bluuebunny/crossref_metadata_2025 huggingface dataset:
Lean implementation within healthcare: imaging as fertile ground
Authors: Radcliffe Eloise , Kordowicz Maria , Mak Caroline , Shefer Guy , Armstrong David , White Patrick , Ashworth Mark
Published: October 2020

Purpose

The purpose of this paper is to understand the barriers and enablers to lean implementation as part of an imaging quality improvement programme from a socio-cultural perspective.

Design/methodology/approach

An in-depth 33 month ethnographic study, using observation and qualitative interviews, examined the process of lean implementation as part of an improvement programme.

Findings

Implementation of lean was more successful compared with other reports of lean in healthcare settings. Key enablers of lean were high levels of multidisciplinary staff involvement and engagement; the professional credibility of facilitators and clinicians as early adopters, all within a wider culture of relatively strong inter-professional relationships in the imaging department. These enablers combined with the more routinised and standardised nature of imaging pathways compared to some other acute specialties suggest that imaging is fertile ground for lean, linked to the manufacturing origins of lean.

Practical implications

When introducing lean within healthcare settings, special attention needs to be paid to the specific healthcare context and the existing cultures of inter-professional relationships. Fostering an improvement culture and engagement with training, together with adequate financial resource, are a key to contributing to the level of acceptability of an improvement tool such as lean.

Originality/value

This ethnographic study, bringing together rich multi-source data, has provided a detailed insight into the cultural workings of the process of lean implementation within a complex healthcare system.
A non-instantaneous inventory model of agricultural products considering deteriorating impacts and pricing policies
Authors: Hasan Md. Rakibul , Mashud Abu Hashan Md , Daryanto Yosef , Wee Hui Ming
Published: October 2020

Purpose

External factors such as improper handling, extreme weather and insect attacks affect product quality. It is most obvious in fruit products which have a high deterioration rate. Moreover, decaying fruits will increase the deteriorating of other good ones. The purpose of this study is to derive the optimal pricing and replenishment decisions for agricultural products considering the effect of external factors that induce deterioration.

Design/methodology/approach

In this paper, the study investigates ways to reduce the product deterioration rate by separating the near defective items from the other good products and accelerating the quick sales of the near defective items at a discounted price. The objective is to maximize the total profit by optimizing the selling price and the replenishment cycles. Two scenarios are investigated. In the first scenario, the retailer offers a selling price discount for near defective products to stimulate customer demand. In the second scenario, the retailer does not offer such discounts.

Findings

An algorithm to solve the model is derived. Further, numerical examples are developed to compare the total profit for the two scenarios. Theoretical derivations and graphical results show the concavity of the profit function. Finally, the sensitivity analysis shows that the total profit of the discount model is higher.

Originality/value

This study contributes to a new pricing and inventory decision model. The research provides insights to retailers on making optimal pricing and replenishment decisions for non-instantaneous deterioration items, as well as reducing the external factors that influence higher deterioration rate through separating good products from the near defective ones which are sold at a discount to induce the sale.
Influence of roadways on heavy metal content in soils and yerba mate tissue in southern Brazil
Authors: Frigo Cleiton , Magri Ederlan , Barbosa Julierme Zimmer , Sarteretto Laudete Maria , Araujo Eloá Moura , Melo Vander Freitas de , Prior Stephen Arthur , Motta Antônio Carlos Vargas
Published: October 2020

Purpose

Vehicular road traffic may represent an important soil and plant contamination source. In this context, the concentration of heavy metals (Cd, Pb, As, Sb, Ni, Cu, Fe, Al, Mn and Zn) and macronutrients (Ca, Mg, K and P) was evaluated in yerba mate (Ilex paraguariensis St. Hil.) cultivations and in soils adjacent to highways.

Design/methodology/approach

The investigated yerba mate cultivations were located in southern Brazil. Plant tissue (young and old leaves and branches) and soil (0–10 cm) samples were collected at five distances from the highway (0–10, 10–20, 20–30, 30–40 and 40–50 m). Plant tissue was analyzed with and without washing to evaluate contributions from particulate deposition.

Findings

Although increases in soil pseudo-total concentrations of Cd, Cu, Ni, Zn, Fe, Mn, Ca and Mg were observed only at the Erechim site, geoaccumulation indices and enrichment factors (EFs) did not indicate any heavy metal pollution. These results indicate the existence of natural variation in soil. Cadmium was more concentrated in branches than in leaves, while the opposite was observed for Pb. High levels of Mn and Al were found in foliar tissue. In summary, highway proximity did not lead to heavy metal contamination of yerba mate under the evaluated conditions.

Originality/value

This research explores the possibility of heavy metal pollution in plantations of yerba mate adjacent to highways and indicates natural concentrations of toxic elements that exceed current legislation, which was an important discovery regarding the yerba mate production chain.
Behavioural responses to warming differentially impact survival in introduced and native dung beetles
Authors: Mamantov Margaret A. , Sheldon Kimberly S.
Published: October 2020

Anthropogenic changes are often studied in isolation but may interact to affect biodiversity. For example, climate change could exacerbate the impacts of biological invasions if climate change differentially affects invasive and native species. Behavioural plasticity may mitigate some of the impacts of climate change, but species vary in their degree of behavioural plasticity. In particular, invasive species may have greater behavioural plasticity than native species since plasticity helps invasive species establish and spread in new environments. This plasticity could make invasives better able to cope with climate change.

Here our goal was to examine whether reproductive behaviours and behavioural plasticity vary between an introduced and a nativeOnthophagusdung beetle species in response to warming temperatures and how differences in behaviour influence offspring survival.

Using a repeated measures design, we exposed small colonies of introducedO. taurusand nativeO. hecateto three temperature treatments, including a control, low warming and high warming treatment, and then measured reproductive behaviours, including the number, size and burial depth of brood balls. We reared offspring in their brood balls in developmental temperatures that matched those of the brood ball burial depth to quantify survival.

We found that the introducedO. taurusproduced more brood balls and larger brood balls, and buried brood balls deeper than the nativeO. hecatein all treatments. However, the two species did not vary in the degree of behavioural plasticity in response to warming. Differences in reproductive behaviours did affect survival such that warming temperatures had a greater effect on survival of offspring of nativeO. hecatecompared to introducedO. taurus.

Overall, our results suggest that differences in behaviour between native and introduced species are one mechanism through which climate change may exacerbate negative impacts of biological invasions.
Symbiotic soil fungi enhance resistance and resilience of an experimental grassland to drought and nitrogen deposition
Authors: Jia Yangyang , van der Heijden Marcel G. A. , Wagg Cameron , Feng Gu , Walder Florian
Published: October 2020

Ecosystem stability is threatened by multiple global change factors such as drought and elevated nitrogen deposition. Yet, it is still poorly understood whether soil organisms can buffer against such perturbations. Here we focus on arbuscular mycorrhizal fungi (AMF), a common and widespread group of soil fungi. AMF form symbiotic associations with the majority of terrestrial land plants and promote a range of ecosystem services including plant production, diversity and nutrient cycling.

We tested whether AMF have the ability to enhance the resistance and resilience of plant communities under soil moisture deficit (hereby drought) and nitrogen deposition. Grassland microcosms with 11 different plant species were established with and without AMF and exposed to elevated nitrogen levels and to an intermittent period of drought.

Drought strongly reduced plant productivity and nitrogen cycling, but had limited effects on plant diversity. Nitrogen enrichment reduced plant diversity and increased nitrogen leaching and N2O emissions. The presence of AMF enhanced plant productivity, plant diversity and reduced nitrogen losses. AMF facilitated the resistance of plant productivity and nitrogen cycling to drought and the recovery of the plant community structure back to its pre drought state. Furthermore, AMF also mitigated the adverse effects of nitrogen enrichment on the resistance of multiple ecosystem functions to drought.

Synthesis. Our work highlights the integral role of AMF for the stability of ecosystem functioning; AMF are not only able to promote resistance to harsh conditions of global change but also improve resilience by enabling plant communities to recover. These findings underline AMF's insurance capacity to buffer ecosystems against global change.
Time to antimicrobial therapy in septic shock patients treated with an early goal‐directed resuscitation protocol: A post‐hoc analysis of the ARISE trial
Authors: Bulle Esther B , Peake Sandra L , Finnis Mark , Bellomo Rinaldo , Delaney Anthony ,   on behalf of the ARISE Investigators,   ARISE Investigators
Published: October 2020

Objective

Intravenous antimicrobial therapy within 1 h of the diagnosis of septic shock is recommended in international sepsis guidelines. We aimed to evaluate the association between antimicrobial timing and mortality in patients presenting to the ED with septic shock.

Methods

Post‐hoc analysis of 1587 adult participants enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) multicentre trial of early goal‐directed therapy for whom the time of initial antimicrobial therapy was recorded. We compared participants who had initiation of antimicrobials within the first hour (early) or later (delayed) of ED presentation. A propensity score model using inverse probability of treatment weighting was constructed to account for confounding baseline covariates. The primary outcome was 90‐day mortality.

Results

The median (interquartile range) time to initiating antimicrobials was 69 (39–112) min with 712 (44.9%) participants receiving the first dose within the first hour of ED presentation. Compared with delayed therapy, early administration was associated with increased baseline illness severity score and greater intensity of resuscitation pre‐randomisation (fluid volumes, vasopressors, invasive ventilation). All‐cause 90‐day mortality was also higher; 22.6% versus 15.5%; unadjusted odds ratio (OR) 1.58 (95% confidence interval [CI] 1.16–2.15), P = 0.004. After inverse probability of treatment weighting, the mortality difference was non‐significant; OR 1.30 (95% CI 0.95–1.76), P = 0.1. Live discharge rates from ICU (OR 0.81, 95% CI 0.72–0.91; P = 0.80) and hospital (OR 0.93, 95% CI 0.82–1.06; P = 0.29) were also not different between groups.

Conclusion

In this post‐hoc analysis of the ARISE trial, early antimicrobial therapy was associated with increased illness severity, but 90‐day adjusted mortality was not reduced.
Institutional and cross‐institutional research clusters: A community detection analysis of #IAG2019Hobart
Authors: Williamson Wayne
Published: October 2020

Academic conferences create an opportunity to disseminate new research, network with like‐minded researchers, and make new connections. The use of Twitter at these conferences continues to expand. This article focuses on how the Twitter data generated during conferences can be visually analysed in terms of community detection, connectivity, and information flows. Using social network analysis techniques and an online survey, the article analyses the subgroups within the entire network, their institutional affiliations, and research interest, and then focuses on the roles of the highly connected Twitter uses in the network. Through in‐depth analysis, the data revealed both how Australian geography academics use Twitter during a conference and how they cluster based on affiliations and research interest and also identified the information bridges in the social media conference network generated by using #IAG2019Hobart. The article concludes with some recommendations for further research.
Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway
Authors: Gai Hongyu , Zhou Fang , Zhang Yuxin , Ai Jingya , Zhan Jicheng , You Yilin , Huang Weidong
Published: October 2020

Impaired lipid and glucose metabolism in the liver is a crucial characteristic of nonalcoholic fatty liver disease (NAFLD). Coniferaldehyde (CA), a kind of phenolic compound found in many edible plants, has multiple biological and pharmacological functions. However, since the effect and molecular mechanism of CA on hepatic lipid and glucose metabolism disorders in NAFLD remain unknown, this study investigated its impact on the lipid and glucose metabolism of palmitic acid (PA)‐induced HepG2 cells. Compared with the HepG2 cells treated only with PA, supplementation with 25, 50, and 100 µM CA reduced the levels of intracellular triglyceride (by 7.11%, 19.62%, and 31.57%) and total cholesterol (by 8.46%, 23.32%, and 27.17%), and enhanced glucose uptake (by 40.91%, 57.49%, and 61.32%) and intracellular glycogen content (by 12.75%, 41.27%, and 53.77%). Moreover, CA supplementation downregulated the expression of sterol regulatory element‐binding protein‐1, fatty acid synthase, and stearoyl‐CoA desaturase 1 related to lipogenesis while upregulating the expression of carnitine palmitoyltransferase 1α related to fatty acid oxidation. CA supplementation also upregulated the glucose transporter 2 protein expression and phosphorylation of glycogen synthase kinase 3β while downregulating the phosphorylation of glycogen synthase. Most importantly, most of these effects of CA were reversed by pretreatment with AMP‐activated protein kinase (AMPK) inhibitor and small interfering RNA‐liver kinase B1 (LKB1). In conclusion, CA ameliorated the lipid and glucose metabolism in PA‐induced HepG2 cells via the LKB1/AMPK signaling pathway.

Practical Application

In this study, coniferaldehyde appeared to be effective in ameliorating hepatic lipid and glucose metabolism disorders in nonalcoholic fatty liver disease by reducing the levels of intracellular triglyceride and total cholesterol and enhancing glucose uptake and intracellular glycogen content via the LKB1/AMPK signaling pathway in vitro. Therefore, our findings provide new evidence in support of that supplementation with coniferaldehyde or food rich in coniferaldehyde might be considered as a viable dietary intervention strategy for preventing and treating nonalcoholic fatty liver disease.
Investigation of physicochemical, nutritional, and sensory qualities of muffins incorporated with dried brewer's spent grain flours as a source of dietary fiber and protein
Authors: Shih Yi‐Ting , Wang Wenjun , Hasenbeck Aimee , Stone Dave , Zhao Yanyun
Published: October 2020

Brewers' spent grain (BSG) is the major byproduct of brewing beer, rich in protein and dietary fiber. This study investigated the effect of two drying methods (impingement and hot‐air drying) on chemical composition, physicochemical properties, and bioactive compounds of BSGs from three different brewers (BSG1, BSG2, and BSG3), and then evaluated the quality and consumer acceptance of BSG flour fortified muffins. Results showed that impingement drying led to significantly lower moisture content (MC, 1.33‐1.87 g/100g) and water activity (aw, 0.04‐0.07) of BSGs than hot‐air drying (5.44 to 5.57 g/100 g and 0.19 to 0.20, respectively). Among different dried BSGs, impingement dried BSG3 achieved the highest protein (18.03 g/100 g dry matter [DM]), total phenolic content (TPC, 2.21 mg GAE/g DM), radical scavenging activity (RSA, 1.58 mg AAE/g DM), and total flavonoid content (TFC, 0.68 mg QE/g DM), and retained lighter color (L*, 54.68) and higher total dietary fiber (TDF, 42.40 g/100 g DM), which was selected for making BSG‐fortified muffins. BSG3 was substituted 1:1 as white: whole wheat flour at three concentrations (10, 15, and 20 g/100 g flour mix) for muffins (BSG10, BSG15, and BSG20, respectively). BSG15 provided higher protein (13.11 g/100 g DM), TDF (16.88 g/100 g DM), and higher bioactive compounds compared to control and retained brighter color of muffin compared to BSG20, showing no difference in firmness and overall liking compared to the control muffin. This study demonstrated that impingement dried BSG could be utilized as a functional ingredient in muffins to add value to the food chain providing nutritional and environmental benefits.

Practical Application

This study reported the benefit of impingement drying method for the retention of physicochemical quality and bioactive compounds of brewer's spent grains (BSG) produced from three different brewers in comparison with hot‐air drying. The study also reported that muffins fortified with BSG flours (15% replacement of wheat flour) yielded a 23% increase in total dietary fiber and 13% increase in protein without affecting consumer acceptance of the products. This information is essential for developing value‐added applications of BSG, a byproduct from brewing industry, as a functional ingredient to make nutritive baking goods, such as muffins, for promoting human health.
Acoustically‐aided osmo‐dehydration pretreatments under pulsed vacuum dryer for apple slices: drying kinetics, thermodynamics, and quality attributes
Authors: Amanor‐Atiemoh Robert , Zhou Cunshan , Wahia Hafida , Mustapha Abdullateef Taiye , Rashid Muhammad Tayyab , Sampson Gilbert , Amoa‐Owusu Abigail , Ma Haile , Zhou Ruoyu
Published: October 2020

The research work investigates the effect of different pretreatment conditions (osmotic dehydration [OD], ultrasound [US], and ultrasound‐assisted osmotic dehydration [UOD]) on the drying kinetics modeling, thermodynamics, weight reduction, degradation kinetics of vitamin C, and color of apple slices under pulsed vacuum dryer (PVD). The findings showed that UOD pretreatment significantly improved drying time and increased weight reduction comparative to OD, US, and the control sample. Drying kinetics modeling revealed that the Hii model better described the drying kinetic behavior of the apple slices than the other nine mathematical models based on higher coefficient of determination (R2), root mean square error (RMSE), and reduced chi‐square (χ2). Analysis of vitamin C content revealed a 46.05%, 31.28%, and 25.95% retention for UOD, US, and OD, respectively, after drying. Second‐order kinetics could accurately predict the degradation kinetics of vitamin C compared to first‐order kinetics. Vitamin C degradation kinetics showed lowerk‐value, higherD‐value (time required for 90% degradation), and half‐life indicating a higher retention of vitamin C content for UOD pretreatment compared to OD and US during drying.L*,b*, and chroma values of UOD were significantly (P< 0.05) higher compared to US, OD, and the control sample.

Practical Application

The findings of this study revealed that ultrasonic‐aided osmotic dehydration is a unique and novel pretreatment technique prior to drying, which significantly shortens drying time as a result of faster moisture/mass transfer, improves processing efficiency thereby reducing processing cost, improves quality parameters, and preserve phytochemicals. This makes the business operations of food processors competitive and as well provide value for customers.
Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof‐of‐concept study
Authors: Cornejo Rodrigo , Iturrieta Pablo , Olegário Tayran M. M. , Kajiyama Carolina , Arellano Daniel , Guiñez Dannette , Cerda María A. , Brito Roberto , Gajardo Abraham I. J. , Lazo Marioli , López Lorena , Morais Caio C. A. , González Sedric , Zavala Miguel , Rojas Verónica , Medel Juan N. , Hurtado Daniel E. , Bruhn Alejandro , Ramos Cristobal , Estuardo Nivia
Published: October 2020

Rationale

Cyclic strain may be a determinant of ventilator‐induced lung injury. The standard for strain assessment is the computed tomography (CT), which does not allow continuous monitoring and exposes to radiation. Electrical impedance tomography (EIT) is able to monitor changes in regional lung ventilation. In addition, there is a correlation between mechanical deformation of materials and detectable changes in its electrical impedance, making EIT a potential surrogate for cyclic lung strain measured by CT (StrainCT).

Objectives

To compare the global StrainCT with the change in electrical impedance (ΔZ).

Methods

Acute respiratory distress syndrome patients under mechanical ventilation (VT 6 mL/kg ideal body weight with positive end‐expiratory pressure 5 [PEEP 5] and best PEEP according to EIT) underwent whole‐lung CT at end‐inspiration and end‐expiration. Biomechanical analysis was used to construct 3D maps and determine StrainCT at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between StrainCT and ΔZ. Linear regression models were used to predict the change in lung StrainCT between different PEEP levels based on the change in ΔZ.

Main results

StrainCT was positively and independently associated with ΔZ at global level (P < .01). Furthermore, the change in StrainCT (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R2 0.855, P < .001 at global level) with a high agreement between predicted and measured StrainCT.

Conclusions

The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.
On goodness‐of‐fit measures for Poisson regression models
Authors: Kurosawa Takeshi , Hui Francis K.C. , Welsh A.H. , Shinmura Kousuke , Eshima Nobuoki
Published: October 2020

In this article, we study the statistical properties of the goodness‐of‐fit measure mpp proposed by (Eshima & Tabata 2007, Statistics & Probability Letters 77, 583–593) for generalised linear models. Focusing on the special case of Poisson regression using the canonical log link function, and assuming a random vector X of covariates, we obtain an explicit form for mpp that enables us to study its properties and construct a new estimator for the measure by utilising information about the shape of the covariate distribution. Simulations show that the newly proposed estimator for mpp exhibits better performance in terms of mean squared error than the simple unbiased covariance estimator, especially for larger absolute values of the slope coefficients. In contrast, it may be more unstable when the value of the slope coefficient is close to boundary of the domain of the moment generating function for the corresponding covariate. We illustrate the application of mpp on a data set of counts of complaints against doctors working in an emergency unit in hospital, in particular, showing how our proposed estimator can be efficiently computed across a series of candidate models.
Primary HPV screening for cervical cancer: Results after two screening rounds in a regional screening program in Finland
Authors: Veijalainen Olga , Kares Saara , Kotaniemi‐Talonen Laura , Kujala Paula , Vuento Risto , Luukkaala Tiina , Kholová Ivana , Mäenpää Johanna
Published: October 2020

Introduction

Since 2012, cervical cancer screening has been conducted with a primary high‐risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high‐grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test.

Material and methods

The primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low‐grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV‐positive women with a negative or equivocal cytology triage were re‐screened after approximately 12‐16 months. hrHPV‐negative women were scheduled for re‐screening after 5 years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35‐55 years old in 2012, and 40‐60 years old in 2017.

Results

In all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5 years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35‐ to 55‐year age cohort. In 2017, 4807 (73%) of the women aged 40‐60 years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P = .002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P = .220).

Conclusions

In the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test.
Rising trends in the incidence of shoulder dystocia and development of a novel shoulder dystocia risk score tool: a nationwide population‐based study of 800 484 Finnish deliveries
Authors: Heinonen Karin , Saisto Terhi , Gissler Mika , Kaijomaa Marja , Sarvilinna Nanna
Published: October 2020

Introduction

Shoulder dystocia has remained an unpredictable and feared emergency in obstetrics. Some risk factors have been identified but nevertheless there is a lack of risk evaluation tools in clinical practice. The aim of this study was to evaluate the incidence and risk factors of shoulder dystocia in the Finnish population and to develop a shoulder dystocia risk score tool.

Material and methods

This retrospective, population‐based study included all deliveries in Finland between 2004 and 2017 (n = 800 484). The annual numbers of shoulder dystocia diagnoses were gathered from nationwide Finnish Medical Birth Register and Hospital Discharge Register. The incidence of shoulder dystocia was calculated in subgroups according to the mode of delivery, maternal diabetes status, body mass index (BMI), age, parity and gestational age. Based on these numbers, a shoulder dystocia risk score tool was created.

Results

The overall incidence of shoulder dystocia was 0.18%. It increased significantly during the study period from 0.10% to 0.32% (P < .001). More specifically, the incidence increased significantly in all analyzed subgroups except for women with BMI <18.5 or age <20 years. To evaluate the importance of risk factors, practical and simple shoulder dystocia risk score tool was created. Instrumental vaginal delivery, maternal diabetes of any kind, BMI ≥25, age ≥40 years and gestational age ≥41 weeks were associated with higher shoulder dystocia risk compared with non‐diabetic, non‐obese and younger women with spontaneous deliveries before 41 weeks of gestation. In our risk score tool, cases with shoulder dystocia had a significantly higher number of risk points than those without it (15.2 vs 10.4, P < .001). The risk was significantly high when the scores were ≥18 points (relative risk 9.54, 95% confidence interval 8.61‐10.57).

Conclusions

The incidence of shoulder dystocia in Finland increased during the study period but it is still low compared with previous studies from other countries. In clinical daily practice, the new shoulder dystocia risk score tool helps to evaluate the individual risk profile of the parturient. According to this risk score tool, the highest risk was found with the combination of instrumental vaginal delivery, maternal diabetes, BMI ≥25, age ≥40 years and gestational age ≥41 weeks.
Addressing the controversial origin of the marble source used in the Phoenician anthropoid sarcophagi of Gadir (Cadiz, Spain)
Authors: Lapuente P. , Rodà I. , Gutiérrez Garcia‐M A. , Brilli M.
Published: October 2020

Dating from the fifth century bce, two Phoenician anthropoid sarcophagi, a male and a female, found in Gadir (Cadiz, Spain), are so far the most ancient marble sculptures found in the Iberian Peninsula. The identification of the source of the marble used to produce them has been a subject of controversy for several decades and has recently resurfaced when it was published that they were made by Phoenician artisans using Iberian marble from Macael. This identification is not only unreasonable from an archaeological point of view but also unsupported by any analytical data. On the contrary, as the sarcophagi belong to an Eastern Mediterranean Sidonian production, their raw material is most likely to be Greek–Minor Asian in origin. In order to shed a light on this dispute and objectively resolve the provenance of the marble, a multi‐method analytical approach was carried out. Optical microscopy, cathodoluminescence analyses, and C and O stable isotopes clarify the provenance of the marble, confirming that both singular sarcophagi were carved in a Cycladic marble, in accordance with their Sidonian style.
Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B‐lymphoblastic leukaemia: Ma‐Spore ALL 2010 study
Authors: Jiang Nan , Wang Lingzhi , Xiang Xiaoqiang , Li Zhenhua , Chiew Edwynn Kean Hui , Koo Yok Moi , Lee How Sung , Lin Hai Peng , Tan Ah Moy , Quah Thuan Chong , Kham Shirley Kow Yin , Goh Boon Cher , Ariffin Hany , Yeoh Allen Eng‐Juh
Published: October 2020

Aims

Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up‐front window of Ma‐Spore ALL 2010 (MS2010) study.

Methods

We randomised 429 children with newly diagnosed ALL to 15‐minute vs 3‐hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B‐ALL and 20 T‐ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed.

Results

There was no significant difference between 15‐minute and 3‐hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B‐ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild‐type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT.

Conclusion

We showed that in childhood B‐ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.
Comparison of the efficacy and safety of different doses of nifekalant in the instant cardioversion of persistent atrial fibrillation during radiofrequency ablation
Authors: Zhai Zhenyu , Xia Zirong , Xia Zhen , Hu Jinzhu , Hu Jianxin , Zhu Bo , Xiong Qinmei , Wu Yanqing , Hong Kui , Chen Qi , Yu JianHua , Li Juxiang
Published: October 2020

Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single‐centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end‐point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end‐point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end‐point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end‐point: The rates of the majority of other common drug‐related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit‐risk profile.
Prevention of suicidal behavior in bipolar disorder
Authors: Tondo Leonardo , Vázquez Gustavo H. , Baldessarini Ross J.
Published: October 2020

Background

Excess mortality is a critical hallmark of bipolar disorder (BD) due to co‐occurring general medical disorders and especially from suicide. It is timely to review of the status of suicide in BD and to consider the possibility of limiting suicidal risk.

Methods

We carried out a semi‐systematic review of recent research reports pertaining to suicide in BD.

Findings

Suicide risk in BD is greater than with most other psychiatric disorders. Suicide rates (per 100,000/year) are approximately 11 and 4 in the adult and juvenile general populations, but over 200 in adults, and 100 among juveniles diagnosed with BD. Suicide attempt rates with BD are at least 20 times higher than in the adult general population, and over 50 times higher among juveniles. Notable suicidal risk factors in BD include: previous suicidal acts, depression, mixed–agitated‐dysphoric moods, rapid mood‐shifts, impulsivity, and co‐occurring substance abuse. Suicide‐preventing therapeutics for BD remain severely underdeveloped. Evidence favoring lithium treatment is stronger than for other measures, although encouraging findings are emerging for other treatments.

Conclusions

Suicide is a leading clinical challenge for those caring for BD patients. Improved understanding of risk and protective factors combined with knowledge and close follow‐up of BD patients should limit suicidal risk. Ethically appropriate and scientifically sound studies of plausible medicinal, physical, and psychosocial treatments aimed at suicide prevention specifically for BD patients are urgently needed.
Novel mechanism of action for the mood stabilizer lithium
Authors: Abu‐Hijleh Fahed A. , Prashar Shreya , Joshi Hetshree , Sharma Roohie , Frey Benicio N. , Mishra Ram K.
Published: October 2020

Background

Bipolar Disorder (BD) is associated with a decrease in cellular resilience. Despite the half a century old discovery of lithium's efficacy for the treatment of BD, its exact mechanisms remain elusive. Accumulating data suggest that lithium's cytoprotective properties involve the modulation of several UPR proteins, such as GRP78. Mesencephalic astrocyte‐derived neurotrophic factor (MANF) is an endoplasmic reticulum resident protein that regulates proteostasis through directly interacting with GRP78. The purpose of this study was to determine whether lithium increases MANF expression using cellular and rodent models and, if so, to elucidate the cellular mechanisms of action.

Procedure

Mouse striatal neuroblasts were treated with PBS, lithium, or lithium + Activator Protein‐1 (AP‐1) inhibitor for 24–72 hours. Once cells were harvested, mRNA was extracted. In vivo experiments included, intraperitoneal injections of lithium or saline to male Sprague Dawley rats twice daily for 14 consecutive days. Following drug treatment, brain tissue was isolated, and mRNA was extracted from various regions. MANF gene expression was measured using RT‐qPCR.

Results

In vitro studies showed lithium‐treated cells displayed a significant increase in MANF mRNA expression compared to controls. In contrast, cells treated with lithium and AP‐1 inhibitor showed no increase in expression. Similarly, in vivo studies revealed that lithium‐treated rats compared to controls had a significant increase in MANF expression in the PFC and striatum.

Conclusion

Taken together, these data suggest that lithium's therapeutic mechanism involves the maintenance of ER homeostasis via increased MANF gene expression mediated by the AP‐1 transcription factor.
Best practices in ethics management: Insights from a qualitative study in Slovakia
Authors: Lašáková Anna , Remišová Anna , Bohinská Alexandra
Published: October 2020

Voluminous growth of new ethics management elements in corporate practice implies the need to enrich its theoretical understanding. Most studies delineate ethics management conventionally as measures primarily applied for establishing ethical norms and employee compliance. Furthermore, many models are somewhat limited in scope and amount of presented practices and usually do not conceptualize ethics management functions beyond traditional compliance‐integrity discussion. In addition, most models are not grounded in empirical research. With the aim to contribute to ethics management theory and bridge it with practice, this study employs a constructivist approach and maps best practices in ethics management via four focus groups with management professionals. Results suggest that ethics management can be viewed as a fundamentally participative and collaborative process, as a way of building relationships with external stakeholders, balancing structured planning and flexible change, and profoundly amalgamating with human resource management processes. Furthermore, in an Inventory of best practices encompassing 70 ethics practices, this study outlines nine functional subprocesses as key aspects of ethics management’s practical implementation. As the research was conducted in Slovakia, this study provides unique information on the recent developments in ethics management in one of the post‐transitional countries in the region of Central and Eastern Europe.
CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression
Authors: Yanai Yoshinori , Kosaka Takeo , Nakamura Kohei , Aimono Eriko , Matsumoto Kazuhiro , Morita Shinya , Mikami Shuji , Nishihara Hiroshi , Oya Mototsugu
Published: October 2020

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.
Efficacy of the novel tubulin polymerization inhibitor PTC‐028 for myelodysplastic syndrome
Authors: Zhong Cheng , Kayamori Kensuke , Koide Shuhei , Shinoda Daisuke , Oshima Motohiko , Nakajima‐Takagi Yaeko , Nagai Yurie , Mimura Naoya , Sakaida Emiko , Yamazaki Satoshi , Iwano Satoshi , Miyawaki Atsushi , Ito Ryoji , Tohyama Kaoru , Yamaguchi Kiyoshi , Furukawa Yoichi , Lennox William , Sheedy Josephine , Weetall Marla , Iwama Atsushi
Published: October 2020

Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors. The novel small molecule PTC596 directly binds tubulin, inhibits microtubule polymerization, downregulates MCL‐1, and induces p53‐independent apoptosis in acute myeloid leukemia cells. We herein investigated the efficacy of PTC‐028, a structural analog of PTC596, for myelodysplastic syndrome (MDS). PTC‐028 suppressed growth and induced apoptosis in MDS cell lines. The efficacy of PTC028 in primary MDS samples was confirmed using cell proliferation assays. PTC‐028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit growth and induce apoptosis in MDS cells. Mechanistically, a treatment with PTC‐028 induced G2/M arrest followed by apoptotic cell death. We also assessed the efficacy of PTC‐028 in a xenograft mouse model of MDS using the MDS cell line, MDS‐L, and the AkaBLI bioluminescence imaging system, which is composed of AkaLumine‐HCl and Akaluc. PTC‐028 prolonged the survival of mice in xenograft models. The present results suggest a chemotherapeutic strategy for MDS through the disruption of microtubule dynamics in combination with DNA hypomethylating agents.
TET2: A cornerstone in normal and malignant hematopoiesis
Authors: Kunimoto Hiroyoshi , Nakajima Hideaki
Published: October 2020

Regulation of genome‐wide DNA methylation is fundamental for a variety of biological processes such as mammalian development, stem cell function, cellular proliferation/differentiation, and oncogenesis. Among the regulators of DNA methylation, ten‐eleven translocation 2 (TET2) is one of the most frequently mutated genes in clonal hematopoiesis of indeterminate potential and in various hematological malignancies, underscoring a pivotal role for TET2 in blood homeostasis and hematopoietic transformation. TET2 oxidizes methylated cytosines to further modify cytosines, which behave as intermediates in active/passive DNA demethylation processes. TET2 itself associates with histone modifiers, thereby regulating histone modifications and expression of target genes. A number of studies have reported pleiotropic effects of TET2 on hematopoietic stem cell self‐renewal, hematopoietic differentiation, genome instability and inflammatory response. Recent single‐cell genomics studies have identified gene promoters as well as transcription factor binding sites as TET2‐targeted genetic loci in which disruption of DNA methylation can fundamentally modify hematopoietic differentiation and promote leukemogenesis. TET2 mutations show convergent cooperativity with other disease alleles in signaling molecules, epigenetic modifiers, and spliceosome factors in hematopoietic transformation. Future studies focusing on the molecular basis of stem cell and immune regulation by TET2 loss will further deepen our understanding of the entire landscape of pathophysiology and molecular vulnerabilities of TET2‐mutated hematological malignancies.
The use of digital media: To support and enhance vulnerable children’s perspectives, voices and choices
Authors: Koch Anette Boye , Brandt Erika Zimmer
Published: October 2020

The article reports findings from a study that explored the potential of digital media to create new possibilities for professional caregivers to encounter 10 vulnerable children (7–17 years old) as subjects (rather than objects) and participants in their own lives. Five professionals received training in media pedagogy and experimented with new ways to communicate with children. Digital communication was found to expand the children's ability to engage in dialogue. Professionals need to find the courage to engage in digital communication on a child's terms as it helps generate a relationship that offers children new opportunities for raising their voices.
A meta‐analysis of anthropogenic impacts on physiological stress in wild primates
Authors: Kaisin Olivier , Fuzessy Lisieux , Poncin Pascal , Brotcorne Fany , Culot Laurence
Published: October 2020

As humanity continues to alter the environment extensively, comprehending the effect of anthropogenic disturbances on the health, survival, and fitness of wildlife is a crucial question for conservation science. Many primate populations occupy suboptimal habitats prone to diverse anthropogenic disturbances that may be sources of acute and chronic stress. Quantification of glucocorticoid (GC) concentrations has repeatedly been used to explore the impact of disturbances on physiological stress. Although it is still debated, prolonged elevation of GC levels may impair reproduction, growth, and immune system activity of individuals. We quantified the effect of anthropogenic disturbances on physiological stress in primates with a global meta‐analysis based on data from 26 articles, covering 24 distinct species in 13 different countries. Anthropogenic disturbances were classified into 6 distinct categories: habitat loss, habitat degradation, ongoing logging, hunting, tourism, and other human activities. We calculated effect sizes (Hedges’ g) with the standardized mean difference in GC concentrations between primates affected by human activity and their undisturbed conspecifics. We ran random‐effects models and subgroup analyses to estimate the overall effect as well as a cumulative effect size for each disturbance category. Overall, primates inhabiting sites subject to anthropogenic disturbances exhibited significantly higher GC levels (g = 0.60; 95% CI: 0.28–0.93). Habitat loss and hunting were overall associated with increased GC concentrations, whereas the cumulative effects of the other disturbances were not statistically significant. Biologically, high GC levels may increase fitness by enabling individuals to overcome the challenges linked to anthropogenic disturbances. However, primates in disturbed environments may have sustained elevated GC levels. To strengthen future research, it is necessary to control confounding factors systematically (e.g., diet, reproductive status, predatory pressure, and resource availability) and improve understanding of the link between GC levels and the health, fitness, and survival of animals.