bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodiversity policy beyond economic growth
Authors: Otero Iago , Farrell Katharine N. , Pueyo Salvador , Kallis Giorgos , Kehoe Laura , Haberl Helmut , Plutzar Christoph , Hobson Peter , García‐Márquez Jaime , Rodríguez‐Labajos Beatriz , Martin Jean‐Louis , Erb Karl‐Heinz , Schindler Stefan , Nielsen Jonas , Skorin Teuta , Settele Josef , Essl Franz , Gómez‐Baggethun Erik , Brotons Lluís , Rabitsch Wolfgang , Schneider François , Pe'er Guy
Published: April 2020

Increasing evidence—synthesized in this paper—shows that economic growth contributes to biodiversity loss via greater resource consumption and higher emissions. Nonetheless, a review of international biodiversity and sustainability policies shows that the majority advocate economic growth. Since improvements in resource use efficiency have so far not allowed for absolute global reductions in resource use and pollution, we question the support for economic growth in these policies, where inadequate attention is paid to the question of how growth can be decoupled from biodiversity loss. Drawing on the literature about alternatives to economic growth, we explore this contradiction and suggest ways forward to halt global biodiversity decline. These include policy proposals to move beyond the growth paradigm while enhancing overall prosperity, which can be implemented by combining top‐down and bottom‐up governance across scales. Finally, we call the attention of researchers and policy makers to two immediate steps: acknowledge the conflict between economic growth and biodiversity conservation in future policies; and explore socioeconomic trajectories beyond economic growth in the next generation of biodiversity scenarios.
Cutaneous composite lymphoma of mycosis fungoides and Hodgkin lymphoma: Response to sequential therapy
Authors: Chen Yudi , Nong Lin , Li Xin , Wang Yang
Published: April 2020

Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphoma clones that occur in the same tissue site. The occurrence of cutaneous composite lymphoma (CCL) is extremely rare. Here we report a unique case of CCL consisting of Hodgkin lymphoma (HL) and mycosis fungoides (MF). Our patient presented with longstanding erythematous plaques on the skin and later developed axillary lymph node enlargement. Histopathologically, the skin lesions were characterized by a dense dermal lymphocytic infiltrate with prominent epidermotropism of pleomorphic T‐cells, consistent with typical MF. Nonetheless, scattered large atypical cells resembling Reed‐Sternberg (R‐S) cells were interspersed among these atypical T‐cells in the deep dermis. Immunophenotyping suggested a HL origin of these R‐S cells. Monoclonality of T‐cell receptor beta gene was detected in the skin, monoclonal immunoglobulin heavy chain gene rearrangement was identified in these R‐S cells microdissected from the deep dermis, confirming the origin from HL. The lymph node biopsy showed nodular sclerosis classic Hodgkin lymphoma. Therefore, CCL of HL and MF, with lymph node HL was diagnosed. The lesions of this patient responded to a sequential treatment to HL and MF. Being aware of this rare CCL facilitates correct diagnosis and proper clinical management.
‘In This Profession We Eat Dust’: Informal and Formal Solidarity among Women Urban Transportation Workers in Nepal
Authors: Grossman‐Thompson Barbara
Published: April 2020

This article considers the working lives of women who drive electric rickshaws, known as tempos, in Kathmandu, Nepal. Drawing on ethnographic fieldwork, the author examines drivers’ precarious working conditions and the strategies they use in an effort to secure better conditions and job security. This case study illuminates the particulars of women tempo drivers’ day‐to‐day experiences and also speaks to larger debates in feminist political economy surrounding women's entrance into the paid labour force, especially in South Asia. Women drivers provide a compelling example of how socio‐economically disadvantaged women in industrializing and urbanizing cities of the global South find ways to create and protect spaces of dignified work and worker solidarity despite myriad challenges. Evidence from the research suggests that both informal and more formalized coping and resistance strategies are important mechanisms through which women seek to change the terms of their labour.
Neutrophil recruitment and intracellular vesicle transport: A short overview
Authors: Masgrau‐Alsina Sergi , Sperandio Markus , Rohwedder Ina
Published: April 2020

Recruitment of neutrophils from the intravascular compartment into injured tissue is an essential component of the inflammatory response. It involves intracellular trafficking of vesicles within neutrophils and endothelial cells, both containing numerous proteins that have to be distributed in a tightly controlled and precise spatiotemporal fashion during the recruitment process. Rab proteins, a family of small GTPases, together with their effectors, are the key players in guiding and regulating the intracellular vesicle trafficking machinery during neutrophil recruitment. This review will provide a short overview on this process and highlight new findings as well as current controversies in the field.
Normal regression of the internal umbilical remnant structures in Standardbred foals
Authors: McCoy Annette M. , Lopp Christine T. , Kooy Sarah , Migliorisi Alessandro C. , Austin Scott M. , Wilkins Pamela A.
Published: April 2020

Background

Diseases affecting the internal umbilical remnant are common in foals. Ultrasound is used to diagnose abnormalities of these structures, and to monitor treatment. However, little is known about the progression of normal internal umbilical remnant regression.

Objectives

To document normal regression of the umbilical remnant in foals over the first 6 weeks of life.

Study design

Prospective, longitudinal cohort study.

Methods

Weekly ultrasound examinations were performed beginning at 1 day of age in 34 healthy Standardbred foals. The umbilical vein was measured in cross section just cranial to the external umbilicus, at the level of the liver and midway between these points. The umbilical arteries were measured in cross section just caudal to the external umbilicus, at the apex of the bladder and at the midpoint of the bladder. The urachus was imaged longitudinally as it exited the bladder. Reduction in size over time was evaluated as percentage change in diameter.

Results

Structure diameter decreased linearly over time. The largest measurements were at 24 hours of age with a median umbilical vein diameter of 0.83 cm (IQR 0.77‐1.02 cm), median umbilical artery diameter of 0.61 cm (IQR 0.56‐0.70 cm) and median urachal diameter of 1.07 cm (IQR 1.02‐1.14 cm). There was a significant reduction in diameter for all structures (16.0%‐21.9%; corrected P < .001) within the first week of life.

Main limitations

All foals were of a single breed, and examinations and measurements were performed by multiple individuals.

Conclusions

The internal umbilical remnants (umbilical vein/arteries, and urachus) rapidly regress over the first few weeks of life. The median internal umbilical remnant diameters reported here are smaller than previously reported values, emphasising the importance of accounting for age when diagnosing umbilical abnormalities. In a healthy Standardbred foal, normal structures are difficult to definitively identify via transcutaneous ultrasound by 5‐6 weeks of age.
A machine learning approach for imputation and anomaly detection in IoT environment
Authors: Vangipuram Radhakrishna , Gunupudi Rajesh Kumar , Puligadda Veereswara Kumar , Vinjamuri Janaki
Published: April 2020

The problem of anomaly and attack detection in IoT environment is one of the prime challenges in the domain of internet of things that requires an immediate concern. For example, anomalies and attacks in IoT environment such as scan, malicious operation, denial of service, spying, data type probing, wrong setup, malicious control can lead to failure of an IoT system. Datasets generated in an IoT environment usually have missing values. The presence of missing values makes the classifier unsuitable for classification task. This article introduces (a) a novel imputation technique for imputation of missing data values (b) a classifier which is based on feature transformation to perform classification (c) imputation measure for similarity computation between any two instances that can also be used as similarity measure. The performance of proposed classifier is studied by using imputed datasets obtained through applying Kmeans, F‐Kmeans and proposed imputation methods. Experiments are also conducted by applying existing and proposed classifiers on the imputed dataset obtained using proposed imputation technique. For experimental study in this article, we have used an open source dataset named distributed smart space orchestration system publicly available from Kaggle. Experiment results obtained are also validated using Wilcoxon non‐parametric statistical test. It is proved that the performance of proposed approach is better when compared to existing classifiers when the imputation process is performed using F‐Kmeans and K‐Means imputation techniques. It is also observed that accuracies for attack classes scan, malicious operation, denial of service, spying, data type probing, wrong setup are 100% while it is 99% for malicious control attack class when the proposed imputation and classification technique are applied.
Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple‐negative breast cancer: Caspase, ΔΨm, and pro‐apoptotic gene involvement
Authors: Rosas‐González Vida Celeste , Téllez‐Bañuelos Martha Cecilia , Hernández‐Flores Georgina , Bravo‐Cuellar Alejandro , Aguilar-Lemarroy Adriana , Jave‐Suárez Luis Felipe , Haramati Jesse , Solorzano‐Ibarra Fabiola , Ortiz‐Lazareno Pablo Cesar
Published: April 2020

Breast cancer is the most frequent cancer in women worldwide, and drug resistance is common in all breast cancer types. The combination of natural products with chemotherapies has attracted attention, as it was found that natural compounds enhance the effects of standard cancer chemotherapeutic drugs and protect from side effects. Into the different natural products, garlic has been recognized for its antitumor properties. It is suggested that its anticancer effects are associated with its organo‐sulfur compounds, especially alliin and allicin. Here, we evaluated the effects of both molecules on cell death, senescence, and their senolytic potential in luminal A and triple‐negative breast cancer cells. MCF‐7 (luminal A) and HCC‐70 (triple‐negative) cells were cultured and treated with different concentrations of alliin or allicin. Then, cell viability was determined using the WST‐1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; ΔΨm was assessed using a JC‐10 fluorometric assay kit. Apoptosis‐related genes were evaluated by RT‐PCR. Proliferation was measured using bromodeoxyuridine incorporation. We also evaluated clonogenicity, senescence (β‐Galactosidase Staining), and the senolytic effect of the compounds. Our results showed that allicin has antiproliferative, anticlonogenic, and senolytic effects. In addition, allicin decreased cell viability and induced apoptosis by loss of ΔΨm, caspase‐3, caspase‐8, and caspase‐9 activation, upregulation of NOXA, P21, and BAK, as well as downregulation of BCL‐XL expression. Contrary to allicin, alliin promoted clonogenicity, induced senescence, and did not exhibit pro‐apoptotic effects in breast cancer cells.
Are potentially inappropriate and anticholinergic medications being prescribed for institutionalized elderly subjects?
Authors: Bourrel Claire , Zacarin Alice , Rousseau Vanessa , Montastruc Jean‐Louis , Bagheri Haleh
Published: April 2020

The PAAPI project (Optimising Inappropriate Prescriptions in the Elderly) is a multi‐disciplinary approach put in place by the Toulouse Pharmacovigilance Centre (CRPV) in order to improve drug prescribing practice in nursing homes. The aim of this study was to analyse the association between polypharmacy, frequency of prescriptions for potentially inappropriate medications (PIMs) and the anticholinergic burden of prescriptions in elderly patients from the PAAPI cohort. We carried out a retrospective study on residents of 24 nursing homes (EHPAD) participating in the PAAPI programme between 1er January 2017 and 31 December. Resident’s Data were collected in a single review in a random day. Drug prescriptions were analysed quantitatively and qualitatively. PIMs and anticholinergic drugs were identified by the list EU(7)PIM and the Duran scale, respectively. The total anticholinergic burden was calculated by adding the anticholinergic scores of each drug. We classified the drugs into three categories: no anticholinergic burden (burden = 0), low anticholinergic burden (≥1 ≤ 3) or high anticholinergic burden (burden > 3). A total of 1191 residents living were included, and we analysed 8869 drug prescription lines. The average age of the residents was 87.0 ± 8.3 years, and the majority (71.5%) were female. Nearly half of the residents (49.6%, n = 67) having a prescription with a high anticholinergic burden were taking more than 9 drugs (Fisher exact test P < 0.05). All the prescriptions with more than 5 PIMs (n = 23) had an anticholinergic burden > 0, with the majority (65.2%, n = 15) having a high anticholinergic burden (Kruskal–Wallis test, P < 0.0001). In this cohort, 88% (n = 539) of prescriptions with a low anticholinergic burden and 100% (n = 135) of prescriptions with a high anticholinergic burden included at least one PIM. According to our study, the anticholinergic burden of prescriptions given to residents in the PAAPI cohort is associated with the prescription of PIMs and with polypharmacy. Optimizing the use of medicines remains essential in this population, given the harmful properties of these drugs. It would also be useful for the list of anticholinergic drugs to be updated as new medicines come onto the market.
Tailoring the immune response to the availability of nutrients
Authors: Cattenoz Pierre B. , Giangrande Angela
Published: April 2020

The development and the maintenance of an efficient immune system represents a considerable metabolic investment for the organism. Ramond et al. have characterized a new molecular and cellular pathway, inhibiting the immune system in poor diet conditions in the Drosophila larva. Low nutrient conditions lead to the secretion of the adipokine NimB5 by the fat body, which inhibits the proliferation of the immune cells, hence preventing the exhaustion of the resources.
Crystal plasticity finite‐element modelling of cyclic deformation and crack initiation in a nickel‐based single‐crystal superalloy under low‐cycle fatigue
Authors: Zhang Lu , Zhao Liguo , Jiang Rong , Bullough Chris
Published: April 2020

Nickel‐based single‐crystal superalloys are predominantly used for turbine blades in aircraft engines and land‐based gas turbines. Understanding and predicting the fatigue failure of Ni‐based single‐crystal superalloys are critical to ensure the safety of these components during operation. In this paper, low‐cycle fatigue experiments were carried out to investigate cyclic deformation of a nickel‐based single‐crystal superalloy MD2, recently developed by GE Power, with different crystallographic orientations. Specialty in situ scanning electron microscope (SEM) tests were also conducted to study the slip‐controlled initiation of short cracks under low‐cycle fatigue. In particular, the stress–strain response for both [001] and [111] orientations was used to calibrate a crystal plasticity model, which allowed us to simulate the activation of crystallographic slip systems and predict the initiation of short fatigue crack. Using the accumulated shear strain as a criterion, the simulations confirmed that the slip system with the maximum accumulated shear strain appeared to control the crack initiation. The location and direction of slip traces and short cracks, captured by the crystal plasticity finite‐element simulations, agreed with the in situ SEM observations. The modelling tool will be valuable for assessing the structural integrity of critical gas turbine blades.
Ensemble projections elucidate effects of uncertainty in terrestrial nitrogen limitation on future carbon uptake
Authors: Meyerholt Johannes , Sickel Kerstin , Zaehle Sönke
Published: April 2020

The magnitude of the nitrogen (N) limitation of terrestrial carbon (C) storage over the 21st century is highly uncertain because of the complex interactions between the terrestrial C and N cycles. We use an ensemble approach to quantify and attribute process‐level uncertainty in C‐cycle projections by analysing a 30‐member ensemble representing published alternative representations of key N cycle processes (stoichiometry, biological nitrogen fixation (BNF) and ecosystem N losses) within the framework of one terrestrial biosphere model. Despite large differences in the simulated present‐day N cycle, primarily affecting simulated productivity north of 40°N, ensemble members generally conform with global C‐cycle benchmarks for present‐day conditions. Ensemble projections for two representative concentration pathways (RCP 2.6 and RCP 8.5) show that the increase in land C storage due to CO2fertilization is reduced by 24 ± 15% due to N constraints, whereas terrestrial C losses associated with climate change are attenuated by 19 ± 20%. As a result, N cycling reduces projected land C uptake for the years 2006–2099 by 19% (37% decrease to 3% increase) for RCP 2.6, and by 21% (40% decrease to 9% increase) for RCP 8.5. Most of the ensemble spread results from uncertainty in temperate and boreal forests, and is dominated by uncertainty in BNF (10% decrease to 50% increase for RCP 2.6, 5% decrease to 100% increase for RCP 8.5). However, choices about the flexibility of ecosystem C:N ratios and processes controlling ecosystem N losses regionally also play important roles. The findings of this study demonstrate clearly the need for an ensemble approach to quantify likely future terrestrial C–N cycle trajectories. Present‐day C‐cycle observations only weakly constrain the future ensemble spread, highlighting the need for better observational constraints on large‐scale N cycling, and N cycle process responses to global change.
The greening of the Northern Great Plains and its biogeochemical precursors
Authors: Brookshire E. N. Jack , Stoy Paul C. , Currey Bryce , Finney Bruce
Published: April 2020

Vegetation greenness has increased across much of the global land surface over recent decades. This trend is projected to continue—particularly in northern latitudes—but future greening may be constrained by nutrient availability needed for plant carbon (C) assimilation in response to CO2enrichment (eCO2). eCO2impacts foliar chemistry and function, yet the relative strengths of these effects versus climate in driving patterns of vegetative greening remain uncertain. Here we combine satellite measurements of greening with a 135 year record of plant C and nitrogen (N) concentrations and stable isotope ratios (δ13C and δ15N) in the Northern Great Plains (NGP) of North America to examine N constraints on greening. We document significant greening over the past two decades with the highest proportional increases in net greening occurring in the dries and warmest areas. In contrast to the climate dependency of greening, we find spatially uniform increases in leaf‐level intercellular CO2and intrinsic water use efficiency that track rising atmospheric CO2. Despite large spatial variation in greening, we find sustained and climate‐independent declines in foliar N over the last century. Parallel declines in foliar δ15N and increases in C:N ratios point to diminished N availability as the likely cause. The simultaneous increase in greening and decline in foliar N across our study area points to increased N use efficiency (NUE) over the last two decades. However, our results suggest that plant NUE responses are likely insufficient to sustain observed greening trends in NGP grasslands in the future.
Improved β‐diversity estimators based on multiple‐site dissimilarity: Distinguishing the sample from the population
Authors: Fortin Mathieu , Kondratyeva Anna , Van Couwenberghe Rosalinde
Published: April 2020

Aim

β‐diversity is often measured through incidence‐based dissimilarity indices, such as the Simpson and Sørensen indices. Multiple‐site versions of these indices, which have been recently developed, enhance the accountability of global heterogeneity relative to the original formulations. However, they are known to be sensitive to the number of sites, which hinders the comparison of β‐diversity between two populations of unequal sizes. Moreover, the populations are never completely measured and the dissimilarity must be estimated from a sample of sites.

Innovation

In this study, we propose adapted multiple‐site versions of the Simpson, Sørensen and nestedness indices that are population size‐independent as well as estimators of these indices. The properties of the indices and their estimators were tested through simulation studies. These simulation studies show that the adapted indices were population size‐independent. The estimators and their estimated standard errors were nearly unbiased for moderate sample sizes (n ≥ 25).

Main conclusions

These estimators of these adapted multiple‐site dissimilarity indices now make it possible to compare the β‐diversity of two populations of unequal sizes.
Environment resilience and public health: Assessing healthcare's vulnerability to climate change in the San Francisco Bay Area
Authors: Chen Tingting , Radke John D. , Lang Wei , Li Xun
Published: April 2020

This study investigated the vulnerability of people's health to the impact of climate change on healthcare accessibility in the San Francisco Bay Area. The study developed spatial analysis models in ArcGIS with a high‐resolution elevation data set (1 m raster base map) and summarized the scenario assessments of the associations between healthcare and the populations vulnerable to the effects of climate change. The results reveal that 34.3% of low‐income households could reach hospitals in the baseline scenario. In the peak water level (PWL) (140) scenario, 33.3% of low‐income households were within 30 min of the nearest hospital. In the baseline scenario, hospitals were accessible to 35.9% of the general population, whereas in the PWL (140) scenario the percentage was slightly lower, with 35.1% having access to hospitals. Healthcare reform increased the accessibility of hospitals to low‐income households, and these populations had equal access in the PWL (140) scenario. However, access to healthcare is controlled by distance and other variables, including income, insurance, spatial distribution, and transportation mobility. The findings and implications of this study address the explicit recognition in strategic planning of the effects of climate change in adopting policies to benefit health in the future.
Helicobacter pylori “Test‐and‐Treat” strategy with urea breath test: A cost‐effective strategy for the management of dyspepsia and the prevention of ulcer and gastric cancer in Spain—Results of the Hp‐Breath initiative
Authors: Beresniak Ariel , Malfertheiner Peter , Franceschi Francesco , Liebaert Francois , Salhi Hocine , Gisbert Javier P.
Published: April 2020

Background

Data from clinical trials comparing Helicobacter pylori (H. pylori) management strategies in patients with dyspepsia are limited. Cost‐effectiveness simulation models might help to identify the optimal strategy.

Objective

To assess the cost‐effectiveness of the H. pylori "Test and Treat" (T&T) strategy including the use of urea breath test (UBT) vs symptomatic treatment (ST) and vs upper gastrointestinal endoscopy (UGE) as a first procedure in patients with dyspepsia.

Methods

Three main strategies: “T&T” strategy including the use of UBT, "UGE" and "ST" have been compared using cost‐effectiveness models developed in accordance with the Spanish medical practice. For the model simulations, a time horizon of 4 weeks was considered for the endpoint "Dyspepsia symptoms relief" and 10 years when using "Peptic ulcer avoided" and "Gastric cancer avoided" endpoints.

Results

For the endpoint "Dyspepsia symptoms relief", T&T strategy appears to be the most cost‐effective (883€/success) compared to UGE strategy and to ST strategy (respectively 1628€ and 990€/success). For the endpoint "Probability of peptic ulcer", the T&T strategy appears to be the most cost‐effective (421€/peptic ulcer avoided/y) compared to UGE strategy and ST strategy (respectively 728€ and 632€/peptic ulcer avoided/y). For the endpoint "Gastric cancer avoided", the T&T strategy appears to be the most cost‐effective (524€/gastric cancer avoided/y) compared to UGE strategy and "ST" strategy (respectively 716€ and 696€/gastric cancer avoided/y).

Conclusions

T&T strategy including the use of UBT is the most cost‐effective medical approach for management of dyspepsia and for the prevention of ulcer and gastric cancer.
Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial
Authors: Delahunt Brett , Murray Judith D , Steigler Allison , Atkinson Chris , Christie David , Duchesne Gillian , Egevad Lars , Joseph David , Matthews John , Oldmeadow Christopher , Samaratunga Hemamali , Spry Nigel A , Srigley John R , Hondermarck Hubert , Denham James W
Published: April 2020

Aims

Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10 years outcome data from the TROG 03.04 RADAR trial.

Methods

Diagnostic prostate biopsies from 976 patients were reviewed and the presence of PNI noted. Patients were followed for 10 years according to the trial protocol or until death. The primary endpoint for the study was time to bone metastasis. Secondary endpoints included time to soft tissue metastasis, transition to castration resistance, prostate cancer‐specific mortality and all‐cause mortality.

Results

PNI was detected in 449 cases (46%), with 234 cases (24%) having PNI in more than one core. The presence of PNI was significantly associated with higher ISUP grade, clinical T staging category, National Comprehensive Cancer Network risk group, and percent positive biopsy cores. The cumulative probability of bone metastases according to PNI status was significant over the 10 years follow‐up interval of the study (log‐rank test P < 0.0001). PNI was associated with all endpoints on univariable analysis. After adjusting for baseline clinicopathological and treatment factors, bone metastasis was the only endpoint in which PNI retained its prognostic significance (hazard ratio 1.42, 95% confidence interval 1.05–1.92, P = 0.021).

Conclusions

The association between PNI and the development of bone metastases supports the inclusion of this parameter as a component of the routine histology report. Further this association suggests that evaluation of PNI may assist in selecting those patients who should be monitored more closely during follow‐up.
Impact on colorectal cancer pathology reporting practice of migration from TNM 5 to TNM 8
Authors: Loughrey Maurice B , Kent Olivia , Moore Michelle , Coghlin Caroline , Kelly Paul , McVeigh Gerard , Coleman Helen G
Published: April 2020

Aims

The introduction of TNM 8 into UK pathology practice in January 2018 considers tumour deposits in colorectal cancer staging for the first time. The impact of this new classification on pathology reporting practices has yet to be evaluated.

Methods and results

A clinical audit was conducted, comparing consecutive colorectal cancer resection specimens reported under TNM 5 classification guidelines in 2017 (n = 177) and TNM 8 guidelines in 2018 (n = 234). Tumour features (venous invasion, perineural invasion, lymph node metastatic disease, tumour deposits) and changes in reporting practices were evaluated among four specialist gastrointestinal pathologists working within a large pathology department. Adoption of TNM 8 practice led to an approximate doubling in the use of ancillary stains (41.0% of TNM 8 versus 22.0% of TNM 5 cases, P < 0.001) to help evaluate tumours. A narrowing of the range between pathologists was observed in reporting cases as having one or more form of regional, extramural, discontinuous tumour (TNM 5 range = 50.0–79.0%, TNM 8 range = 57.8–65.7%), with no change in the overall proportion of cases reported as such (62.7% versus 62.4%, P = 0.95). However, significant interobserver variation in reporting rates for individual parameters remained.

Conclusion

TNM 8 colorectal cancer staging offers potentially greater reproducibility in pathology reporting of regional, extramural, discontinuous disease with similar proportions of patients reported as having one or more of these forms of tumour spread compared with TNM 5. Further guidance in defining individual features is required to reduce interobserver variation in pathology assessments and to help elucidate the clinical significance of each parameter.
Understanding the mechanisms that facilitate specificity, not redundancy, of chemokine‐mediated leukocyte recruitment
Authors: Dyer Douglas P.
Published: April 2020

Chemokines (chemotactic cytokines) and their receptors are critical to recruitment and positioning of cells during development and the immune response. The chemokine system has long been described as redundant for a number of reasons, where multiple chemokine ligands can bind to multiple receptors and vice versa. This apparent redundancy has been thought to be a major reason for the failure of drugs targeting chemokines during inflammatory disease. We are now beginning to understand that chemokine biology is in fact based around a high degree of specificity, where each chemokine and receptor plays a particular role in the immune response. This specificity hypothesis is supported by a number of recent studies designed to address this problem. This review will detail these studies and the mechanisms that produce this specificity of function with an emphasis on the emerging role of chemokine–glycosaminoglycan interactions.
“If we do not look for it, we do not see it”: Clinicians' experiences and understanding of identifying post‐traumatic stress disorder in adults with autism and intellectual disability
Authors: Kildahl Arvid Nikolai , Helverschou Sissel Berge , Bakken Trine Lise , Oddli Hanne Weie
Published: April 2020

Background

Individuals with autism spectrum disorder (ASD) and intellectual disability (ID) are at increased risk of potentially traumatic events and may be at increased risk of post‐traumatic stress disorder (PTSD). However, knowledge regarding identification of PTSD in this population is limited. The aim of this study was to investigate clinical experience regarding PTSD and trauma assessment in individuals with co‐occurring ASD and ID.

Method

Interpretative phenomenological analysis was used to explore experiences of identifying PTSD in this population among 18 mental health clinicians working with ASD and ID.

Results

Informants viewed PTSD in individuals with ASD and ID as equivalent to PTSD in the general population, but with causes and expressions potentially differing. Several factors were described to contribute to challenges in identification.

Conclusions

Trauma may have severe impact in individuals with ASD and ID. Multidimensional, individualized assessment strategies seem necessary to recognize PTSD or trauma‐related symptoms in this population.
ENO1‐targeted superparamagnetic iron oxide nanoparticles for detecting pancreatic cancer by magnetic resonance imaging
Authors: Wang Lei , Yin Hang , Bi Rongrong , Gao Guo , Li Kaicheng , Liu Hai‐Lin
Published: April 2020

The aim of this study was to investigate in vitro magnetic resonance imaging (MRI) of PDAC using ENO1‐targeted superparamagnetic iron oxide nanoparticles and xenograft models. Expression level and location of ENO1 protein in pancreatic cancer cell lines of CFPAC‐1 and MiaPaCa‐2 were detected by Western blotting, flow cytometry and confocal microscopy. Dex‐g‐PCL/SPIO nanoparticles targeting ENO1 were constructed with ENO1 antibody and characterized by MRI. In addition, ENO1‐Dex‐g‐PCL/SPIO nanoparticles were tested to assess their efficacy on the detection of PDAC using in vitro and in vivo MRI. The results showed that ENO1 was expressed in both human PDAC cell lines of CFPAC‐1 and MiaPaCa‐2, demonstrating that the localization of cytoplasm and membrane was dominant. It was confirmed that ENO1 antibody was connected to the SPIO surface in ENO1‐Dex‐g‐PCL/SPIO nanoparticles. The nanoparticles had satisfactory superparamagnetism and significantly enhance the detection of PDAC by in vivo and in vitro MRI. In conclusion, ENO1 can serve as a membrane protein expressed on human PDAC cell lines. ENO1‐targeted SPIO nanoparticles using ENO1 antibody can increase the efficiency of detection of PDAC by in vitro and in vivo MRI.
Safety in moderate‐to‐severe plaque psoriasis patients with latent tuberculosis treated with guselkumab and anti‐tuberculosis treatments concomitantly: results from pooled phase 3 VOYAGE 1 & VOYAGE 2 trials
Authors: Puig L. , Tsai T.‐F. , Bhutani T. , Uy J. , Ramachandran P. , Song M. , You Y. , Gooderham M. , Lebwohl M.
Published: April 2020

Background

Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new‐onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)‐23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics.

Objectives

Safety in moderate‐to‐severe psoriasis patients with LTBI treated with guselkumab (IL‐23 inhibitor) and LTBI treatment was evaluated.

Methods

In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo → guselkumab crossover occurred at week 16 and adalimumab → guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab‐treated patients receiving and not receiving LTBI treatment.

Results

At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab‐treated patients without LTBI (LTBI−) through week 100. Two cases of active TB occurred in LTBI− patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI− patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI− patients.

Conclusions

No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long‐term treatment with guselkumab was generally well‐tolerated through up to 2 years in patients receiving LTBI medications.
Parkinson’s disease and skin cancer risk: a nationwide population‐based cohort study in Korea
Authors: Ryu H.J. , Park J.‐H. , Choi M. , Jung J.‐H. , Han K. , Kwon D.‐Y. , Kim D.‐H. , Park Y.‐G.
Published: April 2020

Background

Previous studies have reported that patients with Parkinson’s disease (PD) have a significantly lower risk of cancer. Studies reporting prevalence of skin cancers in Parkinson’s disease mostly involve Caucasians.

Objective

A nationwide population‐based study was conducted to determine the risk of skin cancer in patients diagnosed with PD in Korea.

Methods

Data obtained from National Health Insurance Claims records were used to retrieve information about 70 780 patients with newly diagnosed PD between January 2010 and December 2015. The control group included 353 900 sex‐ and age‐matched patients without PD. In this nationwide population‐based cohort study, we investigated the association between PD and skin cancer.

Results

The overall hazard ratio (HR) of skin cancers in patients with PD was 1.169 (95% CI, 1.005–1.359) compared with non‐PD group. Among patients with PD, males aged above 65 had a 2.8‐fold increase in the risk for melanoma development than the non‐PD group (HR, 2.825; 95% CI, 1.395–5.721). In addition, female PD patients aged above 65 years showed a 1.3‐fold increase in non‐melanoma skin cancer risk than the non‐PD group (HR, 1.305; 95% 1.073–1.589).

Conclusion

Compared with the general population, Korean patients diagnosed with PD had a greater risk of skin cancer. Especially, male patients aged 65 years and above, and diagnosed with PD had a significant risk of melanoma development compared with control.
Irrigation technology and water rebound in China's agricultural sector
Authors: Fang Lin , Wu Fengping , Yu Yantuan , Zhang Lin
Published: April 2020

By using the data of 30 provinces from 1998 to 2016 in China, this paper estimates the water rebound effect in the agricultural crop farming by combining Slacks‐based Measure (SBM‐based) of Malmquist Index and Logarithmic Mean Divisia Index (LMDI) method. We find that the average water rebound effect is 70.3%, implying that over two‐thirds of the water saving from irrigation technology improvement is offset by higher water consumption. We find evidence on the regional heterogeneity in terms of the magnitude of rebound: Southwest is the highest, whereas Northwest is the lowest. The heterogeneous rebound effect across regions is mainly due to the difference in water endowment and irrigation land availability. Our results indicate that irrigation technology improvement is not necessarily sufficient for achieving agricultural water conservation. In particular, the difference in natural geography conditions across regions needs to be considered in designing water conservation policies at a sub‐regional level.
Real‐Time Pricing and Imperfect Competition in Electricity Markets*
Authors: Poletti Stephen , Wright Julian
Published: April 2020

We analyze the effects of the adoption of real‐time pricing (RTP) of electricity when generating firms have market power. We find that an increase in consumers on RTP contracts decreases peak prices and increases off‐peak prices, increases consumer surplus (both for switching and non‐switching consumers) and welfare, while decreasing industry profits, with these effects being magnified by the extent of market power. We illustrate these results by calibrating our model to the New Zealand electricity market, and find that taking into account the market power of generating firms increases the efficiency gains from RTP adoption by 41%.
An innovative individual‐level caries severity and progression indicator among children
Authors: Lim Sungwoo , Alqahtani Saad , Tellez Marisol , Ismail Amid I.
Published: April 2020

Objective

To propose an individual‐level indicator of caries severity based on the maximum score generated using the international caries detection and assessment system (ICDAS) and test validity of this individual‐level indicator by assessing differences between this proposed indicator and the traditional decayed, missing, and filled surfaces (DMFS or dmfs for primary teeth) index.

Methods

Data on caries severity were collected using a representative sample of children from Detroit, Michigan, aged less than 6 years (N = 749) examined in 2002–2003 (W1) and 2004–2005 (W2). For each wave, each child was assigned to six caries severity groups based on the maximum ICDAS scores. This individual‐level indicator was then compared with the surface‐level dental caries measure (dmfs + DMFS). In addition, caries progression between W1 and W2 were assessed using individual‐level and tooth surface‐level indicators.

Results

Both measures were linearly related, and the relationship was statistically significant (P < 0.001).

Conclusion

An individual‐level caries progression indicator can be developed that is simple and has the ability to communicate with policymakers and the public the severity and impact of dental caries and it can add value to the conventional presentation of DMF/dmf data.
Paulinella, a model for understanding plastid primary endosymbiosis
Authors: Gabr Arwa , Grossman Arthur R. , Bhattacharya Debashish
Published: April 2020

The uptake and conversion of a free‐living cyanobacterium into a photosynthetic organelle by the single‐celled Archaeplastida ancestor helped transform the biosphere from low to high oxygen. There are two documented, independent cases of plastid primary endosymbiosis. The first is the well‐studied instance in Archaeplastida that occurred ca. 1.6 billion years ago, whereas the second occurred 90–140 million years ago, establishing a permanent photosynthetic compartment (the chromatophore) in amoebae in the genus Paulinella. Here, we briefly summarize knowledge about plastid origin in the Archaeplastida and then focus on Paulinella. In particular, we describe features of the Paulinella chromatophore that make it a model for examining earlier events in the evolution of photosynthetic organelles. Our review stresses recently gained insights into the evolution of chromatophore and nuclear encoded DNA sequences in Paulinella, metabolic connectivity between the endosymbiont and cytoplasm, and systems that target proteins into the chromatophore. We also describe future work with Paulinella, and the potential rewards and challenges associated with developing further this model system.
Maternal perinatal depression and infant sleep problems at 1 year of age: Subjective and actigraphy data from a population‐based birth cohort study
Authors: Halal Camila S. , Bassani Diego G. , Santos Iná S. , Tovo‐Rodrigues Luciana , Del‐Ponte Bianca , Silveira Mariangela F. , Bertoldi Andréa D. , Barros Fernando C. , Nunes Magda L.
Published: April 2020

This study used data from 2,222 mothers and infants participating in a population‐based birth cohort to verify whether maternal depression in the perinatal period was associated with poor infant sleep. Mothers who scored ≥13 points on the Edinburgh Postnatal Depression Scale at 16–24 weeks of gestation and/or 3 months after delivery were considered perinatally depressed. The main outcome variable was poor infant sleep at 12 months of age, defined as >3 night wakings, nocturnal wakefulness >1 hr or total sleep duration <9 hr. Infant sleep data were obtained with the Brief Infant Sleep Questionnaire (BISQ) and 24‐hr actigraphy monitoring. Prevalence of perinatal depression in the sample was 22.3% (95% confidence interval [CI], 20.5–24.0). After Poisson regression, infants of depressed mothers showed an adjusted relative risk (RR) of 1.44 (95% CI, 1.00–2.08; p = .04) for >3 night wakings with questionnaire‐derived data. When actigraphy data were analysed, no association was found between perinatal depression and poor infant sleep (adjusted RR, 1.20; 95% CI, 0.82–1.74; p = .35). In conclusion, although mothers in the depressed group were more likely to report more night wakings, objective data from actigraphy did not replicate this finding. Dysfunctional cognition, maternal behavioural factors and sleep impairment associated with perinatal depression may affect the mother's impression of her infant's sleep.
Working for 200 Euro? The Unintended Effects of Traineeship Reform on Youth Labor Market Outcomes
Authors: Tomić Iva , Zilic Ivan
Published: April 2020

This paper evaluates the effects of an active labor market policy (ALMP) reform, the so‐called SOR measure (vocational training for work without commencing employment), on youth labor market outcomes in the newest EU member state—Croatia. In 2012, SOR was redesigned to ease the first labor market entry and promote on‐the‐job training, enabling a young person without relevant work experience to get a one‐year contract and a net monthly remuneration of 210 euro, while after 2014, the measure also became a part of the European Youth Guarantee. Pooling Croatian Labor Force Surveys from 2007 to 2016 and using the difference‐in‐difference strategy, we estimate the causal intent‐to‐treat effect of the program reform on labor market outcomes. The main results indicate that the reform has had, at best, neutral effects on employment and unemployment, while there is evidence that a portion of young individuals was propelled into inactivity. Though expected, adverse effect on wages—both at the mean and at higher percentiles of the wage distribution—is driven mostly by wages received by women and university graduates.
Population transcriptomics reveals weak parallel genetic basis in repeated marine and freshwater divergence in nine‐spined sticklebacks
Authors: Wang Yingnan , Zhao Yongxin , Wang Yu , Li Zitong , Guo Baocheng , Merilä Juha
Published: April 2020

The degree to which adaptation to similar selection pressures is underlain by parallel versus non‐parallel genetic changes is a topic of broad interest in contemporary evolutionary biology. Sticklebacks provide opportunities to characterize and compare the genetic underpinnings of repeated marine‐freshwater divergences at both intra‐ and interspecific levels. While the degree of genetic parallelism in repeated marine‐freshwater divergences has been frequently studied in the three‐spined stickleback (Gasterosteus aculeatus), much less is known about this in other stickleback species. Using a population transcriptomic approach, we identified both genetic and gene expression variations associated with marine‐freshwater divergence in the nine‐spined stickleback (Pungitius pungitius). Specifically, we used a genome‐wide association study approach, and found that ~1% of the total 173,491 identified SNPs showed marine‐freshwater ecotypic differentiation. A total of 861 genes were identified to have SNPs associated with marine‐freshwater divergence, but only 12 of these genes have also been reported as candidates associated with marine‐freshwater divergence in the three‐spined stickleback. Hence, our results indicate a low degree of interspecific genetic parallelism in marine‐freshwater divergence. Moreover, 1,578 genes in the brain and 1,050 genes in the liver were differentially expressed between marine and freshwater nine‐spined sticklebacks, ~5% of which have also been identified as candidates associated with marine‐freshwater divergence in the three‐spined stickleback. However, only few of these (e.g., CLDND1) appear to have been involved in repeated marine‐freshwater divergence in nine‐spined sticklebacks. Taken together, the results indicate a low degree of genetic parallelism in repeated marine‐freshwater divergence both at intra‐ and interspecific levels.