-generation immunotherapies.

Methods

Using GPS Cancer, NantOmics research, and The Cancer Genome Atlas databases, we developed a novel bioinformatic-based approach which assesses mutational load, neoepitope expression, human leukocyte antigen (HLA)-binding prediction, and in vitro confirmation of T-cell recognition to preferentially identify targetable neoepitopes. This program was validated by application to a BC cell line and confirmed using tumor biopsies from two patients with BC enrolled in the Tumor-Infiltrating Lymphocytes and Genomics (TILGen) study.

Results

The antigenicity and HLA-A2 restriction of the BC cell line predicted neoepitopes were determined by reactivity of T cells from HLA-A2-expressing healthy donors. For the TILGen subjects, tumor-infiltrating lymphocytes (TILs) recognized the predicted neoepitopes both as peptides and on retroviral expression in HLA-matched Epstein-Barr virus–lymphoblastoid cell line and BC cell line MCF-7 cells; PCR clonotyping revealed the presence of T cells in the periphery with T-cell receptors for the predicted neoepitopes. These high-avidity immune responses were polyclonal, mutation-specific and restricted to either HLA class I or II. Interestingly, we observed the persistence and expansion of polyclonal T-cell responses following neoadjuvant chemotherapy.

Conclusions

We demonstrate our neoepitope prediction program allows for the successful identification of neoepitopes targeted by TILs in patients with BC, providing a means to identify tumor-specific immunogenic targets for individualized treatment, including vaccines or adoptively transferred cellular therapies.
Incremental predictive value of left atrial strain and left atrial appendage function in rhythm outcome of non-valvular atrial fibrillation patients after catheter ablation
Authors: Ma Xin-Xin , Wang Aiqing , Lin Kaibin
Published: June 2021

Objective

The purpose of this study was to develop a non-invasive and convenient nomogram based on speckle tracking echocardiography, left atrial appendage function and clinical factors to predict the risk of atrial fibrillation (AF) recurrence after catheter ablation.

Methods

A total of 124 prospectively consecutive patients with AF treated with catheter ablation in our hospital was retrospectively analysis. Baseline echocardiographic parameters were measured by using transthoracic and transesophageal echocardiography before ablation. Multivariate analysis was performed for selecting predictors for a nomogram and internal validation and calibration were evaluated by the bootstep method.

Results

During the follow-up of 12±3 months, 41 patients (33.1%) occurred AF recurrence after catheter ablation, while 83 patients (66.9%) had maintained sinus rhythm. Four predictors (AF type, left atrial appendage emptying flow velocity, left Atrial maximal volumes index and global longitudinal strain) with the P<0.5 was selected into the nomogram according to multivariate findings. Internal validation by bootstrapping with 1000 resamples was determined C-index of the nomogram for prediction AF recurrence was 0.901, which showed optimal discrimination and calibration of the established nomogram.

Conclusions

Nomogram based on echocardiography and clinical characteristics had good predictive performance for the possibility of AF recurrence, which providing practical guidance for individualised management of patients with AF after catheter ablation.
Interhospital and interindividual variability in secondary prevention: a comparison of outpatients with a history of chronic coronary syndrome versus outpatients with a history of acute coronary syndrome (the iASPIRE Study)
Authors: Curneen James MG , Judge Conor , Traynor Bryan , Buckley Anthony , Saiva Lavanya , Murphy Laura , Murray Donal , Fleming Sean , Kearney Peter , Murphy Ross T , Aleong Godfrey , Kiernan Thomas J , O'Neill James , Moore David , Nicaodhabhui Bridog , Birrane John , Hall Patricia , Crowley James , Gibson Irene , Jennings Catriona S , Wood David , Kotseva Kornelia , McEvoy John William
Published: June 2021

Background

Studying variability in the care provided to secondary prevention coronary heart disease (CHD) outpatients can identify interventions to improve their outcomes.

Methods

We studied outpatients who had an index CHD event in the preceding 6–24 months. Eligible CHD events included acute coronary syndrome (ACS) and coronary revascularisation for stable chronic coronary syndrome (CCS). Site training was provided by a core team and data were collected using standardised methods.

Results

Between 2017 and 2019, we enrolled 721 outpatients at nine Irish study sites; 81% were men and mean age was 63.9 (SD ±8.9) years. The study examination occurred a median of 1.16 years after the index CHD event, which was ACS in 399 participants (55%) and stable-CCS in 322. On examination, 42.5% had blood pressure (BP) >140/90 mm Hg, 63.7% had low-density lipoprotein cholesterol (LDL-C) >1.8 mmol/L and 44.1% of known diabetics had an HbA1c >7%. There was marked variability in risk factor control, both by study site and, in particular, by index presentation type. For example, 82% of outpatients with prior-ACS had attended cardiac rehabilitation versus 59% outpatients with prior-CCS (p<0.001) and there were also large differences in control of traditional risk factors like LDL-C (p=0.002) and systolic BP (p<0.001) among outpatients with prior-ACS versus prior-CCS as the index presentation.

Conclusions

Despite international secondary prevention guidelines broadly recommending the same risk factor targets for all adults with CHD, we found marked differences in outpatient risk factor control and management on the basis of hospital location and index CHD presentation type (acute vs chronic). These findings highlight the need to reduce hospital-level and patient-level variability in preventive care to improve outcomes; a lesson that should inform CHD prevention programmes in Ireland and around the world.
Replication of Quasi-Experimental Population Studies: Motivation and Guidance
Authors: Cready William M.
Published: June 2021

Most quasi-experimental empirical analyses in accounting involve determining a set of sample selection criteria and then applying these criteria to obtain an exhaustive sample for analysis. By including all available observations, one might reasonably view such analyses as population studies. In this paper, I propose a structure and provide related interpretive guidance for conducting intentional, focused replications of population analyses defined by such sample selection criteria.