bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of α-mangostin on embryonic development and liver development in zebrafish
Authors: Pimtong Wittaya , Kitipaspallop Wannakarn , Chun Hang-Suk , Kim Woo-Keun
Published: September 2020

Background

Alpha-mangostin has potential as a chemopreventive agent but there is little information on its toxicological profile and developmental toxicity.

Objective

We evaluated the effects of α-mangostin on embryonic development and hepatogenesis in zebrafish.

Result

Exposure of embryos to 0.25–4 μM α-mangostin from 4–120 h post-fertilization (hpf) caused mortality of embryos with LC50 1.48 ± 0.29 μM. The compound also caused deformities, including head malformation, pericardial oedema, absence of swim bladder, yolk oedema, and bent tail. Exposure of zebrafish embryos to α-mangostin during early hepatogenesis (16–72 hpf) decreased the transcript expression levels of liver fatty acid-binding protein 10a (Fabp10a), but increased gene markers of inflammation, oxidative stress, and apoptosis. In Fabp10a:DsRed transgenic zebrafish, the intensity and the area of fluorescence in the liver of the treated group were decreased (non-significantly) relative to controls.

Conclusion

These effects were more marked during early hepatogenesis (16–72 hpf) than during post-hepatogenesis (72–120 hpf).
Assessing the potential of bioeconomy in Slovakia based on public perception of renewable materials in contrast to non-renewable materials
Authors: Navrátilová Lenka , Výbošťok Jozef , Dobšinská Zuzana , Šálka Jaroslav , Pichlerová Magdaléna , Pichler Viliam
Published: September 2020

There is a need for societal transformation towards bioeconomy, which promotes the replacement of non-renewable natural resources with renewable ones. Slovakia has considerable potential for bioeconomy development, yet this potential remains untapped. This article evaluates the public perception regarding the individual properties of renewable and non-renewable materials and their relation to the potential for bioeconomy development in Slovakia. It is found that Slovak consumers prefer natural renewable materials, regardless of other influencing factors, and realise the need for transformation towards a more sustainable economy.
Assumptions in ecosystem service assessments: Increasing transparency for conservation
Authors: Schröter Matthias , Crouzat Emilie , Hölting Lisanne , Massenberg Julian , Rode Julian , Hanisch Mario , Kabisch Nadja , Palliwoda Julia , Priess Jörg A. , Seppelt Ralf , Beckmann Michael
Published: September 2020

Conservation efforts are increasingly supported by ecosystem service assessments. These assessments depend on complex multi-disciplinary methods, and rely on a number of assumptions which reduce complexity. If assumptions are ambiguous or inadequate, misconceptions and misinterpretations may arise when interpreting results of assessments. An interdisciplinary understanding of assumptions in ecosystem service science is needed to provide consistent conservation recommendations. Here, we synthesise and elaborate on 12 prevalent types of assumptions in ecosystem service assessments. These comprise conceptual and ethical foundations of the ecosystem service concept, assumptions on data collection, indication, mapping, and modelling, on socio-economic valuation and value aggregation, as well as about using assessment results for decision-making. We recommend future assessments to increase transparency about assumptions, and to test and validate them and their potential consequences on assessment reliability. This will support the taking up of assessment results in conservation science, policy and practice.
A conceptual model of the social–ecological system of nature-based solutions in urban environments
Authors: Tzoulas Konstantinos , Galan Juanjo , Venn Stephen , Dennis Matthew , Pedroli Bas , Mishra Himansu , Haase Dagmar , Pauleit Stephan , Niemelä Jari , James Philip
Published: September 2020

This article provides a perspective on nature-based solutions. First, the argument is developed that nature-based solutions integrate social and ecological systems. Then, theoretical considerations relating to relational values, multifunctionality, transdisciplinarity, and polycentric governance are briefly outlined. Finally, a conceptual model of the social–ecological system of nature-based solutions is synthesised and presented. This conceptual model comprehensively defines the social and ecological external and internal systems that make up nature-based solutions, and identifies theoretical considerations that need to be addressed at different stages of their planning and implementation The model bridges the normative gaps of existing nature-based solution frameworks and could be used for consistent, comprehensive, and transferable comparisons internationally. The theoretical considerations addressed in this article inform practitioners, policymakers, and researchers about the essential components of nature-based solutions. The conceptual model can facilitate the identification of social and ecological interconnections within nature-based solutions and the range of stakeholders and disciplines involved.
Study of Temporal Thermal Response of Microfiber Bragg Grating
Authors: Liao Changrui , Yang Tianhang , Han Jinli
Published: September 2020

Fiber Bragg grating has been successfully fabricated in the silica microfiber by the use of femtosecond laser point-by-point inscription. Temporal thermal response of the fabricated silica microfiber Bragg grating has been measured by the use of the CO2 laser thermal excitation method, and the result shows that the time constant of the microfiber Bragg grating is reduced by an order of magnitude compared with the traditional single-mode fiber Bragg grating and the measured time constant is ~ 21ms.
Age effect on tree structure and biomass allocation in Scots pine (Pinus sylvestris L.) and Norway spruce (Picea abies [L.] Karst.)
Authors: Hu Man , Lehtonen Aleksi , Minunno Francesco , Mäkelä Annikki
Published: September 2020

Key message

Tree structure equations derived from pipe model theory (PMT) are well-suited to estimate biomass allocation in Scots pine (Pinus sylvestrisL.) and Norway spruce (Picea abies[L.] Karst.). However, age dependence of parameters should be accounted for when applying the equations.

Context

Pipe model theory-based (PMT-based) structure equations have been incorporated in many process-based models. However, more data concerning old-growth trees is needed to test the reliability and generality of the structure equations.

Aims

This study (1) tested the age independence of the PMT-based structure equations and (2) provided general information about the stability of tree structure with age.

Methods

A total of 162 Scots pine and 163 Norway spruce trees in four age groups were analysed to test the age effect on the parameters of structure equations using a linear mixed model. Biomass of stem, branch and foliage was estimated from destructive measurements, and with other tree dimensions, they were used to present the tree growth patterns.

Results

(1) Stem biomass proportion increased with age, while branch and foliage biomass proportion decreased; biomass allocation and most tree variables became steady after maturing. (2) PMT-based structure equations were well-suited to Scots pine and Norway spruce in all age groups; however, age dependence was detected in the parameters of these equations, except for the branch-related equations in Scots pine and stem form coefficient below the crown base in both species.

Conclusion

Our study (1) provides information applicable to predictions of growth and biomass allocation in old boreal stands and (2) suggests taking age effect into account when structure equations are implemented in forest growth models.
Asthma in Competitive Cross-Country Skiers: A Systematic Review and Meta-analysis
Authors: Mäki-Heikkilä Rikhard , Karjalainen Jussi , Parkkari Jari , Valtonen Maarit , Lehtimäki Lauri
Published: September 2020

Introduction

In cross-country skiing, the repetitive ventilation of large amounts of cold and dry air strains the airways. The aim of this systematic review was to establish an overview of the current literature on asthma in cross-country skiers, biathletes and ski-orienteers.

Methods

Six databases were searched on August 29, 2019. The search yielded 2161 articles. Thirty articles fulfilled the search criteria and were pooled together for a qualitative synthesis. Eight articles were included in the meta-analysis on the prevalence of asthma and the use of asthma medication.

Results

According to the meta-analysis, the prevalence of self-reported physician-diagnosed asthma in skiers was 21% (95% CI 14–28%). The onset age of asthma was higher in skiers than in non-skiers with asthma. The prevalence of asthma medication use was on average 23% (CI 95% 19–26%). Several studies reported that asthma was underdiagnosed in skiers, as previously healthy skiers without a prior asthma diagnosis or medication use were frequently found to fulfill diagnostic criteria for asthma according to lung function tests. Studies using bronchial biopsy demonstrated that eosinophilic asthma is not detected in skiers with asthma as often as it is in non-skiers with asthma and that there are signs of airway inflammation even in non-asthmatic skiers.

Conclusion

Our findings suggest that the accuracy and coverage of diagnosing asthma in skiers has improved over the recent decades. However, the optimal treatment and natural course of asthma in this population remain unclear. Future research should investigate how the intensity of training, airway infections and their treatment affect the development of asthma among skiers.

PRD registration number

CRD42017070940.
Structural studies of the global networks exposed in the Panama papers
Authors: Kejriwal Mayank , Dang Akarsh
Published: September 2020

In recent history, the Panama Papers have comprised one of the largest and most influential leaks detailing information on offshore entities, company officers and financial (and legal) intermediaries, and has led to a global exposé of corruption and tax evasion. A systematic analysis of this information can provide valuable insights into the structure and properties of these entities and the relations between them. Network science can be applied as a scientific framework for understanding the structure of such relational, heterogeneous datasets at scale. In this article, we use an existing, relational version of the Panama Papers to selectively construct various networks, and then study the properties of the underlying system using well-defined analytical methods from network science, including degree properties, country assortativity analyses, connectivity and single-point network metrics like transitivity and density. We also illustrate significant structural features in these networks by conducting a triad census and exploring the networks’ core-periphery structure. Together, these results are used to show that the Panama Papers constitute a distinct class of networks that differ significantly from ordinary social and information networks. We also propose, construct and analyze ‘higher-order’ networks from the raw data, such as a ‘social’ network of officers. We confirm that some of these higher-order networks also show significant non-random deviations from expected or typical behavior, including in their degree distributions.
The transmission modes and sources of COVID-19: A systematic review
Authors: Rahman Heshu Sulaiman , Aziz Masrur Sleman , Hussein Ridha Hassan , Othman Hemn Hassan , Salih Omer Shirwan Hama , Khalid Eman Star , Abdulrahman Nusayba Abdulrazaq , Amin Kawa , Abdullah Rasedee
Published: September 2020

ABSTRACT

The current rampant coronavirus infection in humans, commonly known as COVID-19, a pandemic that may cause mortality in humans, has been declared a global emergency by the World Health Organization (WHO). The morbidity and mortality rates due to the pandemic are increasing rapidly worldwide, with the USA most affected by the disease. The source COVID-19 is not absolutely clear; however, the disease may be transmitted by either by COVID-19-positive individuals or from a contaminated environment. In this review, we focused on how the COVID-19 virus is transmitted in the community. An extensive literature search was conducted using specific keywords and criteria. Based on the published report, it is concluded that COVID-19 is primarily transmitted human-to-human via oral and respiratory aerosols and droplets with the virus-contaminated environment play a lesser role in the propagation of disease. Healthcare providers and the elderly with comorbidities are especially susceptible to the infection.

Highlights:
Just the Facts: Ovarian torsion in the emergency department setting
Authors: Long Brit , Targonsky Elisha , Koyfman Alex
Published: September 2020

A 23-year-old female presents with right lower quadrant pain that has been intermittent for the past several days. The pain suddenly worsened 1 hour ago. She denies vaginal bleeding or discharge, dysuria, fever, and back pain, but she has had several episodes of nausea with nonbloody, nonbilious vomiting. On examination, she is tender in the right lower quadrant, but her abdomen is not rigid.
Pilot test of an accrual Common Metric for the NIH Clinical and Translational Science Awards (CTSA) Consortium: Metric feasibility and data quality
Authors: Daudelin Denise H. , Peterson Laura E. , Selker Harry P.
Published: September 2020

Failure to accrue participants into clinical trials incurs economic costs, wastes resources, jeopardizes answering research questions meaningfully, and delays translating research discoveries into improved health. This paper reports the results of a pilot test of the Median Accrual Ratio (MAR) metric developed as a part of the Common Metrics Initiative of the NIH’s National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Award (CTSA) Consortium. Using the metric is intended to enhance the ability of the CTSA Consortium and its “hubs” to increase subject accrual into trials within expected timeframes. The pilot test was undertaken at Tufts Clinical and Translational Science Institute (CTSI) with eight CTSA Consortium hubs. We describe the pilot test methods, and results regarding feasibility of collecting metric data and the quality of data that was collected. Participating hubs welcomed the opportunity to assess accrual efforts, but experienced challenges in collecting accrual metric data due to insufficient infrastructure and inconsistent implementation of electronic data systems and lack of uniform data definitions. Also, the metric could not be constructed for all trial designs, particularly those using competitive enrollment strategies. We offer recommendations to address the identified challenges to facilitate progress to broad accrual metric data collection and use.
Using the payback framework to evaluate the outcomes of pilot projects supported by the Georgia Clinical and Translational Science Alliance
Authors: Rollins Latrice , Llewellyn Nicole , Ngaiza Manzi , Nehl Eric , Carter Dorothy R. , Sands Jeff M.
Published: September 2020

Introduction:

The Clinical and Translational Science Awards (CTSA) program of the National Center for Advancing Translational Sciences (NCATS) seeks to improve population health by accelerating the translation of scientific discoveries in the laboratory and clinic into practices for the community. CTSAs achieve this goal, in part, through their pilot project programs that fund promising early career investigators and innovative early-stage research projects across the translational research spectrum. However, there have been few reports on individual pilot projects and their impacts on the investigators who receive them and no studies on the long-term impact and outcomes of pilot projects.

Methods:

The Georgia CTSA funded 183 pilot projects from 2007 to 2015. We used a structured evaluation framework, the payback framework, to document the outcomes of 16 purposefully-selected pilot projects supported by the Georgia CTSA. We used a case study approach including bibliometric analyses of publications associated with the selected projects, document review, and investigator interviews.

Results:

These pilot projects had positive impact based on outcomes in five “payback categories”: (1) knowledge; (2) research targeting, capacity building, and absorption; (3) policy and product development; (4) health benefits; and (5) broader economic benefits.

Conclusions:

Results could inform our understanding of the diversity and breadth of outcomes resulting from Georgia CTSA-supported research and provide a framework for evaluating long-term pilot project outcomes across CTSAs.
Deployment and Operation of Outdoor Treatment Tents During the COVID-19 Pandemic
Authors: Peterson Keith H.J. , Muckey Erin Joy Cavin
Published: September 2020

The coronavirus disease 2019 (COVID-19) pandemic spread throughout the globe, with an alarming amount of new cases daily. To prepare for the inevitable patient surge, 1 hospital set up outdoor triage tents to assist with increased volume. Using the paradigm of space, staff, and stuff, an outdoor treatment area was designed and placed into operation. The patient volume in the treatment tents quickly grew with a 1-d max volume of 88 patients. Through the end of May 2020, a total of 2473 patients were seen and evaluated. As COVID-19 continues to spread and new areas of the United States and the world see spikes, it is imperative for the hospitals that previously dealt with a surge to disseminate the best practices they have learned during the pandemic.
Comparison of central-line–associated bloodstream infections between central venous catheters lined by combined chlorhexidine and silver sulfadiazine versus silver ionotrophes alone: A before–after–before retrospective study
Authors: Abouleish Youssef Z. , Oldfield Edward C. , Marik Paul E.
Published: September 2020

A before–after–before direct comparison between catheters lined with chlorhexidine and silver sulfadiazine (CHSS) versus silver ionotrophes (SI) with a primary objective of comparison of rate of central-line–associated infection (CLABSI) in three 10-month windows. The CHSS catheters were associated with a lower rate of CLABSI.
Collaborative Teams: Teachers, Parents, and Allied Health Professionals Supporting Students With Autism Spectrum Disorder in Mainstream Australian Schools
Authors: Vlcek Samantha , Somerton Michelle , Rayner Christopher
Published: September 2020

The unique traits and behaviours of students with autism spectrum disorder (ASD) often present a range of barriers to their educational experiences and development. The present study investigated collaborative partnerships between 3 stakeholders that often support students with ASD: teachers, parents, and allied health professionals (AHPs). With current literature on collaboration between teachers, parents, and AHPs involved in the education of students with ASD predominantly relating to specific skill or knowledge acquisition, there was an insufficient understanding of ‘collaborative processes’ and the factors that benefit or limit effective practice. In the present study, the researchers explored the experiences, processes, and opinions of parents, teachers, and AHPs supporting students with ASD in mainstream Australian primary schools. A total of 129 responses were recorded (41 teachers, 44 parents, and 44 AHPs) through an online survey, and thematic data analysis was used to qualitatively interpret the open-ended questions. The findings highlight the current opportunities and challenges faced by key stakeholders in this important process.
Protein malnutrition early in life increased apoptosis but did not alter the β-cell mass during gestation
Authors: Vial-Dahmer Daniela de Souza , da Rosa-Santos Chaiane Aline , Silva Luana Resende , Arantes Vanessa Cristina , de Barros Reis Marise Auxiliadora , Milanski Marciane , de Moura Egberto Gaspar , Lisboa Patrícia Cristina , Carneiro Everardo Magalhães , Damazo Amílcar Sabino , Latorraca Márcia Queiroz
Published: September 2020

We evaluated whether early-life protein restriction alters structural parameters that affect β-cell mass on the 15th day and 20th day of gestation in control pregnant (CP), control non-pregnant (CNP), low-protein pregnant (LPP) and low-protein non-pregnant (LPNP) rats from the fetal to the adult life stage as well as in protein-restricted rats that recovered after weaning (recovered pregnant (RP) and recovered non-pregnant). On the 15th day of gestation, the CNP group had a higher proportion of smaller islets, whereas the CP group exhibited a higher proportion of islets larger than the median. The β-cell mass was lower in the low-protein group than that in the recovered and control groups. Gestation increased the β-cell mass, β-cell proliferation frequency and neogenesis frequency independently of the nutritional status. The apoptosis frequency was increased in the recovered groups compared with that in the other groups. On the 20th day of gestation, a higher proportion of islets smaller than the median was observed in the non-pregnant groups, whereas a higher proportion of islets larger than the median was observed in the RP, LPP and CP groups. β-Cell mass was lower in the low-protein group than that in the recovered and control groups, regardless of the physiological status. The β-cell proliferation frequency was lower, whereas the apoptosis rate was higher in recovered rats compared with those in the low-protein and control rats. Thus, protein malnutrition early in life did not alter the mass of β-cells, especially in the first two-thirds of gestation, despite the increase in apoptosis.
Does unintended pregnancy have an impact on skilled delivery care use in Bangladesh? A nationally representative cross-sectional study using Demography and Health Survey data
Authors: Khan Md Nuruzzaman , Harris Melissa L. , Loxton Deborah
Published: September 2020

Skilled delivery care has been targeted in the Sustainable Development Goals to reduce preventable maternal and newborn deaths, which mostly occur because of birthing complications. Birthing complications are more frequent in women with unintended than intended pregnancies, and around 43% of total pregnancies in low- and middle-income countries are unintended. This study quantified the impact of unintended pregnancy on skilled birth attendance and delivery in health care facilities in Bangladesh. Data from 4493 women participating in the cross-sectional 2014 Bangladesh Demographic and Health Survey were analysed. Multilevel logistic regression models were used to assess the association of unintended pregnancy with skilled birth attendance and delivery in a health care facility through skilled providers while adjusting for individual-, household- and community-level factors identified using a directed acyclic graph. Around 26% of women reported that their last pregnancy (occurring within the previous 3 years) that ended with a live birth was unintended at conception. Only 42% reported having a skilled birth attendant present at their last birth and 38% gave birth in a health care facility. Significant differences were found across pregnancy intention. Lower odds of skilled birth attendance (OR, 0.70, 95% CI, 0.52–0.93) and delivery in a health care facility through skilled providers (OR, 0.65, 95% CI, 0.48–0.89) were found among women who had an unwanted pregnancy relative to women who had a wanted pregnancy. However, a mistimed pregnancy was not found to be associated with skilled birth attendance or delivery in health care facility through skilled providers. Increased availability of health care facilities at the community level is required in Bangladesh to ensure skilled delivery care for women with an unwanted pregnancy. Policies are also required to integrate women with an unwanted pregnancy into mainstream health care services through earlier detection and increased awareness in order to reduce the adverse maternal and fetal outcomes associated with lack of quality birthing care.
In vitro nematicidal activity of two ferrocenyl chalcones against larvae of Haemonchus contortus (L3) and Nacobbus aberrans (J2)
Authors: Vázquez-Bravo J. , Aguilar-Marcelino L. , Castañeda-Ramírez G.S. , De los Santos-Pérez I. , Arroyo-Carmona R.E. , Bernès S. , Hernández-Pareja U. , Gómez-Rodríguez O. , Rosas-Saito G.H.
Published: September 2020

The main goal of this work was to evaluate the in vitro biological activity of two ferrocenyl chalcones (FcC-1 and FcC-2) against Haemonchus contortus (third-stage larvae (L3)) and Nacobbus aberrans (second-stage juveniles (J2)). Both compounds were synthesized and characterized by usual spectroscopic methods and their molecular structures were confirmed by single-crystal X-ray diffractometry. Nematode strains were examined in terms of percentage mortality of H. contortus (L3) by the action of FcC-1, which showed an effectivity of 100% at a concentration of 342 μM in 24 h, with EC50 = 20.33 μM and EC90 = 162.76 μM, whereas FcC-2 had an effectivity of 72% at a concentration of 342 μM in 24 h, with EC50 = 167.39 μM and EC90 = 316.21 μM. The effect of FcC-1 against nematode phytoparasite N. aberrans showed a better percentage of 95% at a concentration of 342 μM, with EC50 = 7.18 μM and EC90 = 79.25 μM, whereas the effect of FcC-2 was 87% at 342 μM, with EC50 = 168 μM and EC90 = 319.56 μM at 36 h. After treatment, the scanning electron micrographs revealed deformities in the dorsal flank and posterior part close to the tail of H. contortus L3. They showed moderate in vitro nematicidal activity against H. contortus L3 and N. aberrans J2.
A laser-driven droplet source for plasma physics applications
Authors: Aurand Bastian , Aktan Esin , Schwind Kerstin Maria , Prasad Rajendra , Cerchez Mirela , Toncian Toma , Willi Oswald
Published: September 2020

In this paper, we report on the acceleration of protons and oxygen ions from tens of micrometer large water droplets by a high-intensity laser in the range of 1020 W/cm2. Proton energies of up to 6 MeV were obtained from a hybrid acceleration regime between classical Coulomb explosion and shocks. Besides the known thermal energy spectrum, a collective acceleration of oxygen ions of different charge states is observed. 3D PIC simulations and analytical models are employed to support the experiential findings and reveal the potential for further applications and studies.
What's taking so long? A collaborative method of collecting designers’ insight into what factors increase design effort levels in projects
Authors: Holliman Alexander Freddie , Thomson Avril , Hird Abigail , Wilson Nicky
Published: September 2020

Design effort is a key resource for product design projects. Environments where design effort is scarce, and therefore valuable, include hackathons and other time-limited design challenges. Predicting design effort needs is key to successful project planning; therefore, understanding design effort-influencing factors (objective considerations that are universally accepted to exert influence on a subject, that is, types of phenomena, constraints, characteristics, or stimulus) will aid in planning success, offering an improved organizational understanding of product design, characterizing the design space and providing a perspective to assess project briefs from the outset. This paper presents the Collaborative Factor Identification for Design Effort (CoFIDE) Method based on Hird's (2012) method for developing resource forecasting tools for new product development teams. CoFIDE enables the collection of novel data of, and insight into, the collaborative understanding and perceptions of the most influential factors of design effort levels in design projects and how their behavior changes over the course of design projects. CoFIDE also enables design teams, hackathon teams, and makerspace collaborators to characterize their creative spaces, to quickly enable mutual understanding, without the need for complex software and large bodies of past project data. This insight offers design teams, hackathon teams, and makerspace collaborators opportunities to capitalize on positive influences while minimizing negative influences. This paper demonstrates the use of CoFIDE through a case study with a UK-based product design agency, which enabled the design team to identify and model the behavior of four influential factors.
Cutting force prediction in ultrasonic-assisted milling of Ti–6Al–4V with different machining conditions using artificial neural network
Authors: Namlu Ramazan Hakkı , Turhan Cihan , Sadigh Bahram Lotfi , Kılıç S. Engin
Published: September 2020

Ti–6Al–4V alloy has superior material properties such as high strength-to-weight ratio, good corrosion resistance, and excellent fracture toughness. Therefore, it is widely used in aerospace, medical, and automotive industries where machining is an essential process for these industries. However, machining of Ti–6Al–4V is a material with extremely low machinability characteristics; thus, conventional machining methods are not appropriate to machine such materials. Ultrasonic-assisted machining (UAM) is a novel hybrid machining method which has numerous advantages over conventional machining processes. In addition, minimum quantity lubrication (MQL) is an alternative type of metal cutting fluid application that is being used instead of conventional lubrication in machining. One of the parameters which could be used to measure the performance of the machining process is the amount of cutting force. Nevertheless, there is a number of limited studies to compare the changes in cutting forces by using UAM and MQL together which are time-consuming and not cost-effective. Artificial neural network (ANN) is an alternative method that may eliminate the limitations mentioned above by estimating the outputs with the limited number of data. In this study, a model was developed and coded in Python programming environment in order to predict cutting forces using ANN. The results showed that experimental cutting forces were estimated with a successful prediction rate of 0.99 with mean absolute percentage error and mean squared error of 1.85% and 13.1, respectively. Moreover, considering too limited experimental data, ANN provided acceptable results in a cost- and time-effective way.
Underreporting COVID-19: the curious case of the Indian subcontinent
Authors: Biswas Raaj Kishore , Afiaz Awan , Huq Samin
Published: September 2020

COVID-19 has spread across the globe with higher burden placed in Europe and North America. However, the rate of transmission has recently picked up in low- and middle-income countries, particularly in the Indian subcontinent. There is a severe underreporting bias in the existing data available from these countries mostly due to the limitation of resources and accessibility. Most studies comparing cross-country cases or fatalities could fail to account for this systematic bias and reach erroneous conclusions. This paper provides several recommendations on how to effectively tackle these issues regarding data quality, test coverage and case counts.
Is the National Health Service a Religion?
Authors: Sandberg Russell
Published: September 2020

During the COVID-19 lockdown the initial British Government mantra of ‘Stay home. Protect the NHS. Save lives’, the ritualistic weekly public clapping for the National Health Service (NHS) and the overall tone of the media coverage led several commentators to raise the question of whether the NHS had become a religion. This question is legally significant. The question of whether the lockdown breached Article 9 has already been the subject of litigation. R (on the application of Hussain) v Secretary of State for Health [2020] EWHC 1392 (Admin) concerned the then prohibition on private prayer in places of worship. Swift J refused an application for interim relief to allow Friday prayers at Barkerend Road Mosque. Lockdown did infringe the claimant's Article 9 rights but this interference was only with one aspect of religious observance and the interference had a finite duration. The legitimate difference of opinion between the claimant and the British Board of Scholars and Imams was relevant to the question of justification. There was no real prospect that the claimant would succeed at obtaining a permanent injunction at trial because the pandemic presented ‘truly exceptional circumstances’ that meant that the interference would be justified on grounds of public health. Swift J was satisfied that there was a sufficiently arguable case to grant permission to apply for judicial review but he did not order that the claim be expedited. In Dolan, Monks and AB v Secretary of State for Health [2020] EWHC 1786 (Admin), an application of a judicial review of the lockdown regulations and schools closure was refused. However, in relation to Article 9, Lewis J adjourned consideration of this discrete issue because regulations had just been made that allowed communal worship which may have made the argument academic. English law provides the right to manifest religion or belief under the Human Rights Act 1998 and the right not to be discriminated against on grounds of religion or belief in relation to employment and the provision of goods and services under the Equality Act 2010. This raises the point: during the lifting of lockdown, when authorities require people to go back to their workplace or send their children to school, could individuals who refuse say they were legally entitled to decline on the basis that such a requirement breached their belief in protecting the NHS?
Vos estis lux mundi: Too Far or Not Far Enough?
Authors: Costigane Helen
Published: September 2020

In the light of the abuse crisis in the Roman Catholic Church, several inquiries have given recommendations on what should be done in the future, to ensure that such crimes are dealt with both civilly and canonically. In 2017, the Royal Commission of Australia produced a number of specific points to be addressed. Two years later, Pope Francis introduced guidelines to be observed universally whenever cases are reported, and these addressed many of the commission's recommendations. A question remains as to whether these have gone too far or far enough.
Drivers and health implications of the dietary transition among Inuit in the Canadian Arctic: a scoping review
Authors: Little Matthew , Hagar Hilary , Zivot Chloe , Dodd Warren , Skinner Kelly , Kenny Tiff-Annie , Caughey Amy , Gaupholm Josephine , Lemire Melanie
Published: September 2020

Objective:

The current study undertook a systematic scoping review on the drivers and implications of dietary changes among Inuit in the Canadian Arctic.

Design:

A keyword search of peer-reviewed articles was performed using PubMed, Web of Science, CINAHL, Academic Search Premier, Circumpolar Health Bibliographic Database and High North Research Documents. Eligibility criteria included all full-text articles of any design reporting on research on food consumption, nutrient intake, dietary adequacy, dietary change, food security, nutrition-related chronic diseases or traditional food harvesting and consumption among Inuit populations residing in Canada. Articles reporting onin vivoandin vitroexperiments or on health impacts of environmental contaminants were excluded.

Results:

A total of 162 studies were included. Studies indicated declining country food (CF) consumption in favour of market food (MF). Drivers of this transition include colonial processes, poverty and socio-economic factors, changing food preferences and knowledge, and climate change. Health implications of the dietary transition are complex. Micro-nutrient deficiencies and dietary inadequacy are serious concerns and likely exacerbated by increased consumption of non-nutrient dense MF. Food insecurity, overweight, obesity and related cardiometabolic health outcomes are growing public health concerns. Meanwhile, declining CF consumption is entangled with shifting culture and traditional knowledge, with potential implications for psychological, spiritual, social and cultural health and well-being.

Conclusions:

By exploring and synthesising published literature, this review provides insight into the complex factors influencing Inuit diet and health. Findings may be informative for future research, decision-making and intersectoral actions around risk assessment, food policy and innovative community programmes.
A review of clinical and emerging biomarkers for breast cancers: towards precision medicine for patients
Authors: Osei Ernest
Published: September 2020

Background:

Breast cancer is the most commonly diagnosed malignancy among women and accounts for about 25% of all new cancer cases and 13% of all cancer deaths in Canadian women. It is a highly heterogeneous disease, encompassing multiple tumour entities, each characterised by distinct morphology, behaviour and clinical implications. Moreover, different breast tumour subtypes have different risk factors, clinical presentation, histopathological features, outcome and response to systemic therapies. Therefore, any strategies capable of the stratification of breast cancer by clinically relevant subtypes are an important requirement for personalised and targeted treatment. Therefore, in the advancement towards the concept of precision medicine that takes individual patient variability into account, several investigators have focused on the identification of effective clinical breast cancer biomarkers that interrogate key aberrant pathways potentially targetable with molecular targeted or immunological therapies.

Methods and materials:

This paper reports on a review of 11 current clinical and emerging biomarkers used in screening for early detection and diagnosis, to stratify patients by disease subtype, to identify patients’ risk for metastatic disease and subsequent relapse, to monitor patient response to specific treatment and to provide clinicians the possibility of prospectively identifying groups of patients who will benefit from a particular treatment.

Conclusion:

The future holds promising for the use of effective clinical breast cancer biomarkers for early detection and personalised patient-specific targeted treatment and increased patient survival. Breast cancer biomarkers can potentially assist in early-staged, non-invasive, sensitive and specific breast cancer detection and screening, provide clinically useful information for identification of patients with a greater likelihood of benefiting from the specific treatment, offer a better understanding of the metastatic process in cancer patients, predict disease and for patients with the established disease can assist define the nature of the disease, monitor the success of treatment and guide the clinical management of the disease.
Detection of organic or inorganic material in Martian meteorite Zagami by vibrational spectroscopy?
Authors: do Nascimento-Dias Bruno Leonardo , Zucolotto Maria Elizabeth , Belgo Hugo Camarano , da Silva Talita Valverde Ferreira , dos Anjos Virgĩlio de Carvalho
Published: September 2020

Zagami is a basaltic shergottite well characterized among Martian meteorites. For this reason, it is used as a reference sample to verify the feasibility of the vibrational spectroscopy techniques. In general, these techniques seeking extract spectral signatures from individual mineral present in the meteorite samples. Among some FTIR results were detected organic compounds in the Zagami meteorite and recorded in some articles. Based on these results, an analysis of a Zagami meteorite sample was performed using FTIR and Raman spectrometry. Examining the fragment of Zagami meteorite using the FTIR technique, it was possible to identify the same band of 2920 and 2850 cm−1 described by other references, which were interpreted as organic components and were recorded such as aliphatic hydrocarbon. Another unusual result in Martian meteorite was the detection of the 1300 cm−1 band using Raman. The main reason for this peculiarity is that band is characterized in meteorites as a D band. Generally, this band is attributed to structural defects and the disordering of carbon. However, care should be taken when interpreting Raman spectra around 1300 cm−1 and FTIR spectra 2950–2840 cm−1 of the sample from oxidizing environments such as Mars. Misconceptions can occur during the interpretations of the bands, and this can lead to incorrect identification. Thus, an analysis of the mentioned peaks, such as chemical and mineralogical assignments, will be provided and suggested in order to compare the results that mentioned the presence of organic compounds in the Zagami meteorite.
What symptoms tell us: A multiple case study of oncology consultations
Authors: Bourquin Céline , Stiefel Friedrich
Published: September 2020

Objectives

While patients’ symptom experiences have been widely investigated, there is a lack of contextualized studies investigating how symptoms circulate in the medical consultation, how patients present them, what they convey, how physicians respond, and how patients and physicians negotiate with each other to find ways to address them. The aim of this study is to explore patients and physicians handling of symptoms throughout oncological consultations with a multiple case study approach.

Methods

Five consultations, purposively selected from an existing dataset of audiotaped consultations with patients with advanced cancer, were analyzed by means of an inductive analytical approach based on a sensitive framework from the literature.

Results

Patients’ symptoms showed multiple dimensions such as medical, cognitive, emotional, psychological, interactional, symbolic, experiential, and existential.

Significance of results

Different symptom dimensions remained unnoticed and unaddressed in the consultations. The physician-centered symptom approach that was observed leads to consumed time and missed opportunities for relationship building with the patient. Physicians showed a lack of sensitivity regarding the multiple dimensions of symptoms. Based on the findings, strategies for a more comprehensive symptom approach can be conceived.
Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
Authors: Voss Martin H. , Gordon Michael S. , Mita Monica , Rini Brian , Makker Vicky , Macarulla Teresa , Smith David C. , Cervantes Andrés , Puzanov Igor , Pili Roberto , Wang Ding , Jalal Shadia , Pant Shubham , Patel Manish R. , Neuwirth Rachel l. , Enke Aaron , Shou Yaping , Sedarati Farhad , Faller Douglas V. , Burris Howard A.
Published: September 2020

Background

This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTORC2, in advanced solid tumours.

Methods

Eligible patients received increasing sapanisertib doses once daily (QD; 31 patients), once weekly (QW; 30 patients), QD for 3 days on/4 days off QW (QD × 3dQW; 33 patients) or QD for 5 days on/2 days off QW (QD × 5dQW; 22 patients). In expansion cohorts, 82 patients with renal cell carcinoma (RCC), endometrial or bladder cancer received sapanisertib 5 mg QD (39 patients), 40 mg QW (26 patients) or 30 mg QW (17 patients).

Results

Maximum tolerated doses of sapanisertib were 6 mg QD, 40 mg QW, 9 mg QD × 3dQW and 7 mg QD × 5dQW. Frequent dose-limiting toxicities (DLTs) included hyperglycaemia, maculo-papular rash (QD), asthenia and stomatitis (QD × 3dQW/QD × 5dQW); expansion phase doses of 5 mg QD and 30 mg QW were selected based on tolerability beyond the DLT evaluation period. One patient with RCC achieved complete response; nine experienced partial responses (RCC: seven patients; carcinoid tumour/endometrial cancer: one patient each). Sapanisertib pharmacokinetics were time-linear and supported multiple dosing. Pharmacodynamic findings demonstrated treatment-related reductions in TORC1/2 biomarkers.

Conclusions

Sapanisertib demonstrated a manageable safety profile, with preliminary antitumour activity observed in RCC and endometrial cancer.

Clinical trial registration

ClinicalTrials.gov, NCT01058707.
Controlled coupling of an ultrapotent auristatin warhead to cetuximab yields a next-generation antibody-drug conjugate for EGFR-targeted therapy of KRAS mutant pancreatic cancer
Authors: Greene Michelle K. , Chen Ting , Robinson Eifion , Straubinger Ninfa L. , Minx Charlene , Chan Darren K. W. , Wang Jun , Burrows James F. , Van Schaeybroeck Sandra , Baker James R. , Caddick Stephen , Longley Daniel B. , Mager Donald E. , Straubinger Robert M. , Chudasama Vijay , Scott Christopher J.
Published: September 2020

Background

Antibody-drug conjugate (ADC) construction poses numerous challenges that limit clinical progress. In particular, common bioconjugation methods afford minimal control over the site of drug coupling to antibodies. Here, such difficulties are overcome through re-bridging of the inter-chain disulfides of cetuximab (CTX) with auristatin-bearing pyridazinediones, to yield a highly refined anti-epidermal growth factor receptor (EGFR) ADC.

Methods

In vitro and in vivo assessment of ADC activity was performed in KRAS mutant pancreatic cancer (PaCa) models with known resistance to CTX therapy. Computational modelling was employed for quantitative prediction of tumour response to various ADC dosing regimens.

Results

Site-selective coupling of an auristatin to CTX yielded an ADC with an average drug:antibody ratio (DAR) of 3.9, which elicited concentration- and EGFR-dependent cytotoxicity at sub-nanomolar potency in vitro. In human xenografts, the ADC inhibited tumour growth and prolonged survival, with no overt signs of toxicity. Key insights into factors governing ADC efficacy were obtained through a robust mathematical framework, including target-mediated dispositional effects relating to antigen density on tumour cells.

Conclusions

Together, our findings offer renewed hope for CTX in PaCa therapy, demonstrating that it may be reformatted as a next-generation ADC and combined with a predictive modelling tool to guide successful translation.
A systematic review of meta-analyses assessing the validity of tumour response endpoints as surrogates for progression-free or overall survival in cancer
Authors: Cooper Katy , Tappenden Paul , Cantrell Anna , Ennis Kate
Published: September 2020

Background

Tumour response endpoints, such as overall response rate (ORR) and complete response (CR), are increasingly used in cancer trials. However, the validity of response-based surrogates is unclear. This systematic review summarises meta-analyses assessing the association between response-based outcomes and overall survival (OS), progression-free survival (PFS) or time-to-progression (TTP).

Methods

Five databases were searched to March 2019. Meta-analyses reporting correlation or regression between response-based outcomes and OS, PFS or TTP were summarised.

Results

The systematic review included 63 studies across 20 cancer types, most commonly non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer. The strength of association between ORR or CR and either PFS or OS varied widely between and within studies, with no clear pattern by cancer type. The association between ORR and OS appeared weaker and more variable than that between ORR and PFS, both for associations between absolute endpoints and associations between treatment effects.

Conclusions

This systematic review suggests that response-based endpoints, such as ORR and CR, may not be reliable surrogates for PFS or OS. Where it is necessary to use tumour response to predict treatment effects on survival outcomes, it is important to fully reflect all statistical uncertainty in the surrogate relationship.